Solid-Organ Transplantation about Donor Risk Factors

For the first time in 15 years, there has been documented transmission of the human immunodeficiency virus (HIV) through solid-organ transplantation.¹ Although transmission of infectious agents through transplantation is rare,² such cases raise important questions about how informed consent for transplantation should be obtained and about the type of resource that transplantable organs represent.

Among the questions raised are the following: Should potential recipients be informed about the general risks associated with transplantation or those specifically associated with an identified organ? Should the risks engendered by the behavior of donors be treated differently from those associated with the medical profiles of donors? Finally, is the supply of transplantable organs a singular public good to be distributed to maximize public health or is it a market of intermittently available goods from which eligible recipients might select in order to maximize their own well-being?

The Chicago Case

A 38-year-old man died after a motor vehicle accident in January 2007. His liver, heart, and both kidneys were subsequently transplanted into four recipients. At the time of the donor's death, all routine tests for transmittable diseases² were negative. However, the local organ-procurement organization and the transplantation surgeons to whom the organs were sent knew that this donor had a behavioral risk factor that increased the possibility that the antibody-based assays for HIV and other viruses might show false negative results.^1,3

All four organ recipients have since tested positive for both HIV and the hepatitis C virus (HCV). At least one of the recipients is considering a suit against the transplantation center and the local organ-procurement organization, charging that she was harmed by not being notified of the donor's above-average risk of HIV and, therefore, was denied the opportunity to decline the donation. Her attorney has declared, "it's up to the patient . . . to make the decision whether to incur the risk."³

Behavioral Risks among Donors

A well-known limitation of the safety of organ transplantation is that antibody-based tests to detect viruses have poor sensitivity within the first few weeks after infection.² Although more sensitive nucleic acid–amplification tests are now used in some regions, even these tests do not fully eliminate the possibility of a false negative result. Data from studies involving tissue donors show that between 1 of 55,000⁴ and 1 of 161,000⁵ donors are infected with HIV, despite negative antibody-based tests, and that the addition of nucleic acid testing reduces the rate of false negative results by two thirds.^4,5

Certain donors have above-average risks of false negative HIV tests because their behaviors may generate more new infections. Nonetheless, persons with risk factors for HIV that have been identified by the Centers for Disease Control and Prevention (CDC)⁶ are commonly donors for solid-organ transplantation. Table 1 indicates that during the period from 1995 to 2006, 6% of donors in our donor service area had risk factors that were consistent with the CDC criteria.

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Acute calculous cholecystitis

Acute calculous cholecystitis is a complication of cholelithiasis, a condition that afflicts more than 20 million Americans annually¹ and results in direct costs of more than $6.3 billion.² Most patients with gallstones are asymptomatic. Of such patients, biliary colic develops in 1 to 4% annually,^3,4,5 and acute cholecystitis eventually develops in about 20% of these symptomatic patients if they are left untreated.⁶ Such patients tend to be somewhat older than those with uncomplicated symptomatic cholelithiasis. Most patients with acute cholecystitis have had attacks of biliary colic, but some have had no previous biliary symptoms.^3,4,5 After an initial attack of acute cholecystitis, additional attacks of pain or inflammation are common.⁷ In a small proportion of patients, acute cholecystitis may coexist with choledocholithiasis, cholangitis, or gallstone pancreatitis.

About 120,000 cholecystectomies are performed for acute cholecystitis annually in the United States. However, the incidence of acute cholecystitis seems to be falling because of the greater acceptance by patients of laparoscopic cholecystectomy as a treatment for symptomatic gallstones.⁸ About 60% of patients with acute cholecystitis are women. However, acute cholecystitis develops in men more frequently than would be expected from the relative prevalence of gallstones (about half that in women),¹ and cholecystitis tends to be more severe in men.⁹ In patients with diabetes who have symptomatic gallstones, acute cholecystitis seems to develop more frequently than in patients without diabetes, and such patients are more likely to have complications of acute cholecystitis when it occurs.¹⁰

Pathogenetic Features

More than 90% of cases of acute cholecystitis are associated with cholelithiasis (acute calculous cholecystitis). The key elements in pathogenesis seem to be an obstruction of the cystic duct in the presence of bile supersaturated with cholesterol.¹¹ Brief impaction may cause pain only, but if impaction is prolonged over many hours, inflammation can result. With inflammation, the gallbladder becomes enlarged, tense, and reddened, and wall thickening and an exudate of pericholecystic fluid may develop. The inflammation is initially sterile in most cases, but secondary infection with microorganisms in the Enterobacteriaceae family or with enterococci or anerobes occurs in the majority of patients.^12,13 The wall of the gallbladder may undergo necrosis and gangrene (gangrenous cholecystitis). Bacterial superinfection with gas-forming organisms may lead to gas in the wall or lumen of the gallbladder (emphysematous cholecystitis). Without appropriate treatment, the gallbladder may perforate, with the development of an abscess in the right upper quadrant or liver or generalized peritonitis.

