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George A Ricaurte, Jr, M.D., Ph.D.

• Professor of Neurology

https://www.hopkinsmedicine.org/profiles/results/directory/profile/0002417/george-ricaurte

Helping pet owners with the eu istration of a local anesthetic and electrical dehorning on thanasia decision medications 7 cheap levaquin 250mg with mastercard. Comparison of four regimens for in medicine: delivering bad news and euthanasia decision mak traoral administration of medication to induce sedation in ing symptoms jaw bone cancer generic 250mg levaquin visa. The language of the horse: habits and forms of thanasia rates medicine zebra order 750 mg levaquin fast delivery, euthanasia practices medicine 93 7338 cheap 500 mg levaquin with visa, and human resource expression cold medications buy 500mg levaquin with amex. The caringkill jective and objective assessments of stress at slaughter and ing paradox: euthanasiarelated strain among animal shelter meat quality in pigs symptoms 0f parkinson disease buy levaquin cheap. Laboratory animal technicians: their role in stress and equipment problems in slaughter plants. Pheromonal transmission how animal behavior affects the perspectives of caregivers. Improving the wellbeing of farm animals: maxi awareness during dexmedetomidine and propofol induced mizing welfare and minimizing pain and suffering. Denver: American Hu Council for the Care of Animals in Research and Teaching, mane Association, 2010. The suitability of any particular inhaled agent for Distress during administration of inhaled agents euthanasia therefore depends largely on distress and/ has been evaluated by means of both behavioral as or pain experienced prior to loss of consciousness. While overt behavior Distress can be caused by handling, specifc agent al signs of distress have been reported in some stud properties, or method of administration, such that a ies, others have not consistently found these effects. Suf Through preference and approachavoidance testing, fering can be conceptualized as the product of severi all inhaled agents currently used for euthanasia have ty, incidence, and duration. The conditions of exposure used for agent or condition that results in rapid unconscious aversion studies, however, may differ from those used ness with few or no outward signs of distress. In addition, agents identifed goal is to identify best practices for administering as being less aversive (eg, Ar or N2 gas mixtures, in inhaled agents, defning the optimal conditions for haled anesthetics) can still produce overt signs of be transport, handling, and agent selection and delivery havioral distress (eg, openmouth breathing) in some to produce the least aversive and distressing experi species under certain conditions of administration ence for each species. The desired fnal concen As for physical methods, the conditions under tration will be achieved more quickly by using a which inhaled agents are administered for euthana greater displacement rate (see M1. However, for many agents and spe istered under conditions where animals are most cies, forced exposure to high concentrations can comfortable (eg, for rodents, in a darkened home be aversive and distressing, such that gradual ex cage9; for pigs, in small groups). If animals need posure may be the most pragmatic and humane to be combined, they should be of the same spe option. Chambers should not be from a commercially supplied source, cylinder, overloaded and need to be kept clean to mini or tank, such that an effective displacement rate mize odors that might cause distress in animals and/or concentration can be readily quantifed. The direct application of products of combustion (11) Because some inhaled agents may be lighter or or sublimation is not acceptable due to unreliable heavier than air, layering or loss of agent may or undesirable composition and/or displacement permit animals to avoid exposure. Chambers and contain haled agents must be in good working order and ers should be as leak free as possible. This can be done either by tressful death and may be hazardous to other ani examination of individual animals or by adher mals and to personnel. These likely because the rise in alveolar gas concentra processes are commonly combined in the practice of tion is delayed. A similar delayed rise in alveolar anesthesia to predict how quickly a change in con gas concentration can be observed in excited an centration of an inhaled anesthetic will occur within imals having increased cardiac output. Conversely, for the washout ex induction of anesthesia and time to loss of con ponential function the quantity under consideration sciousness when inhaled agents are used may be falls at a rate that progressively decreases in propor greatly prolonged. Again, in theory, nasia should be considered for these species and the quantity approaches, but never reaches, zero. If cally equal to the enclosed volume or space undergo high fows are required, equipment should be de ing washin or washout divided by the rate of fow, signed to minimize noise and gas streams blow or displacement, into that space, where fi = volume/ ing directly on the animals. Although a complete description of the op concentration of the infowing gas to rise to 63. Unlike fi(fi) required for the gas concentration within the immersion, animals are introduced at a controlled container to equal the infowing gas concentration. The fow, halothane, methoxyfurane, isofurane, sevofurane, or displacement rate, therefore determines the time desfurane, enfurane) have been used to euthanize constant for any given enclosed volume, such that many species. Hal Based on ure 3, it can be shown that a gradual othane induces anesthesia rapidly and is an effective infow or displacement rate of 20% of the chamber inhaled agent for euthanasia. Enfurane is less soluble volume/minute represents a time constant (fi) value in blood than halothane, but, because of its lower va of 5 minutes (1 divided by 0. At deep anesthetic rate equivalent to 20% of the chamber volume/min, planes, convulsions may occur. Similarly, isofurane or halothane and has a lower vapor pres Niel and Weary17 reported 65% after 340 seconds (1fi) sure. Although sevofurane is reported to methods will require displacement rates of 3fi to at possess less of an objectionable odor than isofurane, tain 95% of the infow gas concentration within the some species may struggle violently and experience chamber. This drug is so volatile that it could displacement rate for the size container being utilized displace O2 and induce hypoxemia during induction is absolutely necessary when compressed gases are if supplemental O2 is not provided. By reducing high pressure eyes, nose, and respiratory airways; poses serious at the cylinder valve, gas fow is made