Risk factors for recurrence include tumor size >6 cm cheap zerit 40 mg visa, number of nodules >5 buy zerit without prescription, and vascular invasion per the final pathology report  order zerit with visa. However, a side effect of the ability of the host immune system to recognize and attack “nonself” tissues is rejection of grafted tissues posttransplantation. That side effect was observed clinically for centuries before Medawar demonstrated that it was an intrinsic property of the host immune system in response to foreign tissue . The exogenous modulation of the host immune system to allow sustained graft function has proceeded along with—and often preceded—our understanding of the physiologic mechanism of rejection and tolerance. The immunologic disparity among members of the same species of mammals that leads to lack of recognition of “self” tissue and to rejection of nonself tissue is based on the differences in cell surface molecules that are expressed. The recognition of nonself tissue occurs via two distinct immunologic pathways: direct and indirect allorecognition. Direct allorecognition leads to a more immediate and vigorous immune response against foreign tissue, but, in both pathways, additional helper T lymphocytes are recruited and secrete a wide array of cytokines (e. Then, B lymphocytes begin to secrete antibody directed against the allogeneic tissue in ever-increasing quantities. Rejection mechanistically occurs by infiltration of the graft by effector cells, the binding of antibody, and the activation of complement. Rejection is classified according to the temporal relation between the implantation of the graft and its dysfunction supported by the histologic features seen in allograft. Preformed antibodies directed against antigens presented by the graft mediate activation of complement , activation of endothelial cells, and formation of microvascular thrombi, leading to graft thrombosis and loss . A numerical value, expressed as a percentage, indicates the likelihood of a positive cross- match to the donor population. Most often, such patients were previously sensitized by childbirth, blood transfusions, or prior transplantation. At most centers, heart and liver transplantations are performed without a cross-match, unless the recipient is highly sensitized or has previously received a graft possessing major antigens in common with the current donor (i. Cross-match testing helps clinicians to identify the presence of antibodies against potential donor antigens and to assess the risks of posttransplant rejection and subsequent graft loss. Another research focus is on the similar rapid rejection of xenoreactive antigens that serve as a barrier to the development of xenotransplantation. Rarely, it occurs within the first several days posttransplant, a process termed accelerated acute rejection, most likely a combination of amnestic immune response driven by sensitized memory B lymphocytes and activation of the direct allorecognition pathway. Once challenged by the same donor antigens introduced by the organ transplant, dormant memory lymphocytes reactivate, replicate, and differentiate. Within several days, large numbers of antibodies are directed against the donor allograft resulting in graft rejection. Since the mid-1990s, the use of antibody induction in solid-organ transplant recipients has increased from 25% to more than 90% . Nonetheless, all immunosuppressive agents carry some risk of toxicity and adverse reactions that may complicate therapy (Table 65. Over time, the accumulation of microvascular injury in a graft degrades graft function, with eventual graft loss. This process appears to be mediated by multiple mechanisms, likely including both immune and nonimmune factors. Rarely, tenderness and swelling in the area of the graft occur, and occasionally fever or other signs of systemic inflammation, although such findings used to be common. It is vital to consider alternative diagnoses, particularly in the early postoperative period, including vascular problems with the arterial or venous anastomoses, ureteral obstruction, or urinary leak. Other common causes of apparent graft dysfunction include the acute tubular necrosis associated with delayed graft function, hypovolemia and attendant prerenal azotemia, and the nephrotoxic effects of cyclosporine and tacrolimus. To rule out the vascular and ureteral problems discussed previously, a duplex ultrasound study of the renal graft is commonly obtained. Biopsy is generally safe when performed by an experienced practitioner; however, complications include bleeding, hematoma and arteriovenous fistula formation, and ureteral or major vascular injury. Detect and treat electrolyte abnormalities Drug levels Evaluate for potential drug toxicity Detect inadequate drug levels Blood cell count, Evaluate for cultures potential infection Graft biopsy Firmly establish and grade graft rejection Rejection is graded according to the modified Banff Criteria, which may be used to guide therapy that has been expanded to include C4d negative antibody–mediated