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Tobacco

Tobacco usage has been demonstrated to be either the primary or contributing factor for numerous cancers, including lung, oral, bladder, pancreas, esophagus, stomach, and many others.66 Declines in incidence and mortality for tobacco-related cancers92 have been observed following declines in smoking prevalence, primarily due to smoking cessation, between 5 and 20 years previously. Recently, the trends in current smoking prevalence have been stable (Table 3)

, though smokers are smoking fewer cigarettes per day. Recent leveling of tobacco-use prevalence raises concern that the downward trends in tobacco-related cancers may eventually flatten as well. Clearly, tobacco remains the most modifiable factor for cancer prevention, thus US public policy to further discourage tobacco use is the most important continuing opportunity to decrease future cancer incidence.

Obesity. Since the early 1980s, an epidemic of overweight and obesity has been occurring in the US population. While recent data suggest that this upward trend may be moderating among women, increases continue in men.12 Obesity increases the risk of cancer at multiple sites, including the endometrium, kidney, colon, postmenopausal breast, and adenocarcinoma of the espophagus.48 The effect of obesity is clear on trends in cancers such as adenocarcinoma of the esophagus90,91 and kidney.71 Despite increasing prevalence estimates of obesity, incidence of colorectal cancer has continued to decline, as has postmenopausal breast cancer. These declines would likely have begun sooner and would have been steeper if it were not for the obesity epidemic. If the obesity epidemic can be stabilized and reversed in the coming years, substantial reductions in incidence of obesity-related sites can be expected. Efforts should be directed to discourage weight gain and encourage weight loss among the US population to reduce risk of cancer, as well as other chronic diseases.

Screening. Screening for early cancer detection in the general population is currently recommended for breast, colorectal, and cervical cancers. Additionally, providing information to support informed choices about screening for prostate cancer is recommended.93 The relationship between screening and cancer incidence is complex. In some instances, screening can reduce incidence through the detection and successful treatment of precursor lesions, such as for cervical intraepithelial neoplasia and colorectal adenomas, thereby lowering cancer incidence. For prostate cancer, however, screening leads to increased cancer incidence through the identification of small cancers that might not become clinically apparent until years into the future, if ever. Thus, screening can reduce cancer mortality while, at the same time, increasing cancer incidence. The balance of risks and benefits from the identification of cancers by screening can only be properly assessed in randomized, controlled screening trials. Continued public health effort should be focused on continuing to obtain better information about the benefits and risks of screening, especially for prostate and lung cancers, and on achieving high screening rates in the general population for those cancers showing evidence-based screening benefits.

Race/Ethnicity. Racial and ethnic differences exist in the rates of cancer incidence in the United States. Compared with non-Hispanic Whites, African Americans experience higher incidence rates for cancers of the colorectum, lung, prostate, liver, kidney, and cervix, and Hispanics, Asians, and Pacific Islanders experience higher incidence of cancers of the liver, stomach, and cervix.63 Racial differences in cancer incidence and mortality rates are complex and poorly understood. Disparities in cancer incidence, survival, and mortality by race and ethnicity seem to be due to a combination of factors, including biological, behavioral, cultural, and economic, as well as structural factors in health care. Changes in the racial and ethnic demographics of the United States are likely to contribute to transforming future patterns of cancer incidence. In 2001, 7% of non-Hispanic White adults aged 18 to 64 years lived below the poverty level, compared with 19% of African Americans and 16% of other minorities.94 Members of some racial and ethnic minority groups also tend to have less education and are less likely to have health insurance.95–97 As lack of insurance leads to lower utilization of screening programs and to less adequate treatment for cancer, it follows that public policy strategies encouraging health care system reforms to reduce barriers to clinical preventive services such as cancer screenings, tobacco cessation support, and nutritional counseling could have an important effect on disparities in future cancer incidence.93,96

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American Cancer Society Challenge Goal to Decrease Cancer Incidence by 25% Between 1992 and 2015

