Virginia Bartok, RPh, MBA

Two new guidelines have many clinicians, newscasters, and patients talking.

2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8)

 has made the news for its simplified approach to hypertension (HTN) treatment. The second, the 

2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults

 is a joint effort of the American College of Cardiology (ACC) and the American Heart Association (AHA). Its recommendations—recommendations that have generated some controversy&mdash; include new advice for lipid-lowering therapy in people at high risk for cardiovascular disease (CVD). CVD is currently the leading cause of death and disability in the United States.

Clinical practice guidelines debuted in the 1970s and began to proliferate in earnest in the 1990s. In 1990, the Institute of Medicine (IOM) defined guidelines as systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances.

 Guidelines have evolved and changed over the ensuing 25 years. They have multiplied to the point that clinicians must often choose among many different (and sometimes conflicting) guidelines for certain conditions.

In 2011, the IOM issued a statement indicating, “Because of the large number of clinical practice guidelines available, practitioners and other guideline users find it challenging to determine which guidelines are of high quality.” IOM had been tasked by a 2008 Congressional mandate to develop standards for rigorous, trustworthy clinical practice guidelines. 6 IOM’s findings, 

Standards for Developing Trustworthy Clinical Practice Guidelines

, have helped many organizations refine their processes.

From the start, many clinicians grumbled about guideline complexity and the trend toward “cookbook medicine,” but as good outcomes from guided practice accumulated, acceptance increased. Additionally, guideline changes have been introduced in response to user feedback, statistician recommendations, and of course, better evidence to answer pressing clinical questions. Ideal guidelines offer concise instructions for diagnostic or screening tests; how to provide medical or surgical services; how long patients should be hospitalized; and clinical practice details.

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) issued its first recommendations concerning HTN in 1976. The professionally diverse expert panel was convened by the National Heart, Lung, and Blood Institute (NHLBI) and reconvened every 3 to 4 years. NHLBI appointed the 8th JNC panel in 2008 and charged them with answering 3 key questions that reflected clinicians’ most common concerns

 In adults with HTN, does initiating antihypertensive pharmacologic therapy at specific blood pressure (BP) thresholds improve health outcomes?

 Clinically translated to mean, “At what threshold BP should clinicians prescribe medication?

 In adults with HTN, does treatment with antihypertensive pharmacologic therapy to a specified BP goal lead to improvements in health outcomes? 

Clinically translated to mean, “At what BP do you maintain medication?

 In adults with HTN, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes? 

Clinically translated to mean, “What antihypertensive medications are preferred to reach specific patients’ goals?

 the JNC 8 team based their work on systematic literature review, but emphasized user accessibility in the final design. Concerns with 2003 JNC 7 took center stage because many primary care clinicians found that JNC 7’s BP-lowering recommendations were too aggressive. For elders in particular, treating to the 140/90 mm Hg BP goal frequently resulted in iatrogenic orthostatic hypotension and falls. JNC 7 also recommended lower BPs for patients with diabetes or chronic kidney disease (CKD).

The important take-home message for pharmacists is that JNC 8 simplifies treatment—most patients have target BPs of 140/90 mm Hg.

 The target BP for elderly is less aggressive (150/90 mm Hg) unless they tolerate treatment to lower levels (see Table 1

Of note, the guideline review process changed mid-development. NHLBI had endorsed past guidelines before publication in conjunction with professional groups. NHLBI did not endorse JNC 8 in advance, announcing in June 2013 it would stop developing clinical guidelines, including those currently under revision. Their new approach would be to partner with and support select organizations to develop guidelines.

 This controversial decision would have delayed publication of the much-anticipated JNC 8 guideline had not the authors published independently.

For JNC 8, external methodology experts reviewed and summarized randomized controlled trials. To be included, HTN studies had to have enrolled adults 18 years or older and be structured for patient-oriented outcomes. Studies that enrolled both men and women and recruited at least 100 participants were essential to reduce the probability of bias. They also targeted studies that focused on geriatrics, certain racial and ethnic groups, and smokers. Some studies included critical subgroups (eg, patients with CKD, coronary artery disease, diabetes, and previous stroke). All recommendations were made based on consensus if possible or a two-thirds majority if consensus couldn’t be achieved.