rejection . High-dose methylprednisolone (500 to 1,000 mg per day or every other day [2 to 3 doses] is common) is often the initial approach. Hepatic Grafts the transplanted liver is considered to be immunologically “privileged” in that evidence of some degree of immune tolerance occurs in a substantial number of liver transplant recipients over time. Among patients with T-tube drainage (which is increasingly uncommon), the biliary drainage may be seen to thicken, darken, and decrease in amount. Duplex ultrasonography and, in some cases, cholangiography are increasingly being replaced by magnetic resonance imaging. Biopsy findings are classified, according to a standardized set of criteria, as mild, moderate, and severe, with clear implications for prognosis . Clinical findings may include fever and graft tenderness; however, pancreas graft rejection is often clinically silent. For pancreas grafts transplanted along with a renal graft, a rising creatinine level is often used as a surrogate marker of rejection, with antirejection therapy aimed at both the pancreas and the renal allograft. Advantages of a bladder-drained pancreas is the use of a decreasing urinary amylase level as a marker of graft rejection . The diagnosis of pancreas graft rejection is confirmed by biopsy, which may be performed percutaneously or, in bladder-drained recipients, through a cystoscopic, transduodenal approach. Complications (bleeding, arteriovenous fistula formation, graft pancreatitis) have been described, but most biopsies do not lead to complications. Pancreas transplant recipients with early evidence of graft dysfunction should undergo Doppler ultrasonography to rule out graft thrombosis, which occurs in up to 10% to 20% of grafts . High-dose corticosteroids are given initially, with a low threshold maintained for possibly switching to antibody-based therapy, given the relatively common steroid resistance. As a result, biopsy of the intestinal allograft is the gold standard for diagnosis (via ostomy initially). The results have markedly improved over the past two decades: at 1 year, patient survival rates of intestinal transplants alone are >80% and of multivisceral transplants are >70%; the respective graft survival rates are >60% and >50%. Cardiac Grafts Rejection in heart transplant recipients is a significant cause of morbidity and mortality among these patients and accounts for up to a third of the deaths. At one time, the diagnosis was made on the basis of the development of congestive heart failure or the elaboration of electrocardiographic abnormalities. Most centers use frequent percutaneous transjugular right ventricular endomyocardial biopsies as part of a standardized surveillance protocol. Biopsies are evaluated histologically, according to an international grading system , and therapy is directed accordingly. The need for continued endomyocardial biopsies later than 1 year posttransplantation is controversial and center specific, with most choosing to discontinue its performance of biopsies at 1 year unless indicated on clinical grounds. Salvage therapy with an antilymphocyte antibody agent is most common in recipients with histologic findings of more severe rejection, in recipients with steroid-resistant rejection, and in recipients with signs of hemodynamic compromise. Photopheresis has been used in the treatment of recipients with T-cell lymphoma and autoimmune disease. The clinical difficulty posed by rejection is in distinguishing it from other causes of decreased graft function, most commonly infection. A definitive histologic diagnosis of early bronchiolitis obliterans may be difficult to obtain, and so a high degree of clinical suspicion must be maintained.
For typical trisomy 21 buy cheap zerit on-line, the risk of recurrence is the procedure‐related risks of miscarriage for amniocen about 0 order 40mg zerit otc. Robertsonian translocations buy zerit paypal, the recurrent risk is low for de novo events, and is 10–15% if maternally inherited. The posi In a normal pregnancy, both the placenta and the fetus tion of placenta and gestational sac, the fetal sex and the develop from the same fertilized egg. Therefore, theo presence of any markers of structural anomalies should retically, they should all have the same genetic composi be recorded clearly to avoid sampling of the same gesta tion. Mosaicism refers to the presence of two or more tional sac or placenta twice and to allow correct identifi population of cells with different genetic or chromo cation of the abnormal fetus when fetal reduction is somal constitutions in one individual. First Trimester Antenatal Screening 65 trophoblastic chromosomal constitutions are identical Summary box 6. It is a highly accurate screening test for fetal within a maternal plasma sample are sequenced, and then Down’s syndrome, with both sensitivity and specificity compared against the human genome to determine their over 99%. It is a relatively sentation of chromosome 21 is calculated, and compared simple test from the perspective of clinicians and preg against the