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Jehovah's Witness Informed Consent

Autonomy, Informed Consent and the Death of Therapeutic Privilege: Lessons Learned from the Jehovah’s Witnesses

An Independent Learning Module for Health Care Workers

Authors

 * D. John Doyle MD, PhD, FRCPC, June 21, 2005, djdoyle@undefinedhotmail.com

Purpose of This Learning Module
The purpose of this learning module is to bring readers up to date with some of the more important issues regarding informed consent and patient autonomy, which are discussed from clinical, ethical and legal perspectives. A synopsis of the problem of clinical informed consent is presented, touching on both the ethical and legal issues as well as the various “standards” of consent. The idea that the process of informed consent may occasionally itself be a health hazard is presented. The notion of therapeutic privilege, a concept declining in acceptance, is also discussed. Finally, old and new developments regarding autonomy and informed consent in Jehovah’s Witness patients are discussed.

Specific Learning Objectives
The specific learning objectives for this module are as follows: (1) to understand the philosophical notions of informed consent and patient autonomy, and the relationship between them, (2) to identify the various clinical situations where full informed consent may not be possible, (3) to identify possible clinical situations where informed consent may not be in the interests of the patient’s health, (4) to understand the notion of “therapeutic privilege”, (5) to identify possible clinical situations where conflicting ethical principles which may lead to disagreement between health care workers and patients, (6) to examine several noteworthy legal rulings in the USA and Canada related to autonomy and consent of which health care workers should be aware, and (7) understand how issues related to the care of the Jehovah's Witness patient has influenced our notions of autonomy and consent.

Introduction
Autonomy is one of the four guiding principles of the “Georgetown School” of bioethics, the other principles being beneficence, justice and nonmalfeasance (Beauchamp and Childress 1994). Autonomy implies the right to actively participate in medical decisions concerning oneself without being dictated to or controlled by other parties. Central to the concept of autonomy in this setting is the requirement that a patient understand the various clinical choices available and the risks and benefits associated with those choices. In other words, informed consent is a necessary condition for patient autonomy.

This notion of autonomy implies that individuals should be given adequate means to make their own decisions - decisions made based on their personal value system. This also implies that patients must be provided with appropriate information to make informed decision-making possible. The information that should be supplied to establish clinical informed consent usually focuses on the nature, risks and benefits of the proposed intervention with a discussion of the alternatives to the planned intervention, including their associated risks, benefits, and uncertainties.

Obtaining informed consent also entails ensuring that an adequate degree of patient understanding exists. Thus the clinician must also establish that the patient has sufficient decision-making competence for informed consent to be possible. This is usually accomplished informally, by considering whether the patient appears to comprehend the information presented and establishing that the patient can discuss the issues with caregivers in a reasonable and logical manner. In some cases, however, formal psychological consultation is requested.

Three approaches to the issues of providing informed consent have been described: (Edwards 1999):

• “reasonable physician standard: what would a typical physician say about this intervention? This standard allows the physician to determine what information is appropriate to disclose. However, it is probably not enough, since most research in this area shows that the typical physician tells the patient very little. This standard is also generally considered inconsistent with the goals of informed consent as the focus is on the physician rather than on what the patient needs to know.”

• “reasonable patient standard: what would the average patient need to know in order to be an informed participant in the decision? This standard focuses on considering what a patient would need to know in order to understand the decision at hand.”

• “subjective standard: what would this patient need to know and understand in order to make an informed decision? This standard is the most challenging to incorporate into practice, since it requires tailoring information to each patient.”

In recent years Canada and many states in the USA have adopted the “reasonable patient” standard as their legal model. It is interesting to note that under this model the requirement for informed consent does not necessarily require that the patient be supplied with every imaginable detail. For instance, in a 1980 Canadian Supreme Court decision [Reibl v. Hughes [1980] 2 SCR 880] the court decided that both minuscule risks associated with devastating outcomes (e.g., stroke, death) as well as common but minor risks (e.g., damage to teeth with tracheal intubation) must be disclosed to the patient, but that a detailed disclosure of all possible risks is not a legal requirement.

Therapeutic Privilege
The notion of "therapeutic privilege" refers to the withholding of important information by the clinician during the “consent” process in the belief that disclosure of such information would lead to the harm or suffering of the patient (Meisel et al. 1977). The philosophical basis for "therapeutic privilege" is the notion that beneficence should take precedence over autonomy in cases where a conflict between these two principles exists. Today, with the collapse of paternalism in modern clinical care, and with the widespread adoption of the “reasonable patient” model for legal informed consent, therapeutic privilege is invoked only rarely. This is so both as a result of medico-legal prudence and in response to modern cultural shifts. Furthermore, some clinicians argue that if a person feels that providing a patient with relevant clinical information may be so upsetting to the patient as to cause extreme psychological harm, the patient should be assessed for mental competency.

Still, therapeutic privilege has its cautious supporters. For instance, Etchels et al. (1996), discussing the Canadian situation, make the case that therapeutic privilege may sometimes be appropriate. They write:

The need for sensitivity to cultural norms may potentially support the exercise of therapeutic privilege. In some cultures therapeutic privilege is widely invoked, and it is unclear whether patients from these cultures should always be subjected to Western standards of consent. However, given the legal status of therapeutic privilege in Canada, clinicians should avoid invoking therapeutic privilege. It is better for the clinician to offer information and allow the patient to refuse or accept further disclosure.

Further complicating the issue of informed consent is the recognition that there are a number of circumstances where ensuring that the requirements for full informed consent can be problematic. Such situations include (1) the premedicated patient, (2) the parturient in labor, (3) the “psychologically fragile” patient under enormous emotional stress, (4) the patient with known mental illness, (5) the patient with organic brain disease, (6) the immature adult patient, and (7) the hostile and distrustful patient who is angry at the world and places absolutely no trust in authority figures.

There is also an additional consideration to ponder. Some clinicians would maintain that the process of informed consent has health risks in and of itself, and that these risks should be weighed in discussions of the informed consent process. In particular, consider the case of the patient who is impaired at making judgments involving clinical risk management and who refuses a reasonable intervention involving a relatively small risk even though it would substantially eliminate another, much larger, clinical risk.

The following (edited) posting by a doctor working in the “clinical trenches” illustrates the matter:

I feel that the process of informed consent is not always in the patient's best interests. Many patients clearly need cardiac catheterization and initially agree. But once I inform them of the risks of the procedure, they then refuse. Even when I subsequently inform them that the risk of not doing the procedure is far greater, they persist in their refusal. Thus the process of informed consent has caused the patient to act in a manner deleterious to their health. Many patients cannot understand the concept of risk/benefit ratios. I understand that we wish to avoid medical paternalism and promote patient independence but medical decision making is not the same as a consumer pulling products off a store shelf. Part of what the patient is paying for is our professional judgement.

Another example concerns the administration of blood transfusions. In my own clinical practice as an anesthesiologist, I frequently administer blood transfusions, particularly during surgical procedures with severe blood loss. In fact, anesthesiologists give more than 50 per cent of the nation's blood supply to correct for blood loss during and after surgery. And, associated with every "unit" (about 250 mL) of blood given is a small, but definitely not trivial, chance of transmitting infection or getting some other complication.

I find the decision about giving or not giving blood particularly difficult when a patient asks me to promise not to transfuse during surgery, but has no reason for this request other than an exaggerated fear of becoming HIV infected. So far, I have always been able to convince such patients to allow me to give blood if it is absolutely necessary, usually by asking them about what they would want me to do in the very rare event of unexpected massive blood loss. Typically their response is, "Well, I would die unless I got blood, so of course..."

What should I do, however, if I can't convince a patient to permit me to give blood to save his or her life? One option is to respect the patient's decision. Yet I'm uncomfortable with this position. My discomfort arises from the fact that such people are not making sound judgments about the current risks involved in blood transfusion. Frightened by reports of past blood-transfusion tragedies, people today are inflating the very small risk if HIV or other infection that actually exists. In such an atmosphere of fear, they are making ill-informed decisions about their own health care, decisions by which I fear I must abide.

How Much Information?
It was noted earlier that informed consent under the “reasonable patient” standard does not necessarily require that the patient be supplied with every imaginable detail. Still, there are exceptional patients who ask for far more information than usual. While this may reflect reluctance for the patient to relinquish control, it may also indicative of an analytical coping style in an intelligent, curious patient. My approach to such patients is to systematically provide detailed answers to all questions asked, including pointing out those circumstances where there is no well-established answer to a question because of existing limits to medical knowledge. Also, many patients are familiar with using PubMed and other resources to get information via the Internet, and this too can serve as a means for some patients to get additional information.