JNC 8 states its main objective unmistakably: HTN treatment must attain and maintain the patient’s BP goal. The Online Figure

 describes the process primary care providers should follow. If the patient is adherent to 3 drugs but cannot tolerate additional drugs or HTN continues, the prescriber can use antihypertensives from other classes. If this strategy fails, the prescriber may need to refer the patient to a cardiologist.

Let’s look next at the key recommendations from the November 2013 

ACC/ AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults

 This guideline was also developed by an expert panel convened by NHLBI (and completed under its auspices). NHLBI charged the panel to find the best evidence to guide treatment of blood cholesterol. Its impetus was the rising rate of atherosclerotic cardiovascular disease (ASCVD, which includes coronary heart disease, stroke, and peripheral arterial disease). The AHA and ACC assumed joint governance, management, and publication of this guideline, as they had with 4 other prevention guidelines.

This guideline differs from previous guidelines: instead of establishing specific target levels for low-density lipoprotein cholesterol (LDL-C), it identifies groups in which LDL-lowering appears to be most beneficial.

Definitions of optimal LDL cholesterol levels are unchanged. The user-friendly recommendations include a flow diagram for easy clinical application. Bright colors correspond to the strength of the recommendations.

The guideline emphasizes the importance of adopting a heart-healthy lifestyle to prevent and control hyperlipidemia and HMG-CoA reductase inhibitor (statin) therapy as secondary and primary prevention, especially in populations that have yet to develop cardiovascular pathology (see Table 2). Statins are preferred because evidence shows they provide the greatest benefit with few safety issues compared with other cholesterol-lowering drugs. However, other drugs have a cholesterol-lowering role, especially in patients intolerant to statins. The guideline defines moderate-intensity therapy as lowering LDL-C by 30% to <50%. High-intensity therapy lowers LDL-C by >50%.

Another recommendation is for clinicians to use the new Pooled Cohort Equations to estimate 10-year ASCVD risk in white and black men and women (the calculator is available at http://tinyurl .com/mjfnrn3). The guideline indicates that risk assessment tools can identify patients who may benefit from statins before blood cholesterol becomes an issue. It also describes high-risk groups that may not benefit.

The guideline also addresses and dismisses other cholesterol lowering approaches (treat to target, lowest is best, and lifetime risk, all explained thoroughly in the document). By discounting these approaches, the panel arrived at the practical, simple-to-implement “treat level of ASCVD risk” to determine the 4 statin benefit groups.

What will this mean in the pharmacy? Researchers recently determined that if applied as recommended, the new guidelines would increase the number of adult Americans recommended for statin treatment from 43.2 million to 56 million. Most would not have CVD, but rather a calculated CVD risk over the next 10 years of >7.5%. In other words, 87% of men and 53% of women aged 60 to 75 years would take statins, up from 30% and 21% respectively under the old guideline.

 Many experts object to the ASCVD calculator, calling it useful in clinical practice but flawed. In certain circumstances, a change of 1 mm Hg in a patient’s BP could increase the ASCVD lifetime risk estimation from 5% to 36%.

 Statisticians from Brigham and Women’s Hospital in Boston report that the ASCVD calculator overestimates expected (as opposed to observed) risk by 75% to 100%. In doing so, it makes roughly 30 million more Americans eligible for statin therapy.

These guidelines don’t address all patients. Patients’ unique needs should drive the target BP or cholesterol level and selection of specific drugs. Clinicians need to involve patients in discussion before initiating antihypertensive or cholesterollowering treatment. Guidelines must not replace sound clinical judgment. Every patient deserves to be treated with his or her unique clinical picture in mind.

Virginia Bartok, RPh, MBA, is a pharmacist whose primary practice was in indigent care. She currently provides case management for several geriatric patients.

		James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). 

		Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA Cholesterol Guideline Panel. Treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: synopsis of the 2013 American College of Cardiology/American Heart Association cholesterol guideline. 

		Field MJ, Lohr KN, eds. Clinical practice guidelines: directions for a new program. Washington, DC: National Academy Press; 1990.