expected value, or compared against the per nant women. It has been shown that the rela between genes and have no known biological effect. However, there is no evi still lead to a slight increase in the proportion of chromo dence that this approach provides any superiority in some 21 fragments in the maternal plasma. Such small performance as a screening test for fetal Down’s syn difference can be detected using the latest molecular drome. This method is not suitable in maternal plasma is from the trophoblastic cells of the for donor egg pregnancies, and may not be feasible in placenta. All relevant clinical data are either lacking or limited and published studies on cost‐effectiveness support the use of will not be elaborated further here. However, placental mosaicisms and lower levels of maternal mosa most published studies include pregnant subjects at 12 icisms than conventional screening tests, which could weeks or beyond. It is possible that the detection rate may be lower in the first trimester, by about 1. The only barrier for its clinical use at present is the relatively high cost in most countries. If pregnancy is at or after 15 weeks, amniocentesis should However, there is no reason why pregnant women can be the diagnostic method of choice. This allows earlier diagnosis and interven tial or contingent manner at their own cost. Delaying to 15 weeks for an amniocentesis could detection rate, which is limited by the primary screening be psychologically stressful during the period of waiting, test. This approach will be useful to those who are satis but this approach will completely avoid the possibility of fied with the detection rate of the traditional screening trisomy confined to the placenta resulting in termination tests, but would like to avoid invasive tests as much as of a normal fetus. But such sources of false positives must be Confirmatory test is essential considered during the post‐test counselling and when making a decision for the type of diagnostic test. The from an underlying malignancy; and (vi) false positive decision to continue with pregnancy is common even with related to the nature and limitation of the technology. The true detection rate is uncertain because Fetal fraction is obviously an important factor. Fetal many of the affected individuals are asymptomatic at fraction is negatively correlated with maternal weight, birth. The fetal fraction some may have problems with fertility, ambiguous geni was found to be below 4% in 0. The laboratory cost for the additional showed that false‐negative cases had a significantly lower bioinformatics analysis and reporting is minimal. Therefore, the additional infor mation on other chromosomes may be clinically important. Therefore, the risks and benefits of dis somy 21 detection in twin pregnancy may be lower than closing information about other chromosomes need to in singleton pregnancy but is likely to be 95–99% with be carefully considered. This application is rapidly changing and is or offered to those with twin pregnancies. A first‐trimester scan should be part of the cases for various reasons; the figure is approximately screening package. In general, screen ing using single markers does not produce adequate sen sitivity for routine clinical use. Recent studies have First‐trimester screening of fetal suggested that risk assessment based on algorithms com structural anomalies bining previous obstetric and medical history, personal demographic data, sonographic signs and biochemical Approximately 60% of major structural abnormalities markers may be an effective screening tool . Further can be diagnosed in the first trimester of pregnancy, such details will be discussed under specific conditions. The poten tial benefit is an earlier diagnosis which will provide more time for the couple to undergo further tests and to consider further management plans, allow early inter First‐trimester screening of single vention including pregnancy termination, and possibly gene disorders lead to better outcome or less physical or psychological trauma. This will certainly become rou However, there are many potential problems that need to tine in the near future when the cost becomes more be considered. In 1) the detection rate of fetal anomalies in the first tri reality, most pregnant women do not have a proper pre‐ mester can never reach that of second‐trimester scan. For further details, must be explained clearly to the pregnant women to refer to Chapter 4. An almost complete fetal morphological assessment is usually feasible Conclusion towards the end of 13 weeks of gestation, but is much more technically challenging at 11 weeks of gestation. The technology is may not be feasible after pregnancy termination, rapidly evolving, and is being expanded rapidly to cover especially if a surgical method is used. By the time this book is published, some of the that require further evaluation and assessment when the details stated here might have become outdated. This may result in signifi However, the principle remains that pregnant women cant psychological