Melissa Laracy, 2017 PharmD Candidate

Everyone's had one and will have another: a common cold. It's the most common acute illness in the United States.

Americans suffer from 1 billion colds every year. Children contract 6 to 8 colds annually, while adults average 2 to 4.2 It’s a benign, self-limiting condition, but it’s irritating enough to stimulate a robust demand for OTC products to treat symptoms. Americans spend an average $300 million and $4.2 billion on products to prevent and treat cold symptoms yearly, respectively.

Health care professionals (HCPs) usually recommend OTC products as first-line treatments.

They must evaluate these agents’ safety for each patient before making suggestions.

Many cough and cold remedies are multi-ingredient products.

Such products reduce pill burden, but also increase the risk of drug duplication and toxicity. Consumers may accidentally exceed maximum recommended dosages, especially for acetaminophen (adult maximum dosage is 4 g/day). Retail clinicians are responsible for educating patients to check ingredient lists.

HCPs must also be aware of potential drug—drug interactions to ensure that patients use these products safely.

Even though most cough and cold products are available without a prescription, they can have significant adverse effects (AEs) and drug interactions.

Practitioners need to warn patients of potential harms.

Given either topically or systemically, nasal decongestants clear a stuffy nose.

Table 18,9 lists their significant drug—drug interactions. Decongestants have additive effects if taken with other sympathomimetics, so use should be restricted or monitored.

Cold symptoms are not histamine mediated. Regardless, antihistamines—and only the first-generation antihistamines&mdash;are used for their anticholinergic side effects (not to block histamine release). They reduce cold-related sneezing and rhinorrhea.

Consult Table 28,9 for a list of drug interactions.

Acetaminophen and ibuprofen relieve headaches and body aches associated with colds, but they have a significant number of drug interactions (see Table 38,9 ).

Retail clinicians should also caution patients to avoid alcohol consumption because of the risk of liver toxicity with acetaminophen and gastrointestinal bleeds with ibuprofen.

Antitussives (see Table 48,9) are used to suppress coughs.

Recommend these products for nonproductive coughs (ie, mucus is not produced). Expectorants loosen mucus, allowing patients to cough it out.

Complementary and Alternative Medicine (CAM)

Patients use some common CAM products for cough/cold including zinc, vitamin C, and echinacea.

These have some drug interactions (see Online Table 5). Retail clinicians should inform patients that rather than treating the common cold, these products can reduce its duration. Oral zinc is only effective if taken within 24 hours of symptom onset, and prophylactic vitamin C can reduce the duration and symptoms of colds by 8%.

Health care professionals should always educate patients on nonpharmacologic methods. Rest, hydration, and humidified air are key for recovery.

Saline nasal spray for congestion and honey for cough may also help.

The multitude of products available for cough and cold treatment can be confusing for many consumers. Box after box, they line OTC shelves. Physician and pharmacist expertise can guide selections. Before making any recommendations, it’s important to ask what other agents—OTC, prescription, and herbal&mdash;patients are taking so that interactions may be avoided.

Melissa Laracy is a 2017 PharmD candidate at the University of Connecticut School of Pharmacy.

1. Sexton DJ, McClain MT. The common cold in adults: treatment and prevention. UpToDate website. uptodate.com/contents/the-common-cold-in-adults-treatment-and-prevention. Accessed July 22, 2016.

2. Simasek M, Blandino DA. Treatment of the common cold.

3. LSS Financial Counseling. The cold and flu season is here, and guess how much it will cost? October 31, 2013. LSS Financial Counseling website. blog.conqueryourdebt.org/2013/10/31/cold-flu-season-guess-much-will-cost/. Accessed July 22, 2016.

4. Smith SM, Schroeder K, Fahey T. Over-the-counter (OTC) medications for acute cough in children and adults in community settings.

5. Montauk SL, Rheinstein PH. Appropriate use of common OTC analgesics and cough and cold medications.

Monograph No. 1. 2002. www.fda.gov/ohrms/dockets/dailys/02/Aug02/082202/80022395.pdf. Accessed August 1, 2016.

6. FDA. Notice to industry: final guidance for over-the-counter products that contain acetaminophen. November 16, 2015. FDA website. www.fda.gov/Drugs/DrugSafety/ucm310469.htm. Accessed July 29, 2016.

7. FDA. Drug interactions: what you should know. September 25, 2013. FDA website. www.fda.gov/drugs/resourcesforyou/ucm163354.htm. Accessed July 22, 2016.