		Kotchen TA. Developing hypertension guidelines: an evolving process. 

		Salvo M, White CM. Reconciling multiple hypertension guidelines to promote effective clinical practice. 

. 2014;48(9):1242-1248 [epub ahead of print].

		Institute of Medicine. Clinical practice guidelines we can trust. Published March 23, 2011. www.iom.edu/Reports/2011/Clinical-Practice-Guidelines-We-Can-Trust.aspx. Accessed July 10, 2014.

		Institute of Medicine. Standards for developing trustworthy clinical practice guidelines. Institute of Medicine website. March 23, 2011. www.iom.edu/Reports/2011/Clinical-Practice-Guidelines-We-Can-Trust/Standards.aspx. Accessed July 10, 2014.

		The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). www.nhlbi.nih.gov/guidelines/hypertension/. http://www.nhlbi.nih.gov/files/docs/guidelines/jnc7full.pdf. Accessed July 10, 2014.

		Gibbons GH. NHLBI adopts new collaborative partnership model for clinical practice guidelines development. www.nhlbi.nih.gov/about/directorscorner/messages/nhlbi-adopts-new-collaborative-partnership-model-for-clinical-practice-guidelines-development.html. National Institutes of Health website. June 19, 2013. Accessed July 10, 2014.

		Pencina MJ, Navar-Boggan AM, D'Agostino RB Sr, et al. Application of new cholesterol guidelines to a population-based sample. 

		Penberthy WT. More on the controversies surrounding implementation of new lipid management guidelines. 

. April 13, 2014. www.hcplive.com/conferences/2014-acp/More-on-the-Controversies-Surrounding-Implementation-of-New-Lipid-Management-Guidelines-. Accessed July 10, 2014.

		Cook NR, Ridker PM. Response to Comment on the reports of over-estimation of ASCVD risk using the 2013 AHA/ACC risk equation. 

Articles

Blood Pressure and Cholesterol: Embracing New Guidelines

Knowledge gaps regarding antiphospholipid syndrome pose challenges.

Antiphospholipid syndrome (APS) is an autoimmune disorder that causes coagulation problems. It occurs in 2 forms. The first, vascular APS, primarily causes vascular thrombosis. The second form, obstetric APS, is similar but occurs in pregnant women and can cause harm to the woman and her unborn child (Table 1). With both conditions, patients develop persistent circulating antiphospholipid antibodies (aPLs), which include anticardiolipin antibodies, anti-beta2-glycoprotein I antibodies, and/or lupus anticoagulant (LA).

Clinical thrombosis occurs when aPLs mediate the activation of platelets, monocytes, and endothelial cells. Subsequently, an inflammatory process disrupts the natural anticoagulant and fibrinolytic systems.

 Although all of the antibodies are significant, patients may not have all of them. The presence of LA is associated with the highest risk for causing both arterial thrombosis and venous thromboembolism. Patients deemed “triple positive” (possessing all 3 antibodies) are at highest risk for thrombosis and recurrent thrombosis.

APS affects roughly 0.5% of the population, with approximately 80% of cases developing in women. Only 12% of cases are diagnosed after 50 years of age, making this primarily a disease of the young.

 APS may be idiopathic (also called primary) or may occur secondary to other related disease states such as systemic lupus erythematosus and a lupus-like syndrome.

 Approximately 13% of patients with stroke, 11% with myocardial infarction, 9.5% with deep vein thrombosis, and 6% with pregnancy morbidity are positive for aPLs. Despite adequate anticoagulation, 50% to 60% of patients with APS experience a thrombotic event within 6 years. Clearly, APS causes serious health consequences.

Clinical management plans should focus on avoiding thrombotic and/or obstetric recurrences. Patients with vascular APS usually require long-term anticoagulants—management follows the process used to manage thrombotic events in the general population. If thrombosis occurs, patients receive unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) for at least 5 days. They are then switched to oral anticoagulant agents, mainly vitamin K antagonists (VKAs). Among the VKAs, warfarin is used almost exclusively.