stress and emotional disturbance. Am J Med performance of first‐trimester nuchal translucency for Genet A 2009;149A:2716–2722. First thickness and normal karyotype: time for parental trimester serum markers stability during sample reassurance. Ultrasound Obstet Gynecol transportation from the obstetrical site to the screening 2007;30:11–18. Non‐invasive First‐trimester screening for trisomy 18, 13, triploidy prenatal testing for fetal chromosomal abnormalities and Turner syndrome by a detailed early anomaly scan. Ultrasound Obstet Gynecol mosaicism in chorionic villi: results of a monocentric 2014;43:254–264. Fetal fraction in maternal plasma 9 Akolekar R, Beta J, Picciarelli G, Ogilvie C, D’Antonio F. Ultrasound Obstet amniocentesis and chorionic villus sampling: a Gynecol 2013;41:26–32. Ultrasound Obstet Gynecol 4‐week‐pregnant women following in vitro fertilization 2015;45:530–538. Scientific endeavours to mates indicate that over 30 000 women die worldwide determine these elusive vasoactive factors have largely each year because of pre‐eclampsia and its complica- been responsible for pre‐eclampsia being known as the tions, with 98% of these occurring in developing coun- ‘disease of theories’. Globally, pre‐eclampsia has been estimated to Several candidates have been considered in the role of cause between 10 and 25% of perinatal loss [2,3].
Pituitary Adenoma Study Group order zerit 40mg with visa, Pitu- and Steroid Hormone Contraception cheap 40 mg zerit fast delivery, itary adenomas and oral contraceptives: Cardiovascular disease and use of oral a multicenter case-control study order generic zerit pills, Fertil and injectable progestogen-only con- Steril 39:753, 1983. Hulting A-L, Werner S, Hagenfeldt K, Oral Contraceptives and the Health of Oral contraceptives do not promote the Young Women, Eur J Contracept Reprod development or growth of prolactino- Health Care 4:67, 1999. Wolner-Hanssen P, Oral contracep- asis, and bacterial vaginosis, Am J Obstet tive use modifies the manifestations of Gynecol 163:510, 1990. Potter L, Oakley D, de Leon-Wong M, A randomized controlled trial of sec- E, Cañamar R, Measuring compliance ond- versus third-generation oral contra- among oral contraceptive users, Fam ceptives in the treatment of acne vulgaris, Plann Perspect 28:154, 1996. Westhoff C, Jones K, Robilotto C, Schumacher U, Gräser T, Efficacy of a Heartwell S, Edwards S, Zieman M, combined oral contraceptive containing Cushman L, Smoking and oral contra- 0. Vessey M, Metcalfe A, Wells C, trolled trial, Obstet Gynecol 112:563, McPherson K, Westhoff C, Yeates C, 2008. Tzourio C, Tehindrazanarierelo A, ment with a fluoroquinolone (ofloxacin), Iglésias S, Alpérovitch A, Chgedru F, Adv Contracep 12:101, 1996. Bounds W, Guillebaud J, Observational spective study of reproductive factors series on women using the contraceptive and oral contraceptive use in relation to Mirena concurrently with anti-epileptic the risk of uterine leiomyomata, Fertil and other enzyme-inducing drugs, J Fam Steril 70:432, 1998. Vessey M, Painter R, Yeates D, Oral Influence of oral contraceptive therapy contraception and epilepsy: findings in a on the activity of systemic lupus erythe- large cohort study, Contraception 66:77, matosus, Arthritis Rheum 25:618, 1982. Vessey M, Jewell D, Smith A, Yeates D, kidney transplantation, Transplant Proc McPherson K, Chronic inflammatory 39:2759, 2007. Jabiry-Zieniewicz Z, Bobrowska K, of oral contraceptives: findings in a large Kaminski P, Wielgos M, Zieniewicz cohort study of women of childbearing K, Krawczyk M, Low-dose hormonal age, Br Med J 292:1101, 1986. Katschinski B, Fingerie D, Scherbaum ceptives on delayed onset muscle sore- B, Goebell H, Oral contraceptive use and ness following exercise, Contraception cigarette smoking in Crohn’s disease, Dig 56:59, 1997. Larsson G, Milsom I, Lindstedt G, Rybo Zieniewicz Z, Kaminski P, Wielgos M, G, the influence of a low-dose combined Oral Contraception oral contraceptive on menstrual blood Influence of oral contraceptive use on loss and iron status, Contraception bone density in climacteric women, 46:327, 1992. Tuppurrainen M, Kröger H, Saarikoski Tozzi L, Rubessa S, La Vecchia C, Con- S, Honkanen R, Alhava E, the effect traceptive methods and risk of pelvic en- of previous oral contraceptive use on dometriosis, Contraception 49:47, 1994. Gambacciani M, Spinetti A, Taponeco among parous women, Obstet Gynecol F, Cappagli B, Piaggesi L, Fioretti P, 85:983, 1995. Harada T, Momoeda M, Taketani Y, pausal vertebral bone loss: effects of a Hoshiai H, Terakawa N, Low-dose oral low-dose oral contraceptive preparation contraceptive pill for dysmenorrhea as- on bone mineral density and metabo- sociated with endometriosis: a placebo- lism, Obstet Gynecol 83:392, 1994. Hartard M, Bottermann P, Bartenstein Oral contraceptive use, reproductive his- P, Jeschke D, Schwaiger M, Effects on tory, and risk of epithelial ovarian cancer bone mineral density of low-dosed oral in women with and without endometriosis, contraceptives compared to and com- Am J Obstet Gynecol 191:733, 