Still, some questions may be out of bounds to some practitioners. For instance, some surgeons might be reluctant to disclose the details of their complication rates, or may not even have such information specifically tabulated. As a more extreme example, it would not be considered reasonable to allow a patient considering a particular surgeon to conduct his or her own private chart review of the last 100 cases carried out by that surgeon so as to obtain useful information.

Many health consumers use the Internet to obtain physician profile information, including malpractice claim data. A number of US states now put malpractice data on the Internet. For instance, the State of Virginia makes practitioner information available at http://www.vahealthprovider.com, while the Federation of State Medical Boards of the United States offers a national fee-based service at http://www.docinfo.org. Finally, the Questionable Doctors site at http://www.questionabledoctors.org “contains data on disciplinary actions taken for medical incompetence, misprescribing drugs, sexual misconduct, criminal convictions, ethical lapses and other offences.”

Although many physicians embrace this idea in theory, many are worried about the use of malpractice information as an indicator of competence or quality. Cynics argue that the medico-legal systems in Canada and the USA are so haphazard that good doctors are just as likely to be sued as those who may be practicing below the standard of care. Other opponents of this concept contend that the public may misinterpret malpractice history data and punish capable doctors who happen to treat a large number of high-risk patients.

Drawing on the Jehovah’s Witnesses Experience
A patient has a legal right to decide to forgo “clinically necessary” treatment if the patient is judged to be competent to make that decision. No where is this better illustrated than in the case of the Jehovah’s Witness patient. There are approximately seven million Jehovah’s Witnesses world-wide, with approximately one million in the USA and about one hundred eighty four thousand in Canada. The Jehovah's Witnesses are a Christian religion whose followers believe the Bible to be the true and literal word of God whose name is Jehovah and whose son, Jesus Christ, established true Christianity. Witnesses view Jehovah God as the ultimate moral authority and do not salute flags, join service organizations, enlist in the military, vote in public elections, or take an interest in civil government.

Traditionally, orthodox Jehovah’s Witnesses will not accept homologous or autologous whole blood, packed red blood cells, plasma, platelets and white blood cells, even when “clinically necessary” (Letsoalo 1998, Ridley 1999). The determination that blood transfusions were a violation of God's law was made in 1945 and is primarily based on three biblical passages: Genesis 9:3,4; Leviticus 17:10-16; Acts 15:28, 29.

This prohibition can result in a challenging dilemma for physicians because a routine, safe, and potentially life-saving medical intervention is unacceptable to the patient (Benson 1989, Rothenberg 1990, Mann et al. 1992). Anesthesiologists are particularly affected because they are almost always responsible for intraoperative transfusion management. This sometimes puts anesthesiologists and other clinicians in highly unusual clinical situations (Harnett et al. 2000, Baldry et al. 2000).

It should come as no surprise that this situation has resulted in a number of legal debates, and most legal issues concerning the medical care of Jehovah's Witnesses center on the issues of autonomy and consent. In Canada, the landmark legal case regarding the clinical care of Jehovah's Witness patients was the case of Malette v. Shulman [Malette v Shulman (1990), 37 OAC 281 (CA)]. The courts established that clinicians should not administer emergency treatment without consent if they have reason to believe that the patient would refuse such treatment if he or she were capable. In this case, Dr. Shulman administered a blood transfusion to a patient who was unconscious as a result of hypovolemic shock. The patient carried a signed (but undated and unwitnessed) wallet card indicating that she was a Jehovah's Witness and did not want to receive blood transfusions under any circumstances. Despite this, blood was transfused out of clinical necessity. Although the transfusions were almost certainly responsible for saving the patient's life, the court found the clinician liable for battery. The judge stated: “To transfuse a Jehovah's Witness in the face of her explicit instructions to the contrary would, in my opinion, violate her right to control her own body and show disrespect for the religious values by which she has chosen to live her life.”

In the USA, the case that established the competent adults right to refuse treatment occurred in 1914 in Schloendorff vs. Society of New York Hospital. (Schloendorff vs Society of New York Hospital, 105 N.E. 92, (1914).) A woman agreed to an examination under anesthesia but refused consent for surgery. Despite this, surgery was performed, and serious unexpected complications followed. A lawsuit was launched and resolved in favor of the plaintiff. The presiding judge stated that "Every human being of adult years and sound mind has a right to determine what shall be done with his own body". Despite this ruling the patient lost her case because the hospital was a charitable institution and was consequently immune from liability. Still, the case established the notion of informed consent and of the right of a competent adult patient to choose or refuse treatment. Since the time of the Schloendorff case a large number of American legal decisions have reinforced the right of a competent adult to choose his or her treatment, even when the decision is not medically sound.

A particularly unusual legal case occurred in Pomona, California where a drunken driver rammed his pickup truck into a stationary car, injuring a 55 year old Jehovah’s Witness woman standing by the side of the road (http://www.religiontoday.com/Archive/ NewsSummary/ ). She refused a needed blood transfusion, and consequently died in hospital. Prosecutors said the driver was responsible for the death because he caused the injuries and he was convicted of manslaughter. His lawyers argued that the immediate cause of the woman’s death was her refusal of a blood transfusion, since she very likely would have lived had a blood transfusion been carried out.

Dissent and Consent - The Jehovah’s Witness “Reform Movement”
Since 1996, a number of Jehovah’s Witnesses have anonymously expressed their dissent to the Jehovah’s Witness blood policy and formed a group called the Associated Jehovah's Witnesses for Reform on Blood (AJWRB), with a Web presence at www.ajwrb.org. Their goal is for a “reformation” of existing blood policy, which they see as a “complicated web of contradictory rules and conditions strictly enforced without biblical basis”. Their actions are for the most part conducted anonymously, since experience shows that for a Jehovah’s Witness to express any criticism often results in expulsion from the church (ecclesiastical disfellowshipping). The existence of this movement presents an ethical dimension that I discuss next.

It was implied earlier that the central ethical dilemma in the management of Jehovah’s Witness patients is in the nature of a conflict between beneficence and autonomy, where autonomy is generally given precedence over beneficence, at least in American and Canadian law. But there is another potential dilemma for anesthesiologists who care for Jehovah’s Witness patients: because many Jehovah’s Witness patients are not likely to be fully informed about possible inconsistencies in church doctrine regarding medical issues, should anesthesiologists attempt an in-depth discussion to encourage a rational and truly autonomous decision (for instance, using information provided by the Jehovah’s Witness “reform” movement [www.ajwrb.org]), or should they remain silent regardless of the degree to which they might find the patients’ views to be irrational and misguided, so as to avoid the perception of “religious interference”.

Muramoto (1998a, 1998b, 1999, 2000) and others (Savulescu 1995, Doyle 1998, Elder 2000) have taken the position that truly ethical physicians should inform their patients as fully as possible on all matters affecting their care, seeing any discussions centering on possible religious inconsistencies as merely an attempt to ensure that their patients have the opportunity to be fully informed on an important life-and-death issue. By contrast, Shander (1999) has taken the position that one should remain silent on religious issues and focus on purely clinical concerns, citing the difficulties of what he sees as essentially being an attempt at religious conversion. In short, Shander believes that the anesthesiologist has no business influencing a person’s religious views.

This is not a simple issue since, given that the leaders of the Jehovah’s Witness faith have reversed previous teachings against medical interventions such as vaccination and organ transplantation, and given that some blood products such as albumin, immunoglobulins and clotting factors are already allowed (according to an individual’s conscience) (Bergman 1994), some Witnesses believe that it is only a matter of time and effort before the ban against blood transfusions is removed completely.

The situation is obviously complex and rich in ethical nuances. Perhaps all that can be said is that patients are more likely to be better served by offering all too much information than too little.