In 1998, the American Cancer Society (ACS) set a challenge goal for the nation to reduce cancer incidence by 25% over the period between 1992 and 2015. This report examines the trends in cancer incidence between 1992 and 2004. Trends were calculated using data on incident malignant cancer cases from the Surveillance, Epidemiology, and End Results (SEER) Registry. Delay-adjusted incidence trends for all cancer sites; all cancer sites without prostate cancer included; all cancer sites stratified by gender, age, and race; and for 20 selected cancer sites are presented. Over the first half of the ACS challenge period, overall cancer incidence rates have declined by about 0.6% per year. The greatest overall declines were observed among men and among those aged 65 years and older. The pace of incidence reduction over the first half of the ACS challenge period was only half that necessary to put us on target to achieve the 25% cancer incidence reduction goal in 2015. New understandings of preventable factors are needed, and new efforts are also needed to better act on our current knowledge about how we can prevent cancer, especially by continuing to reduce tobacco use and beginning to reverse the epidemic of obesity.

Cancer incidence during the time period from 1992 to 2004 has been decreasing, due mostly to a favorable trend among men and among those aged older than 65 years. However, there is considerable variation across cancer sites in both the magnitude and the direction of cancer incidence trends over this time period. Here we discuss the likely reasons for variations in incidence trends and speculate on the changes that can be expected between now and the year 2015. We first discuss trends by specific cancer sites and then by cross-cutting issues of tobacco, obesity, screening, and race/ethnicity.

Cancer Sites
Prostate Cancer. The prostate is the leading site for cancer incidence among US men.1 Prostate cancer incidence has been extremely variable in the past 20 years, largely due to the advent of PSA screening. A sharp increase in incidence began in the late 1980s, almost certainly due to the advent of PSA testing and the detection of a high number of previously undiagnosed, prevalent cases.20 Despite approximately 40% higher rates of prostate cancer incidence among African Americans as compared with Whites, declining trends are similar for both Whites and African Americans. Modifiable nutritional factors may also be important in prostate cancer, especially vitamin E and selenium.21 If the ongoing Selenium and Vitamin E Cancer Prevention Trial (SELECT) finds that either type of supplement can reduce prostate cancer risk, there could be benefits for lower incidence in the coming decade.22 Prostate cancer incidence can be reduced with finasteride chemoprevention, which inhibits the conversion of testosterone to dihydrotestosterone, but this medication has not been commonly used for this purpose because of concern about possible adverse effects leading to cancers with higher Gleason grades.23 Hopefully, findings from PSA screening trials will clarify the value of screening for reducing morbidity and mortality from prostate cancer, as well as the overall impact on duration and quality of life.24,25 The trends of declining prostate cancer incidence will be largely dependent on the rates of PSA testing in the years to come.

Breast Cancer. The breast is the leading site of cancer incidence in US women.1 Over the time period of 1992 to 1999, no substantial changes in overall incidence rates of invasive breast cancer were observed, but after 1999, breast cancer incidence began to decline. Initially the decline was likely due to the saturation of mammography screening, which had already identified many prevalent early breast cancers, ultimately impacting treatment and future mortality trends.18–19 This decline steepened substantially after 2002, primarily due to declines in estrogen receptor-positive tumors among women aged 50 to 69 years.26 This steeper decline since 2002 may be due to the combined effects of a decline in the rate of mammography screening and the sudden decline in HT following the 2002 publication of the Women's Health Initiative for combined estrogen and progestin.13,26,27 Both of these factors will cause a continued decline in breast cancer incidence in the coming years. The obesity epidemic has had adverse effects on breast cancer incidence trends. Without past increases in obesity, incidence declines might have been steeper and seen much earlier. According to the National Health and Nutrition Examination Survey, there has been no significant increase in prevalence of obesity among women between 1999 to 2000 (33.4%) and 2003 to 2004 (33.2%).12 Despite this suggestion that obesity might be stabilizing among women, the current prevalence of overweight and obesity is still quite high (62%).12 Weight gain and excess adiposity are important modifiable risk factors for postmenopausal breast cancer.28 Therefore, if the obesity epidemic can be slowed and reversed in the coming decade, this could cause additional reductions in future breast cancer incidence. Future declines in breast cancer incidence may also be seen as the consequence of removal of atypical hyperplasia and ductal carcinomas in situ that were identified as suspicious lesions by mammography in past years. Tamoxifen and raloxifene have both been shown to substantially reduce the risk of incident breast cancer.29,30 The safety profile for tamoxifen discourages its widespread use, but raloxifene seems to have a better balance of risks and benefits.30 Raloxifene, currently used in the prevention and treatment of osteoporosis, was prescribed in only 12% of patient visits for osteoporosis in 2003.31 If the use of raloxifene increases substantially in the coming years, breast cancer incidence may be expected to fall. In the coming decade, the longer-term effects of decreased use of HT, increased chemoprevention, and slowing of the obesity trends should lead to continued decreases in breast cancer incidence rates.