8. Lexicomp, Inc. (Lexi-Drugs, Interact). Lexi-Comp Mobile. Accessed July 29, 2016.

9. Micromedex Solutions. http://www.micromedexsolutions.com/home. Accessed July 29, 2016.

10. CDC. Clinical immunization safety assessment (CISA) project current studies. August 28, 2015. CDC website. cdc.gov/vaccinesafety/ensuringsafety/monitoring/cisa/studies.html. Accessed July 29, 2016.

11. Livingston C, Cozzens J, Hamilton A. FPIN’s clinical inquiries. Treatments for symptoms of the common cold.

2013;88(12). aafp.org/afp/2013/1215/od3.html. Accessed September 9, 2016.

12. Goldman RD; Canadian Paediatric Society, Drug Therapy and Hazardous Substances Committee. Treating cough and cold: guidance for caregivers of children and youth.

Articles

The Common Cold: Acute Illness, Drug Interaction Potential

Today, 99,478 of the 120,001(83%) of patients on the organ transplant waiting list in the United States still await a kidney transplant.

In 2015, US surgeons transplanted only 17,800 kidneys.

More patients remain on the waiting list than those receiving a transplant, and approximately 15% of those on the waiting list will die waiting.

Finding ways to improve the number of organ donors would increase the size of the deceased donor pool. Targeting the living donor pool by increasing the length and number of kidney transplant chains is another option.

To start these chains, altruistic individuals donate kidneys to complete strangers. This sets off a domino reaction, in which recipients’ loved ones donate to others in gratitude.

In recent years, these chains have gained momentum, changing many patients’ lives.

Kidneys can come from living or deceased donors. Kidney registries use living donors in 3ways (

) and prefer them because of long-term results and lower risks of complications and rejection.

Kidneys from live donors last twice as long as those from deceased donors.

In addition, identifying a living donor significantly shortens wait times. Although recipients may wait on the deceased donor waiting list (DDWL) for more than 5 years, the average wait time for a living donor match from the National Kidney Registry (NKR) is 5 months.

·      Occurs when the donor knows the recipient, is a compatible match, and donates to that individual

·      Occurs if a potential donor is not a match for his or her intended recipient; an alternative known as paired exchange donation is possible.

·      Donor #1 donates his or her kidney to another recipient who will provide a compatible donor for recipient #1

·      Two incompatible pairs are matched to allow 2 otherwise-impossible transplants to occur

·      Occurs when a donor gives a kidney to a stranger, initiating a chain

·      Synonymous terms include nondirected and Good Samaritan donation

It’s a fairly straightforward procedure. For donors, the operation can be performed laparoscopically with small incisions, a camera, and instruments that remove the kidney.

It only takes 2 to 3 hours and patients are usually discharged after 2 nights in the hospital.

The donor’s remaining kidney performs the work that both kidneys had prior, with no long-term health consequences.

For the recipient, the operation is usually 2 to 4 hours.

Once the kidney is placed into the abdomen, the surgeon sews the donor kidney’s renal artery and vein to the recipient’s external iliac artery and vein, allowing blood to flow properly. Then, the surgeon connects the donor ureter to the recipient’s bladder, allowing urine to pass through the kidney.

Hospital recovery time is usually around 3 to 7 days, during which time the health care team monitors for kidney function and graft rejection. Patients also begin a regimen of antirejection medications for life.

Among organ transplants, kidney transplants have some of the highest success rates. Ninety-seven percent of transplanted kidneys function normally after one month, and 83% function normally 3 years post-transplant.

Several blood tests ensure donor-recipient compatibility. The first is blood type (A, B, O, or AB positive or negative),

which must be either identical or compatible. Blood type O-negative is the universal donor, so any patient can receive a kidney from an O-negative donor. AB-positive is the universal recipient, so patients with AB-positive blood can receive a kidney from anyone.

After blood type is matched, the pathology lab performs tissue typing by identifying human leukocyte antigens (genetic markers on cells) in blood samples.

Transplants with the best and longest success rates have perfect matches for all 6 antigens, but some degree of mismatch is allowed.

The pathology lab also conducts percent reactive antibody tests to assure compatibility, evaluating the recipient for antibodies that may have formed from a previous exposure to antigens. The more antibodies present, the more difficult it is to find a match.

A serum crossmatch determines if the donor and recipient are compatible. Donor cells are incubated in the recipient’s serum and if the recipient has antibodies against the donor’s cells, those cells will be destroyed and it will be termed a positive crossmatch. If this happens, the individuals are incompatible and a transplant is impossible. If, however, a patient’s samples pass all of these tests, then the pair is a match and the transplant can occur.