2004. Mallmin H, Ljunghall S, Persson I, fluence of oral contraceptive use on bone Bergstrom R, Risk factors for fractures density in climacteric women, Maturitas of the distal forearm: a population-based 9:375, 1988. Johansson C, Mellström D, An earlier bone mass in pre- and post-menopausal fracture as a risk factor for new fracture women, Contraception 34:333, 1986. Enzelberger H, Metka M, Heytmanek menopausal age in women, Maturitas G, Schurz B, Kurz C, Kusztrich M, 24:97, 1996. MacKenna A, Fabres C, Alam V, Cats A, Reduction of the risk of rheu- Morales V, Clinical management of matoid arthritis among women who take functional ovarian cysts: a prospective oral contraceptives, Arthritis Rheum and randomized study, Hum Reprod 33:173, 1990. Emergency Postcoital Contraception The use of a method afer intercourse to prevent pregnancy is commonly called postcoital contraception, or the “morning afer” treatment. It is an important option for patients, and should be considered when condoms break, sexual assault occurs, if diaphragms or cervical caps dislodge, or with the lapsed use of any method. In studies at abortion units, 50% to 60% of the patients would have been suitable for emergency contraception and would have used it if readily available. Availability should be favorably infuenced in the United States by the recent Food and Drug Administration approval making levonorgestrel emergency contraception available without a prescription to women older than age 16. Women who have used emergency contraception are very satisfed with the method, and most importantly, do not express an intention to substitute this method for regular contraception. The initial work in monkeys led to the use of high doses of diethylstilbestrol (25 to 50 mg/d) and ethinyl estradiol in women. Yuzpe developed a method utilizing a combination oral contraceptive, resulting in an important reduction in dosage. Lo Ovral, Nordette, Levlen, Triphasil, Trilevlen: four tablets followed by four tablets 12 hours later. The Method of Choice for Emergency Contraception is Levonorgestrel Alone Levonorgestrel in a dose of 0. In some countries, a kit (Preven) is also available containing four tablets, each containing 50 mg ethinyl estradiol and 0. Clinicians should consider providing advance information and a pre- scription or an emergency contraceptive kit to patients (a kit can be a sim- ple envelope containing instructions and the appropriate number of oral contraceptives) to be taken when needed. It would be a major contribution Special Uses of Oral Contraception to our eforts to avoid unwanted pregnancies for all patients without contraindications to oral contraceptives to have emergency contraception available for use when needed. In our view, this would be much more efec- tive in reducing the need for abortion than waiting for patients to call. In studies of self-administration, adult women in Scotland and younger women in California increased the use of emergency contraception without adverse efects such as increasing unprotected sex. Efcacy has been confrmed in large clinical trials and summarized in complete reviews of the literature. In general clinical use, the method with oral contraceptives can reduce the risk of pregnancy by about 75%; this degree of reduction in probability of conception (given the relatively low chance, about 8%, for pregnancy associated with one act of coitus)37 yields the 2% failure rate measured in clinical studies. Careful assessment of the reported experience with emergency contraception indi- cated that the method is equally efective when started on the frst, second, or third day afer intercourse (which would allow user-friendly schedul- ing), and that efcacy extends beyond 72 hours. For this reason, the treatment should be initiated as soon as possible afer sexual exposure, an important argument in favor of advance provision. We should emphasize, in case the patient is already pregnant, that there is no evidence that exposure to the amounts of estrogen and progestin in oral contraceptives is an abortifacient or teratogenic. A delay in menses afer treatment warrants testing for pregnancy and consideration for the possibility of an ectopic pregnancy. Side efects refect the high doses used: nausea and vomiting, 50% and 20% with estrogen-progestin oral contraceptives, but only 18% and 4% with levonorgestrel. If a patient vomits within an hour afer taking pills, additional pills must be administered as soon as possible. Nausea and vomiting are experienced at such a lower rate with the levonorgestrel-only method that an antiemetic is not necessary. General Practice Research Database could fnd no evidence for an increased risk of venous thromboembolism with the short-term use of oral contraceptives for emergency contraception (indeed, no cases were found for as long as 60 days afer use in more than 100,000 episodes of use). For women with a contraindication to exog- enous estrogen, the progestin-only method with levonorgestrel should be used for emergency contraception. The levonorgestrel-only method is the treatment