Lung Cancer. The lung is the second leading site for cancer incidence and the leading site for cancer death among both US men and women.1 Lung cancer incidence rates are approximately 1.7 times higher in men than in women. The downward trend of lung cancer incidence in men is exceeding the 25% reduction goal, but the trends among women are not (see Figure 1). The primary cause of lung cancer is tobacco use, so incidence trends are largely a reflection of tobacco-use trends over the preceding 20-year period.32,33 The prevalence of smoking declined from 52% to 33% among men and from 34% to 28% among women during the time period from 1965 to 1985. Between 1985 and 1995, there was about a 5% decrease in the prevalence of tobacco use among both men and women.34 Despite a persistently higher rate of lung cancer among African Americans than among Whites, a steeper decline has been observed for African Americans compared with Whites over this time period, likely due to historical changes in smoking. Declines in lung cancer incidence have also been observed due to reductions in occupational carcinogen exposures; however, the relative contribution to overall lung cancer rates of these exposures is small compared with tobacco use.32 Screening is not recommended for lung cancer in the general population, but low-dose computed tomography (CT), chest x-ray, sputum cytology, molecular sputum testing, or a combination of these tests are still under investigation and, therefore, may hold promise.24,35–40 Promising findings for screening with spiral CT scans have led to the implementation of large randomized clinical trials (RCTs) now underway that will be completed by 2010.37 Apart from possible effects of screening, the incidence rates for lung cancer will likely decline in the coming decade as a consequence of past tobacco trends. If CT screening begins to be used widely, then incidence rates will substantially increase as an artifact of the initiation of screening and the detection of prevalent cases, as was observed for prostate cancer in the early 1990s. Apart from this potential artifact of screening, the major factor that will determine lung cancer incidence in the coming decade is the past history of tobacco use. Incidence will, therefore, likely continue to decline among men and soon begin to decline among women.

Colorectal Cancer. Modifiable risk factors associated with the development of colorectal cancer include physical inactivity; adiposity; cigarette smoking; and diets high in red meats, processed meat, or high energy intake, while preventive factors include the use of nonsteroidal anti-inflammatory drugs (NSAIDs); HT; and diets high in fruits, vegetables, calcium, and/or vitamin D.41 Colorectal cancer incidence rates increased until 1985, when they began to decline.42 The reasons for this decline are not clear, but could be tied to downward trends in cigarette smoking, increasing NSAID use, and increasing HT use. The recent decline in HT use may adversely affect colorectal cancer trends among women in the coming years, as HT reduces risk.13 Recent trials have demonstrated the potential for NSAIDs to reduce colorectal adenomas, but adverse effects from these agents will limit their widespread use for that purpose.43,44 Colorectal screening (especially colonoscopy and flexible sigmoidoscopy) leads to the identification and removal of adenomas, thus substantially reducing the risk of incident colorectal cancer.45 Colorectal screening rates (mostly colonoscopy) have been increasing in recent years (Table 3). Colorectal screening is higher among Whites than among African Americans,46 which may help explain the steeper decline observed among Whites. The current rate of decline in the incidence of colorectal cancer is on target to meet the 25% reduction challenge goal for 2015. This favorable trend in colorectal cancer incidence is occurring in spite of the obesity epidemic. If obesity trends can be improved and if we can continue progress in the use of colonoscopy for colorectal screening, the reduction in incidence of colorectal cancer may well exceed the 25% goal.