The transplant team considers many factors during the match process. One-third of willing donors are incompatible with their intended recipients.

Traditional paired kidney donation has the potential to leave many of these pairs unmatched.  Kidney chains can be a solution to this problem.

Paired exchange and altruistic donation not only increase the size of the kidney donor pool, but also stimulate additional compatible matches.

The first successful living donor kidney transplant occurred in 1954 between identical twins in Boston. The first living unrelated and nondirected donor transplants occurred about a decade later, but it took many years for the living donor pool to grow.

Before chains were possible, transplantation programs and specialists made numerous improvements to organ donation policy and procedure. Kidney chains evolved in a step-wise manner from other types of living donation. Direct donation first began in the 1950s. Although the idea of paired exchange was first published in 1986, it wasn’t until 2000 that the first recorded exchange occurred in the United States.

Paired exchange programs emerged to facilitate matches, first within a single transplant program, and then between different programs across the country. Dr. Robert Montgomery, renowned transplant surgeon and director of NYU Langone Medical Center’s Transplant Institute, suggested domino paired kidney donation in 2006.

In domino exchange, altruistic donors are matched to recipients with incompatible donors, and the incompatible donors promise to donate to a patient on the DDWL.

The formation of the first never-ending altruistic donor chain was the next milestone in living kidney donation.

Rather than donating to patients on the DDWL, kidneys are donated to patients who are incompatible with willing donors. Those willing donors become “bridge donors” who continue the chain as recipients of incompatible pairs match with bridge donors.

Theoretically, such chains could go on forever. The first chain was launched by Michael Rees, a transplant doctor at the University of Toledo Medical Center and founder of the Alliance for Paired Kidney Donation in 2000. The chain occurred in 2007 and yielded 10 kidney transplants.

Garet Hil, president of Hil & Company LLC and founder of the NKR in 2007, has also been instrumental in organizing matches and chains throughout the country.

The most obvious is the expansion of the donor pool and higher-quality matches for the greatest number of patients. When the exchange is between 2 pairs, one recipient may receive a much higher-quality match than the other. Even though both exchanges are compatible, better HLA matches could exist and be found using chain donation techniques.

Even more beneficial is when compatible pairs with blood type O donors and A, B, or AB recipients enter a chain.

Traditionally, type O patients on the waiting list have longer wait times because type O kidneys can be allocated to all blood types.

When such compatible pairs participate in a chain, the intended recipient can find a stronger match, and the type O donor can match to a type O recipient in need.

Another advantage over paired exchange is that chains eliminate the need for simultaneous transplant surgeries. Paired exchange transplants need to be performed simultaneously to prevent donor withdrawal.

If the surgeries aren’t completed at the same time, one donor could back out of the exchange, leaving a recipient without a kidney and without their original intended donor. Chains don’t exhibit this problem because they start with altruistic donors who expect nothing in return. Surgeries within chains can be scheduled more flexibly and at the patients’ convenience.

An additional concern with paired exchange is the repercussions of swap failures.

If a procedural complication occurs, surgeons are unable to complete the transplant. This is termed a swap failure. In paired exchange, a recipient has lost a compatible kidney and may also have lost their incompatible donor as the procedures are done simultaneously. In a chain, swap failures end the chain, but recipients aren’t further harmed by the loss of their incompatible donor. They still have the opportunity to participate in a different chain because their intended donor has not donated a kidney yet.

Finally, chains are particularly advantageous for highly sensitized and blood type O recipients.

Sensitized individuals have high levels of HLA antibodies as a result of a previous exposure through blood transfusions, pregnancy, or prior transplants.

Sensitized patients wait on the DDWL significantly longer than other patients due to the difficulty in finding a compatible donor. Kidney chains produce more transplants for these 2 groups by increasing the donor pool.

One concern is the risk of breaking a chain.

Theoretically, these chains could endure forever, but realistically, they don’t. Eventually, chains end when a compatible pair is not available or a donor is difficult to match. They also end if donors have extended wait times.

Although donors may change their minds at any moment and back out of chains, it is unlikely.

Most donors are so grateful that their loved one received a kidney, they can’t way to “pay the gift forward.”

The NKR reported only one broken chain out of 83 in 2015, and zero broken chains out of 20 as of March 31, 2016.

Some chains also end intentionally when a recipient qualifies for a kidney from the DDWL.

The living chain ends, but the final recipient benefits by receiving a needed kidney that he or she may not have received otherwise.