Appendix 1
More commentary on informed consent

Source: http://www-hsc.usc.edu/~mbernste/ethics.informed_consent.html (corrections added)

An article in the 1/9/00 NY Times Sunday magazine by Margaret Talbot on Placebos in Medicine also mentioned informed consent and made an interesting point: "Sometimes our contemporary notions of informed consent, important though they are, interfere with a doctor's capacity to offer hope and comfort. 'When, for example, a patient who is about to undergo a straight-forward surgical procedure anxiously asks the surgeon, 'Doctor, am I going to make it?' what should the surgeon say?' asks Walter Brown. 'Traditionally, the response would be to encourage the patient: 'You're in good hands here, everything will be fine.' Yet I have posed this scenario to a variety of physicians, both residents and attendings, and found that some consider themselves obligated to list the possible complications and risk of death, even if the morality rate from the procedure in miniscule.' Medical training that (rightly) values precise expression and a culture that values full disclosure and protection from liability may spur doctors to tell their patients the uninflected and deflating truths even in the most dire circumstances. But surely telling the whole truth and nothing but the truth is not the most humane or practical of counsel for doctors. Someone I know of, a physician herself, was recently operated on for a brain tumor. Her doctor chose his first postoperative visit in the hospital to tell her she would never work again. It didn't help her recovery much." This same NYT article made an interesting point about another, related topic- that of patients doing internet research and doing their own medical decision making in lieu of following a doctor's advice. It recounts the bout of Dr. Franz Ingelfinger, former editor of the New England Journal of Medicine, with esophageal cancer. He himself was a gastroenetrologist. He studied all relevant information from the literature and colleagues to make his own treatment decision. This resulted, he wrote, “in he and his family becoming increasingly confused and emotionally distraught. Finally when the pangs of indecision had become nearly intolerable, one wise physician friend said, 'What you need is a doctor.' He was telling me to forget the information I was receiving from many quarters, and to seek instead a person who would dominate, who would tell me what to do." When he found that person, Ingelfinger felt an "immediate and immense relief."

Multiple choice questions to accompany
Autonomy, Informed Consent and the Death of Therapeutic Privilege: Lessons Learned from the Jehovah’s Witnesses

[1] Which of the following is NOT one of the four guiding principles of the “Georgetown School” of bioethics

a)	autonomy

b)	compassion

c)	beneficence

d)	justice

[2] Which of the flowing standards of informed consent is most commonly employed in clinical care in Canada and the USA:|

a)	reasonable physician standard

b)	reasonable patient standard

c)	subjective standard

d)	objective standard

[3] In the case of the Jehovah’s Witness patient refusing a clinically necessary blood transfusion, the principle of beneficence comes into conflict with which of the following principles:

a)	autonomy

b)	compassion

c)	beneficence

d)	justice

[4] Obtaining informed consent entails ensuring that the patient:

a)	understands the various clinical choices available

b)	can discuss the issues with caregivers in a reasonable and logical manner

c)	is not being dictated to or controlled by other parties

d)	all of the above

[5] Which of the following concerning “therapeutic privilege” is FALSE

a)	It refers to the withholding of important information by the clinician in the belief that the information would lead to harm or suffering.

b)	The basis for therapeutic privilege is the notion that beneficence should take precedence over autonomy.

c)	The exercise of therapeutic privilege is becoming increasing common in modern clinical care.

d)	The exercise of therapeutic privilege is considered to be paternalistic

[6] Under which of the following circumstances can the acquisition of informed consent be problematic: a)	the heavily medicated patient

b)	the parturient in hard labor

c)	the patient with severe organic brain disease

d)	all of the above

[7] Some clinicians maintain that the process of informed consent has potential health risks in and of itself. Under which circumstance would this apply:

a)	in the case of a patient who is illiterate

b)	in the case of a patient who faces a language barrier

c)	in the case of a patient is who refuses a intervention involving a very small risk even though it would eliminate another, much larger, clinical risk.

d)	in all of the above cases

[8] Which of the following is an unacceptable option for patients who want very detailed risk information as part of the consent process

a)	answer every question asked in as much detail as possible

b)	refer patients to the peer-reviewed medical literature

c)	allow the patient access to the files of patients who have had similar procedures

d)	all of the above [9] Difficulties with using malpractice suit information as an indicator of clinical skill includes which of the following:

a)	more experienced clinicians have had more chance to get sued in their career

b)	the public may misinterpret malpractice history data and punish capable doctors who happen to treat a large number of high-risk patients

c)	friendly and compassionate doctors who are  incompetent are sued less frequently than other incompetent doctors

d)	all of the above [10] Which of the following intravenous products will orthodox Jehovah’s Witnesses accept?

a)	saline solution

b)	packed red blood cells

c)	plasma

d)	platelets and white blood cells

[11] The determination that blood transfusions were a violation of God's law in the Jehovah's Witnesses faith was made

a)	based on concerns about disease transmission

b)	based on biblical passages

c)	based on a distrust of the medical profession

d)	all of the above

[12] In Canada, the landmark legal case regarding the clinical care of Jehovah's Witness patients was the case of

a)	Malette v. North York Hospital

b)	Schloendorff v. North York Hospital

c)	Kramer v. Kramer

d)	Malette v. Shulman

title: Jehovah's Witness Informed Consent


text:
Radiation Oncology/Prostate/Salvage RT

 * See also: Natural history of PSA after RP in Prostatectomy
 * See also: Clinical and Pathologic Factors predicting recurrence in Adjuvant RT

PSA Failure post-Radical Prostatectomy

 * See PSA Failure

Probability of positive bone scan with rising PSA:
 * MSKCC, 2005 - PMID 15774789 — "Pattern of prostate-specific antigen (PSA) failure dictates the probability of a positive bone scan in patients with an increasing PSA after radical prostatectomy." Dotan ZA et al. J Clin Oncol. 2005 Mar 20;23(9):1962-8.
 * Article provides a handy nomogram.

Workup
Bone scan: not recommended. Chance of positive bone scan is <5% until PSA reaches 30-40. (PMID 9751361)

Prostate re-biopsy is not necessary and The PSA level or threshold seemed to be 1.5 ng/mL.
 * ASTRO consensus panel - PMID 10561174 — "Consensus statements on radiation therapy of prostate cancer: guidelines for prostate re-biopsy after radiation and for radiation therapy with rising prostate-specific antigen levels after radical prostatectomy. American Society for Therapeutic Radiology and Oncology Consensus Panel." Cox et al. J Clin Oncol 1999 17:1155-1163.
 * The panel judged that prostate re-biopsy is not necessary as standard follow-up care and that the absence of a rising PSA level after radiation therapy is the most rigorous end point of total tumor eradication.
 * The panel noted that most data indicate the PSA level at time of salvage radiation may make a prognostic difference in outcome. The PSA level or threshold, based on the data presented, seemed to be 1.5 ng/mL.
 * Based on the data presented at this conference, the dose should be 64 Gy or slightly higher with standard fractionation (1.8 or 2.0 Gy per fraction).
 * There is no standard role for androgen suppression therapy in patients with or without radiation therapy for rising PSA values after prostatectomy.

ProstaScint: (indium 111-capromab pendetide)
 * ProstaScint study group (1987-95)
 * PMID 11920467, 2002 — "Clinical utility of indium 111-capromab pendetide immunoscintigraphy in the detection of early, recurrent prostate carcinoma after radical prostatectomy." Raj GV et al. Cancer. 2002 Feb 15;94(4):987-96.
 * 255 pts with rising PSA (but < 4 ng/mL) after prostatectomy, who had negative bone scans and negative nodes, underwent ProstaScint scan.
 * Uptake in 72%; 31% in prostatic fossa only. Avg PSA 1.1 (all pts). Serum PSA did not correlate with pattern of positive scan.

Outcome
Predictors of progression after salvage RT include Gleason Score 8-10, pre-RT PSA >2, negative surgical margins, PSA-DT <10 months and seminal vesicle invasion.

 * Duke/Harvard; 2011 (1988-2008) PMID 21437885 -- "Salvage radiation in men after prostate-specific antigen failure and the risk of death." (Cotter SE, Cancer. 2011 Mar 22. doi: 10.1002/cncr.25993. [Epub ahead of print])
 * Retrospective. 519 men treated with RP at Duke, with PSA failure. Median F/U 11.3 years
 * Outcome: Salvage RT reduction in all-cause mortality (HR 0.5, SS)
 * Conclusion: Salvage RT is associated with a decreased risk in mortality
 * Johns Hopkins; 2008 (1982-2004) PMID 18560003 -- "Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy." (Trock BJ, JAMA. 2008 Jun 18;299(23):2760-9.)
 * Retrospective. Compared cohorts of pts who had biochemical failure after RP (n=635) from those who had 1) no salvage treatment (397 pts), 2) salvage RT alone (160), or 3) salvage RT + hormones (78).
 * Median f/u 6 yrs after recurrence. Death from prostate cancer in 18% (116 pts). Risk of death with observation, 22% (89 deaths); following salvage RT, 11% (18 deaths); following RT + hormones, 12% (9 deaths). Salvage RT with 3-fold increase in PC-specific survival (HR=0.32) and OS. Addition of hormonal therapy not associated with additional increase in survival.
 * Increase in survival with RT was limited to pts with PSA doubling time < 6 months. Salvage RT after 2 yrs provided no survival advantage. Men who did not achieve bNED after salvage RT did not experience an increase in survival.