of choice anyway because of greater efcacy and fewer side efects. A 3-week follow-up visit should be scheduled to assess the result and to counsel for routine contraception. Even better, a method of contraception should be initiated immediately afer the use of emergency contraception to avoid an unwanted pregnancy. A norethindrone-ethinyl estradiol combination was found to be equally effective to the levonorgestrel-ethinyl estradiol formulation, and it is likely that any combination oral contraceptive would be successful. Mifepristone in a single oral dose of 600 mg is associated with markedly less nausea and vomiting than with oral contraceptives and an efcacy rate of nearly 100%. In randomized trials, 10 mg mifepristone was as efective as 25, 50, or 600 mg, preventing about 80% to 85% of expected pregnancies (the same ef- cacy and side efects as with the levonorgestrel method), with a slight decrease in efcacy when treatment was delayed to 5 days afer intercourse.
Measurement of this dimension zerit 40mg for sale, while difficult buy zerit 40mg, may be worthwhile as there is some evidence that variations in culture are linked to clinical outcomes  buy zerit 40 mg cheap. First, reports have been generated in a punitive environment that focuses on the provider who committed an error rather than on systems of care, and thus discourages self-reporting of errors . Second, each report of an error represents a “numerator” value that does not give insight into the denominator pool of patients at risk of similar errors. Third, definitions of errors used by incident reporting systems vary, which impedes data synthesis, analysis, collaborative work, and evaluation of the impact of changes in healthcare delivery . And fourth, appropriate functional data spanning the domains of structure, process, and outcome are not collected, which impedes the ability to “deconstruct” an error to understand its root causes and patient impact. Internet-based systems allow anonymous reporting of errors, encouraging providers who have either committed an error or have knowledge of an error to enter related information into a central data repository . Institutional commitment to a “culture of safety” has a motivational effect on error reporting because healthcare providers recognize that “someone is listening. This culture requires several essential process elements to enhance error reporting: A team (a) convenes to develop preventative solutions to a reported error, (b) generates plans to improve the care, and (c) has a method for implementing and measuring the impact of their plan . The taxonomy used was designed to conform to an analytical framework and common word usages to promote its use and the understanding of its output. Data entered allows classification of a patient safety event within five complementary primary groups: impact—the outcome or effects of medical error and systems failure, commonly referred to as harm to the patient; type—the implied or visible processes that were faulty or failed; domain—the characteristics of the setting in which an incident occurred and the type of individuals involved; cause—the factors and agents that led to an incident; and prevention and mitigation—the measures taken or proposed to reduce incidence and effects of adverse occurrences. These systems describe events with a multidimensional taxonomy to facilitate the comprehensive description and full deconstruction of errors to determine their root causes . However, even if the taxonomy issues of incidence reporting are improved, the problem of determining the true incidence rate remains. A comprehensively described and deconstructed incident only gives insight into the numerator; it does not provide information on the number of patients at risk and does not allow determination of true incidence rates. The denominators are especially difficult to determine because these measurements have major impacts on interpretation ; for instance, C. The numerator data are equally challenging because of the time and expense of chart extraction needed for their collection. If the characteristics of the patient population change over time, then these factors must be accounted for as well. For example, if the patient population changes or new services such as transplantation are offered by a given hospital, then the patient mix will change and adjusted hazard rates will be needed. Although most of these indicators relate to surgical patients, newer indicators are being designed to measure the safety of care for medical patients with critical illnesses, such as myocardial infarction, stroke, and congestive heart failure. Although this method is powerful and can be quite useful, it is important to also recognize its limitations. Large data sets such as these also have limited data quality for clinically relevant covariates, so controlling for confounders is difficult. Because all of the clinically relevant covariates are not included, the problem of residual confounding is always a problem and caution should be exercised when interpreting results. Making