In obstetric patients with APS, several strategies have been proposed to improve pregnancy outcomes, including combinations of low-dose aspirin and UFH or LMWH, with study results documenting improved pregnancy and live birth rates in patients managed this way. Thrombosis cannot explain all the aPL-mediated complications in obstetric APS.

 Unlike LMWH, heparin seems to prevent an aPL-related pathogenic action on the fetal side of the placenta (trophoblast cells) and also on maternal endometrial endothelial cells. Some experts prefer heparin for this reason. Among women who are treated adequately with aspirin and anticoagulants, 75% to 80% have successful pregnancies.

 Women who do not respond to aspirin and anticoagulants have limited options. Some clinicians prescribe prednisolone or intravenous immunoglobulin.

Although VKAs remain the cornerstone of long-term APS treatment, their limits— narrow therapeutic window, food and drug interactions, and highly variable patient response&mdash;are well known. VKA management in APS patients requires close monitoring of international normalized ratio (INR). Frequent blood draws and rigid food rules may affect patients’ quality of life. Additionally, some patients with APS experience INR inaccuracy; they may need a higher INR therapeutic target of 3.0 to 4.0. APS patients with LA tend to have more problems with INR than others.

 LA interferes with INR and can prolong INR at baseline (before warfarin therapy starts). For these patients, experts still cannot agree on a standard INR target range.

Patients with LA-positive APS may benefit from use of an alternative test for warfarin monitoring: the chromogenic factor X (CFX) assay. CFX is a phospholipid- independent test unaffected by the LA clotting artifact. CFX results, reported as a percentage of normal activity, are inversely related to INR values. Normal target CFX ranges from 20% to 40%, where 40% equals an INR of 2.0 and 20% equals an INR of 3.0. The drawbacks with the CFX assay are its cost, which can exceed $400 per test, and the fact that many facilities send the test to an outside laboratory, creating a 24- to 72-hour delay. LA patients who have prolonged prothrombin time values at baseline and those who test positive for LA more than once not only benefit from this test, but they absolutely need it. Patients who experience recurrent venous thromboembolism may also benefit from more accurate monitoring with CFX. Some sites use CFX with INR monitoring when initiating anticoagulation. Once the patient stabilizes, the CFX is used intermittently (eg, once for every 4 to 6 INR draws) to ensure that the CFX and INR still correlate and the originally CFX-calibrated INR goal is still therapeutic.

The newer, direct oral anticoagulants inhibit a single enzyme of the coagulation cascade. Compared with VKA, they are more pharmacokinetically and pharmacodynamically stable profiles. Prescribed as fixed doses, they have few food or drug interactions, require no laboratory monitoring, and predictably address coagulation. To date, no large phase 3 clinical trials have been completed in APS patients, but they are under way. The role of anticoagulants in APS management remains uncertain. The 14th International Congress on Antiphospholipid Antibodies Task Force Report on Catastrophic Antiphospholipid Syndrome recommends using the directacting anticoagulant only in patients with proven VKA allergy or intolerance or poor anticoagulant control.

Information is needed to fill our APS knowledge gaps. Despite decades of research, our understanding of how this condition develops remains elusive. The research community is forging ahead: The AntiPhospholipid Syndrome Alliance for Clinical Trials and International Networking group (APS ACTION) has been formed to promote research and to educate prescribers and patients. APS ACTION encourages persistently aPL-positive patients to enroll in largescale clinical trials.

 Other patient resources are listed in Table 2. As we learn and apply better information, perhaps patients with APS will be more likely to deliver healthy children and suffer fewer clot-related medical problems.

Ms. Bartok is a retired pharmacist and a professional writer. Her primary practice was in indigent care, and she currently manages a small caseload of elderly patients with chronic disease.

1. Moll S, Ortel T. Monitoring warfarin therapy in patients with lupus anticoagulants. 

2. Robert A, Le Querrec A, Delahousse B, et al. Control of oral anticoagulation in patients with the antiphospholipid syndrome: influence of the lupus anticoagulant on international normalized ratio. 