 * Multi-institutional
 * 2004 PMID 15026399 -- Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy. (2004 Stephenson AJ, JAMA)
 * Retrospective review of 501 patients at 5 US academic tertiary centers who received salvage RT; median follow-up 45 months
 * 4-year PFS was 45%
 * No risk factors 4-year PFP was 77%
 * Multivariate predictors of progression:
 * Gleason Score 8-10 (HR 2.6)
 * Pre-RT post-relapse PSA >2.0 (HR 2.3)
 * Negative surgical margins (HR 1.9)
 * PSA-DT <10 months (HR 1.7)
 * Seminal vesicle invasion (HR 1.4)
 * Conclusion : "The Authors conducted a multicenter analysis of 501 patients undergoing salvage radiotherapy for an increasing PSA level after radical prostatectomy in order to reliably identify prognostic variables associated with a durable response.
 * In this cohort, a Gleason score of 8 to 10, preradiotherapy PSA level greater than 2.0 ng/mL, negative surgical margins, PSADT of 10 months or less, and seminal vesicle invasion were significant predictors of disease progression despite salvage radiotherapy.
 * In their multivariable analysis, only preradiotherapy PSA level greater than 2.0 ng/mL had a significant association with progression after salvage radiotherapy. However, patients receiving treatment at very low PSA levels (<0.6 ng/mL) had an improved outcome compared with patients with a preradiotherapy PSA level between 0.61 and 2.0 ng/mL. But the use of very low PSA thresholds risks overtreating patients whose PSA level is detectable due to residual benign prostatic tissue.
 * A patient with positive margins who relapses is more likely to benefit from salvage radiotherapy than a patient with negative margins, whose PSA level is more likely to represent distant disease.
 * patients with Gleason scores of 4 to 7 and a rapid PSADT, 67% will have a durable response to early salvage radiotherapy if they have positive surgical margins,
 * compared with 22% for those having negative margins.
 * Patients with a Gleason score of 4 to 7 and a slow PSADT (>10 months) had a 4-year PFP greater than 70% when radiation was delivered early, when the PSA level was lower.
 * Gives flowchart to predict progression-free probability after salvage RT based on Gleason score, Pre-RT PSA, Surgical margins, and PSADT.
 * 2007 Update PMID 17513807 -- "Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy." (Stephenson AJ, J Clin Oncol. 2007 May 20;25(15):2035-41.)
 * Updates previous report with larger cohort and longer follow up; 1540 pts from 17 centers, median f/u 53 months.
 * Median pre-RT PSA 1.1, median doubling time 6.9 months. Median 64.8 Gy.
 * 6-yr PFP 32%. By pre-RT PSA: 6-yr PFP 48% for PSA <0.50, 40% 0.51-1.00, 28% 1.01-1.5, 18% >1.5.
 * PSA response: nadir of ≤0.10 achieved in 59% following RT
 * Nomogram and flowchart to predict PFP.
 * 2016: New Contemporary Update PMID 27528718 -- "Contemporary Update of a Multi-Institutional Predictive Nomogram for Salvage Radiotherapy After Radical Prostatectomy." (Tendulkar RD, J Clin Oncol. 2016 Aug 15. [Epub ahead of print])
 * New cohort, including 2460 pts from 10 centers. Median f/u 5 yrs. Median pre-SRT PSA 0.5
 * Includes pts with lower pre-SRT PSA values <= 0.20 (18% of pts) who were excluded from the previous cohorts.
 * On multivariable analysis, pre-SRT PSA, GS, EPE, SVI, surgical margins, ADT use, and SRT dose were associated with FFBF. Pre-SRT PSA, GS, SVI, surgical margins, and ADT use were associated with DM, whereas EPE and SRT dose were not.
 * Conclusion: "Early SRT at low PSA levels after RP is associated with improved FFBF and DM rates. Contemporary nomograms can estimate individual patient outcomes after SRT in the modern era."

 * PMID 7513108 - "Evaluation of serum prostate-specific antigen velocity after radical prostatectomy to distinguish local recurrence from distant metastases." Partin et al. Urology. 1994 May;43(5):649-59.
 * Proposed criteria to distinguish local recurrence from distant metastases for patients with an increasing PSA level after radical prostatectomy. A Gleason score of 8 to 10, seminal vesicle invasion, positive lymph nodes, and a rapid PSA velocity were associated with distant metastases. Local recurrence was more frequently observed in patients with low-grade and organ-confined disease, a slow PSA velocity, and a disease free interval greater than 3 years, suggesting that isolated local recurrence has a low metastatic potential.

 * Virginia Commonwealth University and University of Florida - PMID 15145145 — Comparison Of Adjuvant Versus Salvage Radiotherapy Policies For Postprostatectomy Radiotherapy. Hagan et al. Int. J. Radiation Oncology Biol. Phys., Vol. 59, No. 2, pp. 329–340, 2004
 * The Authors compared the long-term results of postprostatectomy radiotherapy (RT) from two institutions, one adapting a prospective policy of adjuvant RT (69 patients) and the other salvage RT (88 patients). The salvage group underwent RT after longer postoperative intervals (median, 40.3 vs. 2.9 months; p <0.0001) and had higher prostate-specific antigen (PSA) values before starting RT (4.5 vs. 0.86 ng/mL; p = 0.003). Both groups were routinely treated to a minimal total dose of 60 Gy.
 * Results: Of the 69 patients referred for adjuvant RT, 22 (32%) had nonzero PSA values before RT. Multivariable modeling of BRFS found only the PSA value before RT to be statistically significant (p <0.0001). RT after prostatectomy was equally effective in either setting when the pre-RT PSA level was <1 ng/mL. When the PSA value before RT was >1 ng/mL, the 5-year BRFS for each group was inferior.
 * Conclusion : Durable biochemical control is re-established in approximately 50% of patients who undergo salvage treatment, and 70–80% of patients in adjuvant series have disease control. Although the adjuvant treatment policy was associated with significantly improved BRFS, this was attributable to low pre-RT PSA values. When the treatment groups were stratified for pre-RT PSA level, the differences in BRFS were not statistically significant. Patients with a rising PSA level after prostatectomy, regardless of their initial risk, should receive prompt referral for RT.

 * University of Heidelberg (Germany), 2007 (1991-2004)
 * PMID 17275204 — "Long-term results and predictive factors of three-dimensional conformal salvage radiotherapy for biochemical relapse after prostatectomy." Neuhof D et al. Int J Radiat Oncol Biol Phys. 2007 Jan 31. [Epub ahead of print]
 * 171 pts. Median f/u 39 mos.
 * PSA decreased after RT in 82.5%. 5-yr bRFS 35.1%. On multivar. analysis, only Gleason score and pre-RT PSA level were predictive of PSA recurrence.

 * Mayo, 2000 (1987-96)
 * PMID 10687990 — "Radiotherapy for isolated serum prostate specific antigen elevation after prostatectomy for prostate cancer." Pisansky TM et al. J Urol. 2000 Mar;163(3):845-50.
 * 166 pts. Median f/u 52 mos.
 * 5-yr bRFS 46%. Predictors for relapse: SV invasion, tumor grade, pre-RT PSA.

Use of ProstaScint imaging:
 * University of Chicago, 2008 (1988-2005)
 * PMID 18234446 — "Salvage radiotherapy after postprostatectomy biochemical failure: does pretreatment radioimmunoscintigraphy help select patients with locally confined disease?" (Liawu SL, Int J Radiat Oncol Biol Phys. 2008 Aug 1;71(5):1316-21.)
 * Retrospective, 82 pts. Compared outcomes for patients undergoing salvage RT with or without the use of pre-RT ProstaScint (RIS) scans. All pts had persistently elevated or increasing post-op PSA >0.1. Median pre-RT PSA 0.637. 3% had negative CT scan and/or bone scan. 47 pts had pre-RT ProstaScint scan. Pts were not included on the study if they had a RIS scan showing distant disease. RT was to median dose 66 Gy and included prostate bed (91% with RIS, 83% without) or pelvis + prostate bed (6% and 17%).
 * Patients who had prostate bed-only uptake on RIS did not have improved outcomes, with biochemical control of 40% at 5 years. Positive margins were associated with improved control.
 * Patients