Uterine Cancer. The primary risk factor likely to affect the current trends in endometrial cancer is obesity.47,48 Obesity likely influences endometrial cancer risk in premenopausal women by causing androgen excess with altered ovarian physiology, whereas in postmenopausal women, adipose tissue increases estrogen production through the conversion of androgens to estrogens by aromatase.49 Another important risk factor for uterine cancer is the use of unopposed estrogens in HT.50 It is likely that the sharp declines in the use of systemic unopposed estrogen8 after 20028 have led to only a small decrease in incidence, as probably only a small number of women who have not had hysterectomies would have been taking unopposed estrogen. However, a recent report from the Women's Health Initiative suggests a lower prevalence of coronary artery calcification among postmenopausal women aged 50 to 59 years who had undergone hysterectomy and received conjugated equine estrogen as compared with those who received placebo.51 These findings, along with earlier findings suggesting that combined HT confers greater postmenopausal breast cancer risk13 than estrogen alone,14 may lead to an increase in the use of unopposed estrogen therapy in women with uteri, thus increasing their risk of endometrial cancer. Surveillance of specific prescribing factors for HT should be monitored. Overall, the high obesity prevalence may influence future trends. Therefore, the most reasonable prediction would be a continued stable rate of uterine cancer.

Bladder Cancer. Bladder cancer is the fourth leading cancer among US men.1 The primary modifiable risk factors for bladder cancer are cigarette smoking and occupational exposures to carcinogens.52 However, the anticipated decline in incidence of bladder cancer due to past reductions in tobacco use and occupational exposures has not been seen over the time period of 1992 to 2004. The reasons why bladder cancer rates have remained unchanged are not clear, hence it is not possible to confidently predict changes in the coming decade.

Non-Hodgkin Lymphoma. Very little is known about modifiable risk factors for non-Hodgkin lymphoma other than HIV/AIDS, Epstein-Barr virus, herpes virus 8, human T-cell lymphotropic virus, and immunosuppressive drugs.53 Potential roles of other infectious agents and occupational and environmental factors such as benzene54 or polychlorinated biphenyls,55 as well as others,56 are unclear. The most reasonable prediction for the coming decade is, therefore, continuation of the past trend of an increase in rates.

Melanoma. Melanoma rates have been increasing substantially in recent years. This is likely due to the combined effects of previous sun exposures and increased diagnosis of very small cancers due to improved awareness and surveillance of pigmented lesions.57 There has been a modest 8% increase in sunscreen use among adolescents from 1998 to 2004,58 but no significant decrease in reported sunburn in the previous summer (69% versus 72%).46 As most melanoma occurs in older people, it is likely rates will continue to increase into the coming decade resulting from past sun exposures.

Ovarian Cancer. The few modifiable risk factors that decrease risk include oral contraceptives, hysterectomy, tubal ligation, and high parity.59 In 1982, only 76% of US women had ever used the pill as compared with 82% in 1995 and 2002.60 Past trends in oral contraceptives may account for the observed declines in ovarian cancer incidence. There are currently no recommendations for screening in the general population, but 2 large screening trials are ongoing.61 Because the impact of oral contraceptive use on ovarian cancer risk persists for at least 15 years,62 recent trends in their use will likely lead to continued declines in ovarian cancer incidence in the coming decade.

Leukemia. Leukemia is diagnosed 10 times more frequently in adults, but it is the leading cause of cancer in children aged 0 to 14 years.63 Leukemia is comprised of several diverse types, with few having any identifiable modifiable risk factors.64 Nevertheless, occupational exposures, radiation exposure, chemotherapy, and smoking have all been implicated as risk factors for acute myeloid leukemia, the most frequently diagnosed leukemia.64 It is most reasonable, therefore, to predict that the unchanging rates will continue into the coming decade.

Cancers of the Oral Cavity and Pharynx. The primary modifiable risk factor for oral cancer is tobacco exposure, either by smoking or chewing.65,66 Alcohol is also a factor that works synergistically with tobacco.67 The decline in oral cancer between 1992 and 2004 is likely due to historical reductions in tobacco exposure. Continuing declines are likely in the coming decade.

Pancreatic Cancer. Cigarette smoking is the major risk factor for pancreatic cancers.66,68,69 The importance of other risk factors, including obesity and vegetable intake, is less certain. Despite declining cigarette exposures over the past several decades, rates of pancreatic cancer have remained stable.70 This may be due in part to the more certain diagnosis of pancreatic cancer due to improved diagnostic imaging. Based on the past trends, no substantial change is likely in pancreatic cancer rates in the coming decade.

Kidney Cancer. Increased incidence of kidney cancer has been primarily attributed to small localized tumors identified in patients who undergo diagnostic evaluation for unrelated conditions.71 However, this may not completely explain the increased trend because other factors may also be contributing, including obesity trends,72 as obesity is an important risk factor.47,48 This rising trend in incidence has occurred in spite of decreasing prevalence of tobacco use, a major risk factor for kidney cancer.66 It is expected that the incidence of kidney cancer will continue to rise in the coming decade.