interinstitutional comparisons is therefore difficult, and even when trending data over time, results must be analyzed with caution. When there is marked heterogeneity in terms of clinical problems and rapid changes in process of care over time, this approach will face difficulties. However, it may be difficult to isolate and ascertain the contributory effect of influential factors, such as adherence to best practice by the caregiving team, the role of complications, or level of care. Physicians and other clinicians often have a stronger sense of accountability toward a process measure than an outcome measure because the process measure can be more strongly linked to a particular care provider or team behaviors . Physicians may also believe that outcomes can be overly influenced by severity of disease and prove resistant to quality improvement efforts. To serve as an accurate measure of safety and to influence quality improvement, process measures must have a causal relationship with the outcome they intend to represent. Computerized physician order entry (order- sets) for drugs has the potential to decrease the rate of serious medication errors  and to improve clinical outcomes when applied to antibiotic prescribing . Process of care measurement is often very effective for certain types of problems (like computerized order entry), but it is important to recognize some of the limitations and difficulties inherent in this system when applied to more complex problems. When strong evidence-based clinical practice guidelines are available, it is a feasible strategy, but often this is not the case. In addition, properly identifying those patients eligible for a particular protocol during the appropriate time period is critical. Determining the numerator for such process of care measures is fairly easy (who actually received the drug), but determining the denominator can be more difficult and can be costly because of the time and expense needed for data collection (e. In addition, chart abstraction in such cases usually requires a high level of expert judgment, which makes it variable, difficult, and costly. Thus, process of care measurement, because of cost and time considerations, may be a suitable approach to improving safety for those problems in which there is a strong evidence base and for which the costs of identifying the patient population (both numerator and denominator) are sustainable and warranted by the value of information obtained. Additional structure measures of safety include the presence of resources to establish ongoing competency of medical staff and residents , adequate nurse staffing and skill sets [40,41], and appropriate technology resources, such as smart pumps and bar coding . Pronovost and Sexton  recommend measuring the entire hospital annually with the full Safety Attitudes Questionnaire that has construct validity and sufficient reliability for measuring the single construct of safety culture. Trigger Tools Trigger tools refer to techniques used to detect organizational signals for adverse events. For instance, orders for flumazenil may identify patients who were given an overdose of a benzodiazepine drug. A trigger or set of triggers can be used to identify medical records for retrospective review to assess organizational safety, or used in “real time” as a tool to identify a specific patient at risk of an adverse outcome. Limitations of Existing Metrics and Their Applications Currently, the majority of data collected to measure safety is process oriented. However, there is only limited evidence that the use of current process measures translates into better outcomes [48,49]. In addition, risk adjustment to facilitate valid comparisons increases the amount and complexity of data abstraction required, further increasing costs. In such instances, proper measures require collecting information on a very large population, which constitutes the denominator of the rates being measured. It is also very important to consider carefully the attributes of performance measures and how the measures are arrived at. In addition, the magnitude and direction of bias for reporting can be greater than the true variation of outcomes. This is because most reporting systems, such as the Patient Safety Reporting System, provide data from a non-randomly selected sample and the population at risk is not known. When interpreting safety metrics, careful attention must be paid, bias must be considered, and all results should be viewed with caution. There are a variety of endorsed quality and safety measures currently available, some with a stronger evidence base than others, but which ones are best is not clear and will depend largely on local factors. The cost- effectiveness of even the best evidence-based measures and interventions is difficult to prove, and the potential benefits of implementation are likely to vary depending on the local context. The National Quality Forum measures for quality in intensive care serve to highlight some of the difficulties encountered.
L. Norris. University of Rio Grande.