3. Willis R, Harris E, Pierangeli S. Pathogenesis of the antiphospholipid syndrome. 

4. Galli M. The antiphospholipid triangle. 

5. D'Ippolito S, Meroni PL, Koike T, Veglia M, Scambia G, Di Simone N. Obstetric antiphospholipid syndrome: a recent classification for an old defined disorder. 

. 2014;13:901-908. 6. Meroni PL, Raschi E, Grossi E, et al. Obstetric and vascular APS: same autoantibodies but different diseases? 

7. Galarza-Maldonado C, Kourilovitch MR, Perez-Fernandez OM, et al. Obstetric antiphospholipid syndrome. 

8. Cohen D, Berger S, Steup-Beekman G, Bloemenkamp K, Bajema I. Diagnosis and management of the antiphospholipid syndrome. 

9. Cervera R, Piette J, Font J, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. 

10. Gómez-Puerta JA, Cervera R. Diagnosis and classification of the antiphospholipid syndrome. 

11. Andreoli L, Chighizola CB, Banzato A, Pons-Estel GJ, Ramire de Jesus G, Erkan D. Estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis: a critical review of the literature. 

12. Girardi G, Redecha P, Salmon JE. Heparin prevents antiphospholipid antibody-induced fetal loss by inhibiting complement activation. 

13. Ziakas PD, Pavlou M, Voulgarelis M. Heparin treatment in antiphospholipid syndrome with recurrent pregnancy loss: a systematic review and meta-analysis. 

14. Ruffatti A, Tonello M, Visentin MS, et al. Risk factors for pregnancy failure in patients with anti-phospholipid syndrome treated with conventional therapies: a multicentre, case-control study. 

15. Branch W; Obstetric Task Force. Report of the Obstetric APS Task Force: 13th International Congress on Antiphospholipid Antibodies, 13th April 2010. 

16. Adcock D, Duff S. Enhanced standardization of the international normalized ratio through the use of plasma calibrants: a concise review. 

17. Crowl A, Schullo-Feulner A, Moon JY. Warfarin monitoring in antiphospholipid syndrome and lupus anticoagulant. 

18. Cervera R, Rodríguez-Pintó I, Colafrancesco S, et al. 14th International Congress on Antiphospholipid Antibodies Task Force Report on Catastrophic Antiphospholipid Syndrome. 

Antiphospholipid Syndrome: Avoiding Thrombotic and Obstetric Issues

Relief is available for common cold symptoms.

The cold virus—a human enemy that has been around for centuries&mdash;is persistent and annoying. This upper respiratory tract infection is still the same constellation of symptoms&mdash;sore throat, nasal congestion, rhinorrhea, cough, fever, and muscle aches and pains

—and to date, no cure exists. Regardless, reviewing the most common treatment algorithms can assist pharmacists in aiding the stream of bleary-eyed, sniffling customers who come to the pharmacy during cold season. Start with a review of the basics in Table 1.

	In children and adults, pharmacists usually counsel patients who present with clear symptoms. They should refer patients who have “red flag” symptoms to a physician (Online Table 2).

	Symptom relief is the main management strategy, since the common cold is viral and we have no effective treatment. Options include rest, ample hydration, antihistamines, and nasal decongestants.

 Patients may need to be reminded to disinfect their environments using phenol-alcohol—based compounds, wash their hands, avoid smoking and alcohol, elevate their heads when sleeping if it helps breathing, and humidify air to soothe nasopharyngeal mucus membranes.

	Most patients will want OTC medication for symptoms. Cold and cough medications were among the top 20 substances leading to death in children before 2008, prompting the FDA to require that manufacturers voluntarily relabel these products. Since 2008, these products have had labels that indicate they should not be used in children younger than 4 years. After the labeling change, the number of emergency department (ED) visits related to cough and cold medications (therapeutic errors, unintentional exposures, and adverse drug events) reported in children younger than 2 years halved.

 Poison control centers reported decreases in ED visits for older children also.

 An effective alternative to OTC medication for infants with congestion and obstruction is nasal saline drops with bulb-syringe nostril aspiration.