Stomach Cancer. The incidence of stomach cancer has been declining over the past several decades in the United States.73 Declining rates in the historical trends of stomach cancer have been attributed to the nutritional benefits coming from improved food storage and distribution systems and to the declining prevalence of smoking and chronic infection with Helicobacter pylori.74,75 It is likely the long-term historical decline in stomach cancer will continue into the coming decade due in part to declines in smoking prevalence and to declines in the prevalence of persistent Helicobacter pylori infection initiated in childhood among younger cohorts.

Myeloma. Because the etiologic factors for myeloma are not well understood,76 it is most reasonable to project the future rates will remain stable.

Liver Cancer. Liver cancer incidence has been substantially increasing in the past decades.77–79 The primary risk factors for liver cancer include chronic infection with hepatitis B virus and hepatitis C virus, along with excess alcohol and obesity.77–79 The risk of liver cancer is much higher among foreign-born persons, particularly Asian/Pacific Islanders, due to their high rates of chronic infection with hepatitis B virus.80 Despite the initiation of universal infant/childhood hepatitis B vaccination programs for children in the past 20 years,81 only limited effects on hepatocellular carcinoma will be observed by 2015. Based on immigration trends and the epidemic of hepatitis C virus infection, prediction models suggest that liver cancer will continue to rise in the United States over the coming 15 years.82,83

Thyroid Cancer. The incidence of thyroid cancer has been increasing in the United States for the past several decades, primarily due to an increase in small papillary cancers.84 While the increase in small papillary cancers is most likely due to increased detection from improved medical imaging and diagnostic techniques, it is uncertain whether there are any other reasons contributing to this trend.84,85 With increasing numbers of people undergoing neck ultrasound examinations, this trend will likely continue into the future.

Cancers of the Brain and Nervous System. The incidence of brain cancer increased in the 1980s, perhaps due to the advent of better imaging methods for the brain, but rates have been steady in recent years. As little is known about the etiologic factors for brain cancer, it is not possible to confidently predict the trends in the coming decade.86

Cervical Cancer. Invasive cervical cancer is uncommon in the United States because of widespread screening using Pap smears that identify and remove precursor lesions.87 In 2006, the Food and Drug Administration approved a human papillomavirus vaccine for use in girls and women aged 9 to 26 years.88 This vaccine has been shown to be highly effective in protecting against the human papillomavirus serotypes that together cause about 70% of cervical cancer cases.89 Little effect on cervical cancer incidence due to the use of this vaccine will be observed before 2015. Nonetheless, given the historical declining trend and continued high prevalence of Pap smear screening,7 the United States has already surpassed the 25% reduction goal for cervical cancer, and incidence will likely continue to decline, but at a slower rate in the future, as no substantial changes in the prevalence of Pap smear screening are likely.

Esophageal Cancer. The overall incidence of esophageal cancer has remained fairly constant over the past 12 years. However, trends in incidence have been decreasing for the more common squamous cell carcinoma of the esophagus and increasing for adenocarcinoma of the esophagus.90,91 Declines in the rates of squamous cell carcinoma of the esophagus are likely due to declining rates of smoking and alcohol consumption, while increases in adenocarcinaoma of the esophagus are likely due to factors causing acid-reflux disorders of the lower esophagus, especially abdominal obesity.90,91 Due to the trends in tobacco and obesity, it is expected that the past trends of reductions in the more common squamous cell cancer will continue, and increases in adenocarcinoma of the esophagus will also likely continue into the coming decade.

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Performance Measures and Pneumonia Diagnoses: Not So Fast!

Reducing the target time to first antibiotic dose to <4>

Delivering the first antibiotic dose within 4 hours of presentation to patients with community-acquired pneumonia (CAP) is a core quality measure in U.S. hospitals. In an industry-funded study, investigators sought to determine whether such time pressure has affected the accuracy of CAP diagnosis in the emergency department (ED).