RT + Hormonal Therapy
Preliminary Trials:
 * RTOG 96-01 (1998-2003) -- Post-op RT +/- Casodex 150 mg x 2 years for pT3 with PSA elevation.
 * pT3N0 (or pT2N0 with positive surgical margin) with post-op PSA 0.2-4.0. Randomized to prostate bed RT 64.8 Gy +/- casodex beginning concurrent with RT.
 * ASTRO 2010 Report with 7.1 years of follow up:
 * Freedom from PSA progression at 7 yrs: 57% vs. 40% (p<0.01)
 * True across all Gleason scores
 * Cumulative incidence of metastatic disease at 7 years: 7.4% vs. 12.6% (p<0.04)
 * Not reporting survival yet given too few events
 * Grade 3/4 Toxicity:
 * GI: 2.3% vs. 1.4%
 * Bladder: 5.9% vs 5.0%
 * Gynecomastia (predominantly grades 1/2): 89% vs. 15%

Radiation Volume
Whole Pelvis vs Prostate Bed Only:
 * Stanford, 2007 (1985-2005) PMID 17459606 -- "Radiotherapy after prostatectomy: improved biochemical relapse-free survival with whole pelvic compared with prostate bed only for high-risk patients." (Spiotto MT, Int J Radiat Oncol Biol Phys. 2007 Sep 1;69(1):54-61.)
 * Retrospective. 160 pts, treated with adjuvant (21 pts) or salvage RT (139). Androgen suppression in 87. 114 pts considered 'high risk' for LN+ based on: GS >= 8, PSA > 20, SV+, prostate capsule involvement, or pN+. Of the high risk group, 72 treated with WPRT and 42 with RT to prostate bed only.
 * Benefit of WPRT limited to high risk pts: 5-yr BRFS 47% (WPRT) vs 21% (PO). Benefit for androgen suppression when given concurrently with RT.
 * Conclusion: WPRT confers superior bRFS compared with PBRT for high-risk patients receiving adjuvant or salvage RT after radical prostatectomy. This advantage was observed only with concurrent TAS.

Timing of Salvage RT
Systematic Reviews:
 * 2012: UCLA PMID 22795730 -- "The timing of salvage radiotherapy after radical prostatectomy: a systematic review." (King CR, Int J Radiat Oncol Biol Phys. 2012 Sep 1;84(1):104-11.)
 * Review of 41 studies (published 1995-2012) including 5597 patients.
 * PSA level before SRT and RT dose associated with RFS. Average 2.6% loss of RFS for each incremental 0.1 PSA at the time of SRT.
 * Conclusion: "This study provides Level 2a evidence for initiating SRT at the lowest possible PSA. Dose escalation is also suggested by the data."

High Dose Salvage RT
high dose in this context refers to a dose >= 66 Gy

 * 2012: MSKCC (1988-2007) PMID 22300563 -- "Long-term outcomes after high-dose postprostatectomy salvage radiation treatment." (Goenka A, Int J Radiat Oncol Biol Phys. 2012 Sep 1;84(1):112-8.)
 * 285 pts treated with salvage RT. Median PSA before SRT 0.4. 60 pts (21%) had MRI-detected local recurrence. 42 pts had pathologic confirmation of local recurrence.
 * 95% were treated to a dose >= 66 Gy; 72% received >= 70 Gy. ADT used in 31%.
 * Median f/u 60 mo. 7-yr bRFS 37%, DMFS 77%. Predictors of recurrence: vascular invasion, negative margins, presalvage PSA > 0.4, no use of ADT, Gleason >= 7, and +SV. RT dose >= 70 Gy was not associated with improved biochemical control. PSA-DT < 3 months was the only indep. predictor of DM. Trend toward benefit of dose >= 70 Gy in decreasing clinical local failure in pts who had radiographically visible local disease at the time of SRT.
 * Conclusion: "Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in patients with greater burden of disease at time of SRT as reflected by either radiographic imaging or a greater PSA level. Salvage radiation doses ≥70 Gy may ultimately be most beneficial in these patients, but this needs to be further studied."

PSA measurements during RT

 * PMID 12240547 — "The value of PSA measurements at 30 Gy, 50 Gy and 60 Gy for dose limitation in patients with radiotherapy for PSA increase after radical prostatectomy." Wiegel T et al. Strahlenther Onkol. 2002 Aug;178(8):422-5.
 * 41 pts treated to 66.6 Gy. At 30 Gy, 26% of those who would eventually respond still had a rising PSA, but at 50 and 60 Gy, 93% had decreasing PSA. In those who would fail, 75% and 88% had rising PSA at 50 and 60 Gy.

 * PMID 11483332 — "Serum PSA evaluations during salvage radiotherapy for post-prostatectomy biochemical failures as prognosticators for treatment outcomes." Do T et al.  Int J Radiat Oncol Biol Phys. 2001 Aug 1;50(5):1220-5.
 * 41 patients with biochemical failure after RP had PSA were treated to 59.4-66.6 Gy without hormone therapy. PSA checked at 30 Gy and 45 Gy.
 * Rising PSA at 45 Gy significantly predicted for poor outcome. PSA at 30 Gy did not significantly predict for disease outcome.

Toxicity

 * Mayo, 2009 (1987-2003) PMID 19766337 -- "Late toxicity after postprostatectomy salvage radiation therapy." (Peterson JL, Radiother Oncol. 2009 Nov;93(2):203-6.)
 * Retrospective. 308 pts treated at Mayo-Rochester or Mayo-Jacksonville. Median RT dose 64.8 Gy; no IMRT. Hormonal therapy in 19%.
 * Late complication (any grade) in 14% by 5 yrs. Grade 3-4 complication: 4 pts (0.7%). GU toxicity: 3.9% gr 2 urethral strictures, 3 pts with gr 3 cystitis. GI: 1 pt with gr 4 rectal complication.

Radiation Injury

 * Toronto Sunnybrook PMID 15936551 -- Effect of androgen suppression on hemoglobin in prostate cancer patients undergoing salvage radiotherapy plus 2-year buserelin acetate for rising PSA after surgery. ( 2005 Chander S, Int J Radiat Oncol Biol Phys.)
 * Conclusion : "Two-year AS resulted in a statistically significant drop in the mean Hb, but had no clinically apparent adverse effect. The pattern of Hb change was similar to that of testosterone change."

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Radiation Oncology/Prostate/Salvage RT


text:
User talk:68.35.254.46

Please don't experiment with wikibooks. If you feel the need to be destructive, go elsewhere. If you persist in vandalous acts, you will be blocked from editing. Firefox 22:19, 21 Jun 2005 (UTC)

title: User talk:68.35.254.46


text:
User:Ilg

(n.b. my comprehension of Spanish and Interlingua are much better than my construction.)

 * Graduate of University of Chicago and New York University
 * Mathematics Faculty at Illinois Mathematics and Science Academy
 * Head Coach, Chicago ARML teams
 * North Suburban Mathematics League Board Member, Oral Topics Chair, and Contingency Rules Chair
 * ICTM Contest Committee Member and Oral Competition Judge

title: User:Ilg


text:
Talk:Traditional Chinese Medicine

I look forward to more of your new article on traditional Chinese medicine. But, the page name is a bit confusing. TCM could also mean Turner Classic Movies, Trinity College of Music, or Toolkit for Conceptual Modeling. It's normal to spell it out in full. In this case, maybe you could rename the page to Traditional Chinese medicine project or more simply Traditional Chinese medicine. To do it you simply click on the move tab when looking at your page. (Donovan|Geocachernemesis|Interact) 00:29, 22 Jun 2005 (UTC)
 * ✅ along with subpages. — Mike.lifeguard | talk 20:06, 17 January 2009 (UTC)

title: Talk:Traditional Chinese Medicine


text:
Ada Programming/Attributes/'Val

Description
The 'Val attribute is defined for all discrete types. It is a function returning that value of the base type of S having the argument's position number; the prefix S must be a subtype name. (Any specific integer type is implicitly converted to universal_integer.)

S'Val (Arg: universal_integer) S'Base;

If no value of the type of S has the position number Arg, the Constraint_Error exception is raised.

Note that representation clauses do not affect position numbering. Whatever underlying value the enumerated value has, the position number will remain the same.

Example
My_Enum (Enum1, Enum2, Enum3); My_Other_Enum (Value1, Value2, Value3); My_Other_Enum (Value1 => 2, Value2 => 4, Value3 => 6); (My_Enum'Val(0) = Enum1); (My_Enum'Val(1) = Enum2); (My_Enum'Val(2) = Enum3); (My_Other_Enum'Val(0) = Value1); (My_Other_Enum'Val(1) = Value2); (My_Other_Enum'Val(2) = Value3); (My_Enum'Val(3)      = Enum3); (My_Other_Enum'Val(2) = Value1); (My_Other_Enum'Val(4) = Value2); (My_Other_Enum'Val(6) = Value3);

Other example:

Color (RED, BLUE, WHITE); OBJECT : Color := WHITE; Put (Color'Val (1));

The internal representation can only be queried via Unchecked_Conversion.