The real debate is over the ethics of kidney chains. When altruistic donors come forward, their kidneys could start chains or be given to individuals on the DDWL. The popularity of chains diverts potential living donor kidneys, which have significantly longer graft survival times, away from patients who lack living donors.

However, some argue that chains are beneficial for the DDWL by preventing kidney transplant chain recipients from competing with other patients on the list.

Those who remain on the DDWL will be more likely to receive a transplant. Blood type O patients on the DDWL are at even more of a disadvantage. Recipients with this blood type already have the longest wait times, with kidney chains further increasing these wait times.

Altruistic donors’ motives also need to be considered. Large kidney transplant chains tend to attract media coverage. Some individuals only consider becoming altruistic donors for media attention. Maintaining the anonymity of transplant chain participants could combat this issue. It’s equally important to ensure that potential donors aren’t coerced, exploited, or given financial compensation as these raise further ethical concerns. Careful screening, education, and informed consent of potential altruistic donors help maintain ethical standards in chain transplants.

Another concern is the kidney allocation process.

Lacking government regulation, kidney registries are able to weigh certain factors more heavily than others. When determining individual patients’ transplant needs, kidney registries may consider HLA and ABO status, wait time, match difficulty, age, other health conditions, time until or duration on dialysis, history of kidney transplant, previous organ donation, and formation of the longest chain possible.

Several nonprofit agencies facilitate the formation of chains. Registries use complex software algorithms to find the best match for each patient. Some organ transplant centers conduct exchanges exclusively at their center. The use of national registries, however, expands the donor pool and provides patients with a greater likelihood of successful transplant and increased graft survival times. The NKR has the largest donor pool in the world, prompting better matches and more opportunities to repair failed swaps.

Registry software is designed to optimize ABO and HLA compatibility. Other patient-specific characteristics are factored in, such as age and travel preference.

One potential problem that arises from national registries is location. If donor-recipient matches span the country, the donor or the organ will need to travel. Many donors prefer to stay at home where they can recover near friends and family; in these cases, organ shipment is usually preferred. Organs can be shipped on commercial airlines at minimal cost. Local organ procurement organizations deal with these transactions’ details.

Such organizations also manage the transportation of deceased donor organs successfully. Some experts have reservations about the function of kidneys that have prolonged cold ischemic times. This may be why some transplant specialists prefer conducting local exchanges at the same center, even if the match isn’t as strong.

However, studies have shown that prolonged cold ischemia time does not affect graft function.

Leaders in the field of kidney transplants attended a conference in Herndon, Virginia, in 2012 to discuss the formation of a national registry. Opinions were split between establishing one registry or having multiple registries (the current arrangement) to manage the matching and allocation processes. Mathematically, one large pool of donors creates more potential matches than 2 smaller pools do. In addition, including pairs in multiple registries could create problems with chain construction if two registries want to use the same donor. However, competing registries prefer remaining separate. Competition fuels innovation, which unification of the registries may destroy. The general consensus was to work toward the formation of single national registry in the future.

The benefits of kidney transplant chains are already being realized. They multiply the impact that altruistic donors create.

Currently, the longest living kidney donor chain is the University of Alabama at Birmingham Kidney Chain. Started in December 2013, it has since grown to include 112 individuals, yielding a total of 56 kidney transplants as of December 2015.

The longest multihospital chain to date involved 68 individuals, 34 kidneys, and 26 hospitals across the United States.

It happened over the course of 3 months, ending on March 26, 2015.

Kathy Hart was the Good Samaritan who started this chain, ending with Mitzi Neyens. After living with kidney disease for 30 years, Neyens’ condition began to rapidly decline at the age of 77, but her age precluded her from being added to the DDWL. Living organ donation was her only option, and without this chain, she probably wouldn’t have found a donor. This particular chain included 16 highly-sensitized individuals who could have waited years on the DDWL before a compatible match was identified.

Many multicenter transplant chains wouldn’t be possible without the efforts of national registries. The NKR alone has initiated 329 chains, facilitating 1513 kidney transplants. It has also arranged 83 loops (a series of swaps without an altruistic donor), facilitating 194 transplants. The NKR is responsible for organizing a total of 1827 kidney transplants as of July 2016.

lists the longest and most successful chains/swaps from the NKR. The longest chain to date is Chain #357, which enabled 35 transplants.

: Longest National Kidney Registry Chains

(multiply by 2 for total number of participants)

Melissa Laracy, 2017 PharmD Candidate

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The Common Cold: Acute Illness, Drug Interaction Potential

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