The researchers conducted a retrospective analysis of patients who were diagnosed with CAP at a Baltimore ED and admitted to the hospital during one of two periods: from November 2003 through April 2004, when the recommended target time to first antibiotic dose (TFAD) was <8>

The 255 patients admitted under the 8-hour measure were more likely than the 293 patients admitted under the 4-hour measure to have had a discharge diagnosis of CAP (75% vs. 67%; P=0.05) and to have met predefined CAP criteria at admission (46% vs. 34%; P=0.004) and at discharge (62% vs. 54%; P=0.06). Interestingly, the mean TFAD was similar for the two groups — and <3>

Comment: Although limited by its retrospective, single-center design, this study adds to the accumulating evidence that a 4-hour TFAD for CAP is not a valid quality measure. In addition to reducing the accuracy of CAP diagnoses, this measure can lead to inappropriate antibiotic use and its complications (e.g., antibiotic resistance and Clostridium difficile disease). Although the measure has been amended in response to such concerns (the TFAD goal is now 6 hours), the saga of the 4-hour target time should remind us of the "law of unintended consequences" and prompt us to examine future quality measures more carefully before they are widely adopted.

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Migrain tanda awal kerusakan otak?

Pernah mengalami sakit kepala sebagian atau migrain? Mungkin banyak yang menggangap sakit kepala disertai 'aura' (gangguan pandangan yang bisa seperti kilatan cahaya atau bintik-bintik hitam) ini sebagai hal sepele, tapi tahukah Anda, jika migrain bisa membuat sel-sel otak rusak.

Penelitian terbaru menyebutkan mereka yang mengalami migrain beresiko menderita kerusakan otak karena sel-sel otak menggembung dan kurang oksigen. Hasil studi yang dilansir dari Reuters, Senin (30/04) ini turut menjelaskan mengapa penderita migrain memiliki resiko lebih tinggi mengalami stroke.

11/05/2007 - www.kapanlagi.com


Temuan yang diterbitkan dalam Jurnal Nature Neuroscience pekan ini menyebutkan kerusakan otak serupa bisa terjadi karena gegar otak dan kondisi pasca-stroke. Para peneliti menyebutkan penderita sakit kepala sebelah tak boleh sekedar mengkonsumsi penghilang rasa sakit tapi juga harus minum obat yang mencegah migrain.

Studi yang menggunakan tikus sebagai objek ini menunjukkan penggunaan oksigen bisa membantu mengurangi kerusakan otak, kata Takahiro Takano, Maiken Nedergaard, dan rekan dari University of Rocherster, New York, yang menggandeng tim farmasi Denmark, Novo Nordisk.

Mereka mengkaji proses yang disebut depresi penyebaran cortical, yang dikenal dengan sebutan CSD, yakni sebuah gelombang perubahan pada sel-sel yang berkaitan dengan migrain, stroke dan trauma kepala.

Mereka menggunakan mikrosoft dua-photon dan sensor oksigen microelectrodes untuk meneliti otak tikus hidup sementara meneliti proses itu.

Dalam studi tersebut, terjadi pembengkakan dan sel-sel otak jadi haus oksigen. Sel-sel syaraf rusak --terutama dendrites (jaringan tipis dan panjang yang membentang dari satu sel syaraf ke sel syaraf lain).

"Penelitian ini mungkin memiliki dampak klinis langsung, karena beberapa jalur pekerjaan mendukung pendapat bahwa CDS merupakan dasar syaraf migraine dengan aura, dan gelombang spontan CSD mungkin memberi sumbangan pada luka tambahan pada stroke dan luka otak traumatis," papar para peneliti.

Migrain adalah bentuk sakit kapal parah yang membuat orang jadi lemah, dan saat ini telah menyerang 28 juta orang di Amerika.

Dua studi, termasuk satu studi yang disiarkan pekan lalu dalam Archives in Internal Medicine, memperlihatkan bahwa orang yang menderita sakit kepala sebelah lebih mungkin untuk terserang sakit jantung.

Pada studi yang dilakukan pada 2004 lalu dan dimuat dalam British Journal menyebutkan penderita migrain dua kali beresiko mengalami stroke dibandingkan mereka yang tak menderita sakit kepala sebelah. Dalam hal ini perempuan lebih rentan terserang gejala tertentu pada migrain.

Pengobatan nyeri biasa seringkali memiliki dampak kecil pada sakit kepala sebelah tapi salah satu jenis obat yang disebut triptans, yang juga dikenal sebagai serotonin agonists, dan obat ergotamine, bisa digunakan untuk mencegah dampak terburuk jika pasien mengkonsumsi pada saat tanda pertama muncul.

Memberikan lebih banyak dosis oksigen mampu mempersingkat rentang gelombang dampak otak yang terlihat pada CSD, kata para peneliti itu.