Wikibook

 * Ada Programming
 * Ada Programming/Attributes
 * Ada Programming/Attributes/'Pos

Ada Reference Manual

|Val

title: Ada Programming/Attributes/'Val


text:
Ada Programming/Attributes/'First

Description
, where  is any scalar subtype (for example integer, enumerated, real), is an attribute that represents the first value (lower bound) in the range of.

, where  is an array, denotes the first index value. For more-dimensional arrays,  denotes the first index value of the Nth dimension (N must be static).

Example
My_Enum (Enum1, Enum2, Enum3); My_Int   -1 .. 5; ...  (My_Enum'First = Enum1); (My_Int'First = -1); (My_Int'First =  0);

Wikibook

 * Ada Programming
 * Ada Programming/Attributes

Ada Reference Manual

|First

title: Ada Programming/Attributes/'First


text:
JavaScript/DHTML

DHTML - an abbreviation for Dynamic HTML - is a term denoting the combination of HTML, JavaScript, and CSS. It does not introduce or define any new technology.

This page offers some examples of integrating HTML, JavaScript, and CSS.

messages
This will give a simple alert message.

This will give a simple prompt message.

This will give a simple confirmation message.

Button and alert
Sometimes it is best to dig straight in with the coding. Here is an example of a small piece of code:

What does this code do? When it loads, it tells what value the variable  should have. The following code snippet is a function that has been named "bomb". The body of this function fires some alert messages and changes the value of.

The next part is mainly HTML, with a bit of JavaScript attached to the INPUT tags. The "onclick" property tells its parent what has to be done when clicked. The  function is assigned to the first button; the second button just shows an alert message with the value of.

Two scripts
Now, back to the first example. We have modified the script, adding a different welcome message. This version requests the user to enter a name. They are also asked if they want to visit the site. Some CSS has also been added to the button.

title: JavaScript/DHTML


text:
User talk:O'boise

Hello and welcome to Wikibooks!

Here are some tips to help you get started:

 * It's best if you don't sign your work in articles, instead, save it for talk pages.
 * Check out our help page if you need additional help.
 * Eventually, you might want to read the Manual of Style and Policies and Guidelines.
 * Remember to maintain a Neutral point of view.
 * Explore, be bold in editing pages, and have fun!

Good luck!

(Donovan|Geocachernemesis|Interact) 02:46, 22 Jun 2005 (UTC)

title: User talk:O'boise


text:
JavaScript/Handling DOM events

Applications with a user interface - and other application types - are predominantly driven by events. Here we focus on DOM events. They originate (or fire) from specific actions or situations in a browser or a native app, e.g., a user clicks with the mouse, types a keyboard key, or works on a touch screen; a visual object is 'dragged & dropped', 'copied & pasted', or resized; the HTML page is loaded or shall be unloaded; the browser or a visual object gets or loses the focus; and much more. It's also possible that the application creates events programmatically (dispatch).

An event is related to its originating object and with a JavaScript statement; that is, in most cases, a call to a function that is denoted as the event handler. The JavaScript part is invoked after the event arises. Common actions are communication with a server, validation of user input, or modification of DOM or graphics.

Embedded in HTML
A short example shows how events are defined in an HTML page, fire, and execute. This syntax version is denoted as inline JavaScript.

When a user clicks on one of the buttons, the browser reads the button's attribute, creates a JavaScript object that contains all properties of the event, and executes the JavaScript statement(s). Mostly, the JavaScript part is a call to a function. That function is denoted the event handler. It receives the JavaScript object as its first parameter. Only in very simple cases, the complete JavaScript script is inlined.

Of course, the called function must exist somewhere. Some standard functions like  are predefined and provided by the browser. Your self-written functions exist within the HTML tag, or the tag refers to a file or URL where they exist.

Hint: Embedding event definitions directly into HTML is called inline JavaScript. It's the earliest method of registering event handlers, but it tends to make the source hard to read for non-trivial applications. Therefore it can be seen as being a less desirable technique than other unobtrusive techniques; see next chapter. The use of inline JavaScript can be considered to be similar in nature to that of using inline CSS, where HTML is styled by putting CSS in  attributes.

Nevertheless, the Wikibook on hand will use inline JavaScript often in its demonstration pages because the syntax is short and the concept is easy to understand.

Programmatically in JavaScript
JavaScript knows two ways to register an event handler for an HTML element. First, the event handler function can be directly assigned to the element's properties  (onclick, onkeydown, onload, onfocus, ...). Their name starts with 'on' and ends with the value of the event type. Second, the function  registers the event type and the event handler.

The onclick event handler 'register' of button 'button_1' is registered with the above inline JavaScript syntax. When the page loads, only this event handler is known. Clicks to the paragraph 'p1' don't trigger any action because it does not have any event handler so far. But when the button gets pressed, the handler of button 'button_1' registers the second event handler, the function 'showMessage'. Now, after a click on the paragraph, the alert "A click-event to the paragraph..." occurs.

The registration is done in line 10. The noticeable difference to the inline JavaScript is that there are no parenthesizes. The inline JavaScript calls the function  and hence needs to use parenthesizes. The function  does NOT call. It uses only its name for the registration process.

The alternative to assigning the function to the paragraph's 'onclick' property is the use of the function. It acts on the element 'p1' and takes two parameters. The first one is the event type (click, keydown, ...). Such event types correlate with the onxxx names in that they miss the first two characters 'on'. The second parameter is the name of the function that acts as the event handler.

You can test the example by commenting out either line 10 or line 12. Line 12 with the  function is the preferred version.

Event types
Different kinds of events exist depending on the kind of the originating element. The complete list of event types is incredibly huge (MDN) (W3schools). We show some important types and examples.

The following example demonstrates some different event types.

When the page is loaded, the onload event of the  is fired. Please notice that here the 'on' prefix is necessary because it's the inline JavaScript syntax (line 23). The called function registerAllEvents locates diverse HTML elements and registers event handlers of different types (lines 8 - 13). Often you will register different functions, but to keep things easy, we register in this example the same function handleAllEvents to all elements. This function reports the event type and the originating HTML element.

Event properties
The event is always passed to the event handler as its first parameter in the form of a JavaScript object. JavaScript objects consist of properties; properties are key/value pairs. In all cases, one of the keys is 'type'. It contains the event's type; some of its possible values are shown in the above table. Depending on the event type, a lot of other properties are available.

Here are some examples of more or less important properties.

An example of accessing a property is given in the following script.

A mouse-move event is registered for the. Whenever the mouse moves across the body, the event is triggered. The event handler reads the x/y properties out of the JavaScript object and shows them in the title of the browser's active tab.

removeEventListener
Similar to  the function   removes an event listener from an element.

Synthetic events
The system offers the above-shown rich set of event types. Additionally, you can create your own events and trigger them from your application.

First, you create a function with one parameter, the event handler. Next, you register this event handler for an element. So far, everything is the same as with predefined event types.

Now you can trigger this event in any part of your application. To do so, you create a new event of precisely the chosen type and fire it with a call to.

For test purposes, we bind this functionality to the button. The complete page now looks like this:

At the beginning, the button listens to click events, and 'p1' listens to events of type 'click' as well as of type 'syntheticEvent'. When the button is clicked, his event handler 'triggerEvent' creates a new event of type 'syntheticEvent' and fires it on 'p1' (what is the primary purpose of this example). The event handler  shows a message without 'p1' being clicked. In other words: The event on 'p1' occurs without a click on 'p1'.

Possibly you need in the event handler some data from the calling function, e.g., the text of an error-message, the data of an HTTP response, ... . You can pass such data by using the  and its property 'detail':

Access the data in the event handle:

(A)synchronous behaviour
Most events are handled synchronously, e.g., 'click', 'key', or 'mouse'. But there are a few exceptions that are handled asynchronously, e.g., 'load'. 'Synchronous' means that the sequence of invocations is the same as the sequence of their creations. Clicking on Button A, B, and then C leads to the invocation of A's, B's, and then C's event handler in exactly this sequence. In contrast, 'asynchronous' events can lead to the invocation of the correlated handlers in an arbitrary sequence.

You must distinguish this question, the invocation of event handlers, from the implementation of their bodies. Every implementation may act strictly sequential or may contain asynchronous calls - it depends on your intention. Typical asynchronous calls are HTTP requests or database queries. Of course, they can be part of the handler of a click event.