Table 2: The Common Cold: Red Flags Warranting Referral 

	·         Temperature higher than 100.4°F (30°C)

	·         Chest pain or shortness of breath

	·         Underlying chronic cardiopulmonary disease

	·         Symptoms lasting more than 10 days

	·         Age <9 months or frail patients of advanced age

	·         Serious symptoms unresponsive to OTC medicines, or new symptoms suggesting complications (eg, otitis media, sinusitis, chronic bronchitis, exacerbations of reactive airway disease)

	The Online Figure describes treatments and interventions that work. Studies of zinc sulfate show it may decrease symptom duration when it is taken within 24 hours of symptom onset; note that some patients find its taste intolerable and may experience nausea or a loss of taste or smell.

	First-generation antihistamines, topical anticholinergics, and ipratropium bromide (available by prescription) reduce rhinorrhea by 25% to 35%.

	No article on colds is complete without a review of ineffective treatments:

	• Second-generation (nonsedating) antihistamines are generally ineffective for common cold symptoms.

	• Intranasal zinc is not recommended; it can cause permanent damage to sense of smell.

	• Echinacea does not appear to reduce a cold’s duration or severity.

	• Antibiotics are contraindicated—colds are viral, not bacterial.

	• Immune-boosting with vitamins and herbs does not seem to prevent colds.

	Colds are costly, with patients spending money on treatment, OTC products, and often, useless antibiotics. Colds are also responsible for millions of days of sick leave at work and school. Pharmacists’ best course of action is to help patients self-treat and make rational choices about OTC products when possible and to refer patients when complications are present.

Virginia Bartok is a pharmacist whose primary practice was in indigent care. She currently provides case management for several geriatric patients.

1. Fashner J, Ericson K, Werner S. Treatment of the common cold in children and adults. 

2. Singh M. Heated, humidified air for the common cold. 

3. Heikkinen T, Jarvinen A. The common cold. 

4. Arroll B. Non-antibiotic treatments for upper-respiratory tract infections (common cold). 

 2005;99:1477-1484. www.pharmacylibrary.com/otchandbook. Accessed October 2, 2014.

5. Tietze KJ. Respiratory disorders. In: Krinsky DL, Berardi RR, Ferreri SP, et al, eds. 

Handbook of Nonprescription Drugs: An Interactive Approach to Self-Care.

 17th ed. Washington, DC: American Pharmacists Association; 2011.

6. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Giffin SL. 2009 annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 27th annual report. 

7. FDA releases recommendations regarding use of over-the-counter cough and cold products [news release]. FDA website. www.fda.gov/NewsEvents /Newsroom/PressAnnouncements /2008/ucm116839.htm.  Accessed October 2, 2014.

8. Shehab N, Schaefer MK, Kegler SR, Budnitz DS. Adverse events from cough and cold medications after a market withdrawal of products labeled for infants. 

9. Mazer-Amirshahi M, Reid N, van den Anker J, Litovitz T. Effect of cough and cold medication restriction and label changes on pediatric ingestions reported to United States poison centers. 

10. Das RR, Singh M. Oral zinc for the common cold. 

11. Marshall I. Zinc for the common cold. 

12. Tran NP, Vickery J, Blaiss MS. Management of rhinitis: allergic and non-allergic. 

13. Berkowitz RB, Tinkelman DG. Evaluation of oral terfenadine for treatment of the common cold. 

14. Berkowitz RB, Connell JT, Dietz AJ, Greenstein SM, Tinkelman DG. The effectiveness of the nonsedating antihistamine loratadine plus pseudoephedrine in the symptomatic management of the common cold. 

15. Smith WM, Davidson TM, Murphy C. Toxin-induced chemosensory dysfunction: a case series and review. 

16. D’Cruze H, Arroll B, Kenealy T. Is intranasal zinc effective and safe for the common cold? a systematic review and meta-analysis. 

17. Karsch-Völk M, Barrett B, Kiefer D, Bauer R, Ardjomand-Woelkart K, Linde K. Echinacea for preventing and treating the common cold. 

18. Schroeder K, Fahey T. Over-the-counter medications for acute cough in children and adults in ambulatory settings. 

19. Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. 

Relief is available for common cold symptoms

The Common Cold: Treatment Algorithms

Patient profiles should be reviewed for drugs that may cause or exacerbate incontinence.