Mereka menyatakan migrain dan sejumlah pasien sakit kepala kadangkala dirawat dengan oksigen bertekanan tinggi. Namun tak jelas apakah dampak migrain itu permanen.

Beberapa studi telah menunjukkan dampak itu permanen, sementara yang lain telah memperlihatkan tak ada perbedaan dalam ingatan dan dampak kognitif lain pada pasien migrain. (reuters/rit)

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10 cara agar hidup penuh energi

Hidup bisa naik turun. Kadang merasa semangat, kadang merasa bosan hidup. Ada cara agar hidup tetap berenergi dan bermanfaat bagi kesehatan Anda. Perhatikan faktor berikut yang akan menjamin gaya hidup lebih sehat dan penuh daya hidup.

1. Kelola stres dengan efektif. Stres yang menetap dapat mengikis rasa percaya diri dan energi Anda. Bagaimana pun, ketika stres dikelola secara baik, pikiran dapat bebas berkreasi dan energi pun tidak habis terbuang.
   
   

2. Berolahraga minimal 30 menit setiap hari. Berolahraga menjaga kebugaran tubuh lebih baik dan membantu mempertahankan berat badan ideal. Tanpa olahraga, pikiran menjadi malas.
   
   

3. Kembangkan hubungan yang sehat. Orang bersama teman yang dapat dipercaya dan mempunyai ikatan keluarga yang dekat lebih sedikit kemungkinan untuk sakit dan mereka mengalami penyembuhan yang lebih baik ketika sakit. Memiliki hubungan yang berarti dapat menggairahkan seseorang dalam kehidupan rutinnya.
   
   

4. Ambillah waktu untuk istirahat dan relaksasi yang cukup. Jangan biarkan tekanan seperti rapat, deadline tugas, dan harapan orang lain menguras energi anda. Hindari kelelahan. Lakukan tidur yang rutin dan cukup. Nikmati hari libur di akhir minggu untuk beristirahat dan memperbaharui diri. Liburan tahunan adalah cara yang baik untuk mengisi “baterai kehidupan” kita.
   
   

5. Pertahankan keseimbangan dalam hidup. Ban yang tidak seimbang dapat menyebabkan kendaraan oleng di jalan dengan kecepatan tinggi dan menyebabkan ban rusak. Jadi hidup tanpa keseimbangan dapat membuat anda sedih, stres, dan tegang. Hidup yang seimbang memberikan ketenangan, kedamaian, dan energi baru untuk hidup.
   
   

6. Makanlah makanan kaya antioksidan. Gandum, buah-buahan dan sayuran (terutama yang berwarna) mengandung sejumlah fitokimia yang membantu kesehatan. Kandungan terbanyaknya adalah antioksidan yang melindungi sel-sel dari kanker, penyakit jantung dan penuaan. Pomgranates, bluberry, cranberries dan berry lainnya mengandung kadar antioksidan yang sangat tinggi. Orang yang mengkonsumsi makanan yang kaya serat juga cenderung memiliki lebih banyak energi.
   
   

7. Pelihara spiritual anda berdasarkan keyakinan yang dianut. Mempelajari kitab suci akan menantang pikiran. Melihat bagaimana Tuhan bekerja di masa lalu dapat membangun rasa percaya diri. Kehidupan beragama yang dinamis dan membantu mereka yang membutuhkan akan menggairahkan hidup seseorang.
   
   

8. Menjaga asupan cairan. Bahkan dehidrasi ringan dapat mengganggu sejumlah aspek penting fungsi kognitif seperti konsentrasi, kesadaran, dan memori jangka pendek. Retensi cairan juga dihubungkan dengan peningkatan sakit kepala dan kelelahan, kerusakan pada waktu bereaksi, perhatian, dan koordinasi. Pemberian cairan yang cukup membantu melawan kelelahan dan mempromosikan kesadaran mental.
   
   

9. Jagalah jadwal teratur. Gaya hidup yang tidak teratur dapat menyebabkan seseorang mengalami kehilangan akuitas mental, gangguan konsentrasi, mudah terganggu. Ikuti jadwal yang teratur dapat membantu menjaga mental anda segar dan terjaga.
   
   

10. Proaktif dalam mencegah penyakit. Ambilah tanggung jawab pribadi untk kesehatan anda sendiri. Lakukan pemeriksaan kesehatan dan gigi secara teratur. Anda akan merasa jauh lebih baik ketika anda memiliki kendali terhadap kesehatan Anda.

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