Exercises

 * ... are available on another page (click here).

title: JavaScript/Handling DOM events


text:
Radiation Oncology/Small intestine

Epidemiology
Account for only 2% of malignant tumors of the GI tract in spite of the small bowel accounting for 75% of the length and 90% of the surface area of the gut.

5,000 cases/year. 1,200 deaths.

Presentation
Small bowel neoplasms generally present with pain, obstruction, bleeding, anorexia, weight loss and sometimes jaundice. Small bowel neoplasms are more common in the proximal small bowel (duodenum > jejunum > ileum). Most occur in the 1st or 2nd portion of the duodenum. Adenocarcinomas of the duodenum tend to lead to small bowel obstruction.

Anatomy
Duodenum is 25 cm in length. Jejunum is 8 ft in length. Ileum is 12 ft in length. There is no abrupt division between the jejunum and ileum. The duodenum is retroperitoneal, whereas the remainder of the bowel is encased in mesentery. The duodenum is divided into four portions. The first portion of the duodenum is defined as the portion sitting underneath the gall bladder and quadrate lobe of the liver. The second portion of the duodenum is the concave portion. The third portion of the duodenum is portion that lies horizontally at the level of the 3rd lumbar vertebral body. The fourth portion of the duodenum ascends to the 2nd lumbar vertebral body.

Lymphatics
Lymph nodes are located along the mesenteric vessels to the root of the mesentery.

Regional nodes include: For duodenum: duodenal, hepatic, pancreaticoduodenal, infrapyloric, gastroduodenal, pyloric, superior mesenteric, pericholedochal For ileum and jejunum: posterior cecal, ileocolic, superior mesenteric, mesenteric NOS

Distant mets: celiac axis

Pathology
45% of small bowel malignancies are adenocarcinomas. Other histologies include carcinoid, lymphoma, sarcoma and GIST. Carcinoid is the most common histology of the distal small bowel.

Staging
Does not include lymphomas, carcinoid tumors, or GISTs. Does not include tumors arising from the ileocecal valve or from Meckel's diverticula. Tumors from the ampulla of vater have their own staging system.

AJCC 7th Edition (2009) Is similar to that for colon/rectum but has only N1 and no subdivisions of overall stage

Tumor Nodes
 * T1a - invades lamina propria
 * T1b - invades submucosa
 * T2 - invades muscularis propria
 * T3 - invades through muscularis propria into the subserosa or into the nonperitonealized perimuscular tissue (mesentery or retroperitoneum) with extension 2 cm or less
 * T4 - perforates the visceral peritoneum or directly invades other organs or structures (includes other loops of small bowel, mesentery, or retroperitoneum more than 2 cm, and abdominal wall by way of serosa; for duodenum only, invasion of pancreas or bile duct)
 * N0 - no regional lymph node metastasis
 * N1 - metastasis in 1-3 lymph nodes
 * N2 - metastasis in 4 or more lymph nodes
 * regional nodes: celiac nodes are considered M1. Regional nodes include: (duodenum) - duodenal, hepatic, pancreaticoduodenal, infrapyloric, gastroduodenal, pyloric, superior mesenteric, pericholedochal; (ileum and jejunum) - cecal, ileocolic, superior mesenteric, mesenteric

Metastasis Stage grouping Changes from 6th edition:
 * M0 - no
 * M1 - yes
 * I - T1-T2 N0
 * IIA - T3 N0 M0
 * IIB - T4 N0 M0
 * IIIA - N1
 * IIIB - N2
 * IV - M1
 * Subdivided T1 into T1a/b
 * T3 and T4 are similar but modified slightly
 * N category changed from N0-1 to N0-2
 * Stage II subdivided into IIA and IIB, Stage III subdivided into IIIA and IIIB

Older staging systems
AJCC 6th Edition (2002)

 * T1 - invades lamina propria or submucosa
 * T2 - invades muscularis propria
 * T3 - invades into subserosa or into non-peritonealized pericoloic or perirectal tissues
 * T4 - invades other organs or structures or perforates visceral peritoneum

 * N1 - regional lymph node metastases

Stage grouping:
 * I - T1-2 N0 M0
 * II - T3-4 N0 M0
 * III - N1
 * IV - M1

Changes in AJCC staging:
 * No changes from the 5th edition

Treatment
Treatment depends on the portion of the small bowel affected. Adenocarcinomas of the 2nd or 3rd portion of the duodenum are treated with pylorus-sparing pancreaticoduodenectomy. Adenocarcinomas of other regions of the small bowel may be treated with segmental resection plus regional lymphadenectomy.

The role for adjuvant chemotherapy remains undefined, but 5FU is considered to be the agent of choice.

Indications for adjuvant radiation may include close or positive margins. Adjuvant radiation is generally given concurrently with chemotherapy.

Duodenum
 * Duke; 2007 (1975-2005) PMID 17689032 -- "Duodenal adenocarcinoma: patterns of failure after resection and the role of chemoradiotherapy." (Kelsey CR, Int J Radiat Oncol Biol Phys. 2007 Dec 1;69(5):1436-41. Epub 2007 Aug 6.)
 * Retrospective. 32 patients. Surgery alone (n=16), neoadjuvant chemo-RT (n=11), adjuvant chemo-RT (n=5). Median RT dose 50.4 Gy, concurrent 5-FU based chemo.
 * Outcome: 5-year OS 48%, DFS 47%, LC 55%. No difference if surgery alone or surgery with chemo-RT
 * Conclusion: Local failure after surgery high, chemo-RT should be considered

title: Radiation Oncology/Small intestine


text:
User talk:Goldweard~enwikibooks

Hello and welcome to Wikibooks!

I'm sorry I didn't welcome you earlier.

Here are some tips to help you get started:

 * Remember to conduct all of your editing experiments in the sandbox.
 * Check out our help page if you need additional help.
 * Eventually, you might want to read the Manual of Style and Policies and Guidelines.
 * Remember to maintain a Neutral point of view.
 * Explore, be bold in editing pages, and have fun!

Good luck!

(Donovan|Geocachernemesis|Interact) 04:54, 22 Jun 2005 (UTC)

Your account will be renamed
Hello,

The developer team at Wikimedia is making some changes to how accounts work, as part of our on-going efforts to provide new and better tools for our users like cross-wiki notifications. These changes will mean you have the same account name everywhere. This will let us give you new features that will help you edit and discuss better, and allow more flexible user permissions for tools. One of the side-effects of this is that user accounts will now have to be unique across all 900 Wikimedia wikis. See the announcement for more information.

Unfortunately, your account clashes with another account also called Goldweard. To make sure that both of you can use all Wikimedia projects in future, we have reserved the name Goldweard~enwikibooks that only you will have. If you like it, you don't have to do anything. If you do not like it, you can pick out a different name.

Your account will still work as before, and you will be credited for all your edits made so far, but you will have to use the new account name when you log in.

Sorry for the inconvenience.

Yours, Keegan Peterzell Community Liaison, Wikimedia Foundation 23:11, 17 March 2015 (UTC)

Renamed
 This account has been renamed as part of single-user login finalisation. If you own this account you can |log in using your previous username and password for more information. If you do not like this account's new name, you can choose your own using this form after logging in: . -- Keegan (WMF) (talk) 05:00, 19 April 2015 (UTC)

title: User talk:Goldweard~enwikibooks


text:
Talk:Calculus/Differentiation

Implicit differnetiation, Derivatives of Hyperbolic and inverse hyperbolic Functions? Anyone?

- David

 * Good ideas. We do need them. Grimm
 * Made a stub page for Derivatives of Hyperbolic and inverse hyperbolic Functions, but we need more contributors. Musical Inquisit (discuss • contribs) 22:25, 9 December 2022 (UTC)

Organization
It seems many of these topics contain the same information (e.g. Basic Derivative Applications and Applications of Derivatives). Could we possibly combine the information into one wikibook, and then split off if it grows too large, as opposed to having several smaller books which contain the same information or are needed together to fully understand them?--SimRPGman 21:52, 11 November 2005 (UTC)

 * Hi. Do you have links to the two pages you mention? Are they separate books or modules in this book?  Do they currently have any useful content? Juliusross 02:21, 12 November 2005 (UTC)

Thoughts
I've spent some time going through the material in this section, but I'm out of time to make further improvements--at least for now. I think overall it's not too bad. Some of the applied topics are currently underdeveloped.