The squirming demeanor, the darting eyes, the awkward shuffle…as women age, they begin to understand “the look.” It’s the look that women get when something—or nothing obvious&mdash;causes the urge to void or an accidental urine leakage. Around 25% of young women, 44% to 57% of middle-aged or postmenopausal women, and 75% of older women in nursing homes experience urinary incontinence (UI).

 Dissecting “the look” reveals UI’s physical, psychological, and social repercussions. The squirming indicates the bothersome wetness and anxiety. The darting eyes indicate an acute need for the nearest restroom and fear that someone knows, and the shuffle is an attempt to prevent further incontinence.

The International Continence Society defines several types of UI (Table 1

 an increased risk of falls and fracture in the elderly,

 In the frail elderly, UI often prompts admission to nursing homes and increases medical expenditures.

Risk factors for UI include race (with Caucasians at highest risk), increasing age, family history of incontinence, neurologic conditions (eg, Parkinson’s, stroke, multiple sclerosis), impaired mobility, cognitive impairment, obesity, diabetes mellitus, constipation/fecal impaction, urinary tract infection, multiple vaginal births (especially >4 vaginal births), prior pelvic surgery or radiation, pelvic organ prolapse, and menopause.

Women want interventions that lead to continence (complete voluntary bladder control), allowing them the freedom to resume their normal activities. Continence is possible, but accurate diagnosis depends on the following

		Having the patient use a frequency volume chart/bladder diary and interpreting it correctly

		Excluding pathologic causes such as infection or prolapse

Patients who have mild to moderate UI may find that behavioral changes reduce incontinence. Pelvic floor strengthening exercises (eg, Kegel exercises) are effective for treatment of both urge and stress incontinence. It may take weeks to months for exercises to be effective, and they must be done correctly and regularly.

 Scheduled toileting during waking hours, especially for patients who have mobility issues, can help. Scheduled toileting includes prompting by caregivers, voiding at appointed times, or habit retraining so that accidents are preempted.

 In addition, weight loss has been shown to reduce symptoms of UI.

Constipation sometimes exacerbates UI, so treating it can reduce pressure. Note that antimuscarinic and anticholinergic drugs can cause or contribute to constipation.

 Some clinicians recommend caffeine elimination, but there is little evidence indicating it helps. Expert panels seem to believe that decreasing caffeine intake decreases fluid intake, and it’s the lessened fluid load rather than the lowered caffeine intake that helps with urgency symptoms.

 Many effective absorbent products are available to manage discomfort.

Medication can also cause UI; therefore, pharmacists should review patients’ profiles for drugs that may cause or exacerbate incontinence. Discontinuing medications that could cause cough, constipation, diuresis, or urinary retention is an often overlooked conservative approach (Table 2

Several medications can be employed to treat UI (Online Table 3

). Anti-cholinergic medications are the treatment of choice for many urinary tract symptoms; these agents block postganglionic muscarinic receptors on the detrusor muscle. Many patients discontinue drug therapy due to anticholinergic side effects (eg, dry eyes, dry mouth, blurred vision, increased heart rate, cognitive impairment). Approximately half of patients report significant improvement, but some authors maintain that achieving complete continence using drugs alone is unlikely.

 Few head-to-head studies have been conducted, so choosing a drug may require trial and error.

Table 3: Medications Used for Urinary Incontinence

						Systemic estrogen (oral or transdermal) is associated with increased UI or stress UI and is not recommended

				Urinary tract symptoms and urgency UI

						Oxybutynin is available as a topical gel and an OTC patch

						Dry mouth and constipation are frequent side effects; nausea, somnolence, dizziness, fatigue, and diarrhea are also concerns

				darifenacin, fesoterodine, solifenacin, tolterodine, trospium

						Drugs demonstrate similar effectiveness

						Discontinuation due to adverse effects is common

						Compliance rates are traditionally low

				Serotonin-noradrenaline uptake inhibitors: duloxetine, imipramine

						Response is inconsistent, and many women may discontinue the drug due to side effects

						Maintenance treatments are required due to waning effects after treatment is discontinued

Urinary Incontinence: Partnering with Patients for Success

Knowing these facts can help keep topical corticosteroid use safe and effective.