I've tried to add some proofs of the important theorems. One difficulty I encountered was the lack of formal development throughout the book that would put some of the more difficult proofs out of the reach of a reader whose only background is the book's prerequisites and the book's material up to that point. I think a less rigorous treatment is probably best for a book of this nature since a rigorous treatment would probably require a more tightly coupled collaborative effort. Nevertheless, I think the level of rigor could stand to be raised from its current level, but that would require lots of time and effort starting from the very beginning of the book.

An easier yet significant improvement could be made by adding more exercises (or improving the quality of the current exercises), especially exercises after some new concept has been introduced. I've tried to move away from having all the exercises at the very end, so I've added solution sub-pages for many of the pages to encourage the addition of new exercises on those pages.

I'm by no means an expert on the subject. In fact, I'm going through this book now because I'm very rusty, and I'm trying to re-learn the material. I've tried to double-check the answers I've added using wxmaxima, but it's very possible some of the answers I've given are wrong. The same goes for the proofs I've added. --Greenbreen (discuss • contribs) 08:22, 24 May 2011 (UTC)

title: Talk:Calculus/Differentiation


text:
User talk:203.217.22.2

Please don't experiment with wikibooks. If you feel the need to be destructive, go elsewhere. If you persist in vandalous acts, you will be blocked from editing. Firefox 05:48, 22 Jun 2005 (UTC)

title: User talk:203.217.22.2


text: User:Adeezoja

title: User:Adeezoja


text:
User talk:Adeezoja

Hello and welcome to Wikibooks!

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(Donovan|Geocachernemesis|Interact) 06:26, 22 Jun 2005 (UTC)

title: User talk:Adeezoja


text:
Talk:Biblical Studies/Christianity/John 2

Annotation of N.T.
Why change the verse? example — 2:23 Judeans do sometimes designate their celebrations as Festivals. Suggest return to original "Feast" and maybe "witnessing" instead of watching miracles. Passover revolves around the food or festive meal, others could be, for example, Celebration of Tabernacles. Athrash 05:58, 7 Apr 2005 (UTC) (few changes since page was up for deletion, evidently on technicalities)

Finalized
Findings: ευρεσις
 * Add "yearly" terminology to Passover of v. 13 because only the Gospel of John gives the length of Jesus' ministry by enumerating three Passovers.
 * Greek lessons for beginners when under edit mode the Greek words of the Word Pictures are spelled out as &alpha: to &omega: rather than ISO numbers &#945: to &#969:
 * The buildup of Capernaum, Kapharnaoum, Kephar nahûm (village of Nahum) and what happened there.
 * Notice an additional bracketed [inline footnote] wherein [prophetic] is appended to words in v. 22. Jesus alludes to himself as a prophet without honor in His own country and also added, no real prophet of the region would perish outside Jerusalem. So the thought here, an afterthought is forethought, stating the obvious.
 * The Aramism of v. 23 using the name meaning the person (Acts 1: 15) is the most important sidebar to this translation playing a role in the whole parallel outline considering Aramaic not as primacy but the tie that binds, the original spoken language, part of the oral gospel tradition. The significance is apparent in Chapter 3 (v. 18) and looms large in Chapter 15 where name (v. 21) again becomes "name of Jesus" as in John 1: 12.


text:
User:Cale Davis~enwikibooks

I am Cale Davis... and I am writing on this page...

title: User:Cale Davis~enwikibooks


text:
User talk:64.136.27.229

Hi there, it seems that you have taken an interest in contributing to the Pokémon wikibook. However, please be aware of our naming conventions as well as the notes from Pokémon:Contributor's Guide and move/reformat your pages as necessary. Also note that, as per our forking policy there is only one walkthrough for any game at a time, so your walkthrough at Pokémon Colosseum Walkthrough should be better suited at Pokémon:Pokémon Colosseum:Walkthrough or something similar (as per the book's naming conventions) KelvSYC 06:55, 22 Jun 2005 (UTC)

title: User talk:64.136.27.229


text:
Radiation Oncology/Cancer epidemiology

This page is for articles pertaining to general cancer epidemiology, such as the role of smoking in causing cancer, etc. This page should not be used to list the most common cancers. That should be done separately.

 * British Doctors Study (1951 - )
 * PMID 1009386 — "Mortality in relation to smoking: 20 years' observations on male British doctors." Doll R et al. Br Med J. 1976 Dec 25;2(6051):1525-36.
 * 34,440 men. Followed for 20 years. Ratio of death for smokers under age 70 was 2:1. Lung cancer incidence fell as smoking decreased.
 * This is the first study to establish a causal relationship between smoking and a number of cancers and heart disease.

Obesity

 * American Cancer Society Prevention Study II
 * PMID 12711737 — "Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults." Calle EE et al. N Engl J Med. 2003 Apr 24;348(17):1625-38.
 * Cohort study. 900,000 adults. 16 years follow-up.
 * RR for breast cancer associated with increasing body-mass index > 25. For men, RR of any cancer was 1.52 for BMI > 25.  For women, RR was 1.62 for BMI > 25.  BMI also associated with higher rates of death due to cancers of the esophagus, colon and rectum, liver, gallbladder, pancreas, kidney, non-Hodgkin's lymphoma, multiple myeloma.

 * Iowa Women's Health Study
 * PMID 8419667 — "Body fat distribution and 5-year risk of death in older women." Folsom AR et al. JAMA. 1993 Jan 27;269(4):483-7.
 * Cohort study. 21,707 women. Follow-up 7 years.
 * Increased breast cancer mortality with increased waist-hip ratio.

Smoking
Lung Cancer:
 * PMID 16189363, 2005 — "Effect of smoking reduction on lung cancer." Godtfredsen NS et al. JAMA. 2005 Sep 28;294(12):1505-10.

title: Radiation Oncology/Cancer epidemiology


text:
User talk:60.176.91.59

Please stop. If you continue to use Wikibooks for advertising, you will be temporarily blocked from editing.

title: User talk:60.176.91.59


text:
Cookbook talk:Paella Valenciana

I ignore who wrote this recipe, but had to be Valencian like myself.

Full thumbs up on this. —The preceding unsigned comment was added by 81.241.236.40 (talk • contribs) 2005-06-22T19:42:46.

 * Yes, he is Valencian, I can tell, and everything has been kept unaltered, except from the red wine. I've never seen anyone (at least anyone who is not drunk) pouring red wine into a paella. —The preceding unsigned comment was added by 158.42.184.155 (talk • contribs) 2007-01-30T02:00:18.

Paellera isn't correct
The name of the pan itself is paella. Paellera isn't the correct term. —The preceding unsigned comment was added by 80.36.45.46 (talk • contribs) 2007-02-22T04:14:02.

 * Whilst paella is Valencian for frying pan, paellera has come to mean "paella pan" throughout most of Spain. See the Wikipedia page on paella. Webaware talk 00:04, 22 February 2007 (UTC)

Changes to recipe
This recipe has undergone considerable changes since the above comments were made. They no longer apply. Please ignore them and have a look at the recipe. Moby-Dick4000 (talk) 02:46, 4 August 2009 (UTC)

Garlic
Garlic is not an ingredient in Valencian (meat) paella. I have changed it to "(seldom)".
 * There are prominent Valencian chefs who use garlic and others who don't. I believe, therefore, the correct word here is optional. Moby-Dick4000 (talk) 22:26, 12 May 2010 (UTC)

To anon user 76.121.3.20
I reverted your change regarding usage of the word paella for the following reason: The word paella means pan only in Spain's Valencian community. Paellera is the word for the wide shallow pan used to make paella in all other parts of the world, including Spain outside of Valencia. Also, the Royal Spanish Academy, the organization which regulates the Spanish language, defines both words as correct for the pan. Please see these links:
 * http://buscon.rae.es/draeI/SrvltConsulta?TIPO_BUS=3&LEMA=paellera
 * http://buscon.rae.es/draeI/SrvltConsulta?TIPO_BUS=3&LEMA=paella

Moby-Dick4000 (talk) 22:23, 12 May 2010 (UTC)

title: Cookbook talk:Paella Valenciana


text:
User talk:24.130.60.200

Hello and welcome to Wikibooks!

Here are some tips to help you get started:

 * Remember to conduct any editing experiments in the sandbox.
 * Check out our help page if you need additional help.
 * Eventually, you might want to read the Manual of Style and Policies and Guidelines.
 * Remember to maintain a Neutral point of view.
 * Explore, be bold in editing pages, and have fun!

Good luck!

(Donovan|Geocachernemesis|Interact) 10:16, 22 Jun 2005 (UTC)

title: User talk:24.130.60.200