For patients with all kinds of skin problems, topical corticosteroids—prescription and OTC strength&mdash;are often soothing, as well as generally safe and effective.

 Let’s review 10 facts about these topicals.

1. Skin disorders prompt many physician visits.

 A 2013 Mayo Clinic study that included more than 140,000 patients revealed that skin disorders are the most common nonacute reason Americans seek health care.

 Topical corticosteroids, available since the 1950s, are the most prescribed dermatologic drugs and the mainstay of treatment for many conditions.

, even in generic form. Prices have risen over the past few years as generic manufacturers have consolidated (Table 1).

 Manufacturers invest $500,000 to $1.5 million to bring generic topical formulations to market, and if the FDA requires bioequivalence studies, the cost rises to $4 to $6 million. Generic topical steroids are still less costly than brand products.

 Due to the high cost, insurance companies monitor the estimated days’ supply closely to limit refills, and pharmacists must counsel patients to avoid waste. If patients need products for the long term and the prescription requires a large dose, using large sizes rather than dispensing multiple small tubes saves money.

 Topical steroids’ potencies reflect molecular modifications (Online Table 2

). For example, adding a 5-carbon valerate chain to the 17-hydroxyl position of betamethasone results in a compound more than 300 times more potent.9 Increasing potency also increases the risk of side effects (discussed below).

 The drug delivery vehicle—ointment, cream, lotion, or gel&mdash;can change the drug’s potency.

	Ointments’ occlusive effects make them ideal for dry, thick, or hyperkeratotic skin, but too greasy for hairy areas. Patients oftendislike their feel and become nonadherent.

	Creams’ vanishing nature increases cosmetic appeal but decreases steroid effectiveness. On acutely exudative lesions, creams can speed drying.

	Alcohol- or lubricant-based lotions feel better on hairy areas. Patients with acute exudative lesions prefer alcohol-based lotions, but individuals with chronic dry scalp lesions prefer lubricant-based lotions.

	Gels—liquids that behave like solids&mdash;have drying effects due to their water and alcohol content; they are good for wet, oozing rashes such as those caused by poison oak or ivy.

 Using topical corticosteroids on a patient’s face is tricky. Steroids can cause atrophy due to collagen loss, opportunistic infections, purpura, periorifical dermatitis, and rosacea exacerbation. Areas around the eyes and eyelids are especially thin and more vulnerable. In the elderly, progressive age-related skin changes elevate risk. Using the more potent topical corticosteroids increases the risk for adverse events, and so does using occlusion.

 Most products are FDA approved for application once or twice daily. Patients often think more is better, so pharmacists need to warn against this practice, especially with high-potency products. In chronic cases, physicians sometimes prescribe topical pulse therapy. This therapy generally requires the patient to apply high-potency product only on 2 consecutive days a week to minimize side effects; the remainder of the week, the patient uses a low-potency product.

 Side effects are rare when low- to high-potency topical steroids are used for 3 months or less, unless they are applied to intertrignous areas (areas where skin may rub together), on the face and neck, and under occlusive dressings.

 For ultra—high-potency topical steroids, if use exceeds 3 continuous weeks, tolerance and tachyphylaxis (decreased response) can develop, so prescribers should taper patients off these topicals. If patients need longer treatments, prescribers can use topical pulse therapy after a 1-week steroid-free period. This therapy reduces rebound effects.

 Patients rarely expect side effects (Table 31,4,13,15) from topicals, but side effects are possible and even likely if these products are used incorrectly. 

. Prescribers sometimes inadvertently allow excessive-potency topical steroid use, long duration of use, and topical steroid use on the face and neck. Community pharmacists are ideally placed to monitor response and provide advice about best practices.

 Applying topical drugs can be cumbersome. Patients may misunderstand instructions from prescribers.

 Topical corticosteroids present a conundrum: too little hampers response, and too much increases the risk of adverse effects.

	Pharmacists must reinforce other clinicians’ instructions and include additional reminders, including these points