constant to the risks due to fammability and explosiveness; and has fow meter as cylinder pressure decreases during use. Aversion to nated inhaled anesthetics are not to exceed 2 ppm inhaled anesthetics increases following initial expo (1hour ceiling) when used alone, or 0. Because the liquid state of most ppm for enfurane for an 8hour timeweighted expo inhaled anesthetics is irritating, animals should be ex sure. With inhaled anesthetics, ani they were found to be attainable utilizing clinical mals can be placed in a closed receptacle containing scavenging techniques and there are no controlled cotton or gauze soaked with an appropriate amount studies proving exposure at these concentrations of liquid anesthetic33 or anesthetic vapor can be in are safe. Induction time will be infuenced by dial setting, cupational Safety and Health Administration has no fow rate, and size of the container; time to death may permissible exposure limits regulating these specifc be prolonged because O2 is commonly used as the agents. Suffcient air or ministered by several different methods depending O2 must be provided during the induction period to on the circumstances and equipment available (eg, prevent hypoxia. In humans, the minimum alveolar con anesthetics can be useful as the sole euthanasia agent centration (defned as the median effective dose) for or as part of a 2step process, where animals are frst N2O is 104%; its potency in other species is less than rendered unconscious through exposure to inhaled half that in humans (ie, approx 200%). Because the anesthetic agents and subsequently killed via a sec effective dose for N2O is above 100%, it cannot be ondary method. Animals may struggle distressed prior to loss of consciousness when N2O is and become anxious during induction of anesthesia, used as the sole agent. Up to 70% N2O may be com with some animals exhibiting escape behaviors prior bined with other inhaled gases to speed the onset of to onset of unconsciousness. Learned aversion to in anesthesia; however, the anesthetic contribution of haled anesthetics occurs in rodents. Should apnea or N2O will be only half (20% to 30%) of that expected excitement occur, time to loss of consciousness may in humans due to its reduced potency in animals. The frst 2 techniques are associated concentration will have on the time constant and rate with substantial problems such as production of oth of rise of anesthetic concentration. Nitrous oxide caused collapse in 1 minute, cessation of breathing should not be used alone. Ether is not acceptable for eutha and behavioral characteristics of dogs exposed to 6% nasia. It is not clear whether these (5) Neonatal animals will require extended exposure behavioral responses are indicative of animal dis times. If animals need to be combined, they should exposed to gradually decreasing concentrations of O2 be of the same species, and, if needed, restrained or and increasing concentrations of Ar, they always left separated so that they will not hurt themselves or oth the chamber before losing consciousness (typically ers. When direct application of products of combustion or sub Ar was used to euthanize chickens, exposure to a limation is not acceptable due to unreliable or unde chamber preflled with Ar, with an O2 concentration sirable composition and/or displacement rate. Contin and fow meter combination or equivalent equipment ued exposure led to convulsions at 20 to 24 seconds. Use of Ar or N2 is unacceptable for Pigs chose to place their head in a hypoxic (< 2% other mammals. These gases create an anoxic envi O2, 90% Ar) chamber containing a food reward, re ronment that is distressing for some species and aver mained with their head in the chamber until they sive to laboratory rodents and mink; other methods became ataxic, and freely returned to the chamber of euthanasia are preferable for these species. The direct application of products of combus Mink will also enter into a hypoxic chamber (< tion or sublimation is not acceptable due to unreli 2% O2, 90% Ar), but will not remain until the point of able or undesirable composition or displacement rate. The duration of hypoxic exposure As gas displacement rate is critical to the humane freely chosen is similar to the average duration of a application of these gases, an appropriate pressure dive for mink, suggesting they are able to detect hy reducing regulator and fow meter combination or poxia and modify their behavior to avoid detrimental equivalent equipment with demonstrated capability effects. Loss of consciousness will be preceded stimulation of ion channels within the amygdala asso by openmouth breathing and hyperpnea, which may ciated with the fear response. Using an 2 which was suffcient to render them recumbent, un approachavoidance model, a preliminary study by conscious, and unresponsive, and observed 10fold in Withrock et al130 suggests that dairy goat kids exhibit creases in vasopressin and oxytocin concentrations. As a general rule, a gentle death that takes longer In rats, unconsciousness is induced in approximately is preferable to a rapid, but more distressing death. If an appropri ber volume/minute) induces unconsciousness in only ate gradual displacement rate is used, animals will 26 to 48 seconds. By 10 days of age, exposure times of 5 minutes same report, time to loss of somatosensory evoked were suffcient to ensure death. However, mice and rats also show evidence of displacement rate from 30% to 70% of the chamber learned aversion to inhaled anesthetic agents and are volume/min is recommended for rodents. Because large amounts of inhaled anesthetics be combined, they should be of the same species are absorbed and substantial amounts remain in the and, if needed, restrained so that they will not hurt body for days, even after apparent recovery, 40 eutha themselves or others. A 2step process, (2) Carbon dioxide is readily available in compressed where animals are frst rendered unconscious and gas cylinders. The direct dioxide, whether administered by prefll or gradual application of products of combustion or sublimation displacement methods, can be aversive to some spe is not acceptable due to unreliable or undesirable cies, and therefore potential exists to cause distress. It is usually the most desirable method when it can be performed without causing fear or distress in the animal. The primary routes of their administration are awareness for personnel safety is imperative when parenteral injection, topical application, and immer using injectable euthanasia agents because needle sion. When it is being determined whether a particu stick injuries involving these drugs have been shown lar drug and route of administration are appropriate to result in adverse effects (41. When not feasible, euthanasia agents com their infuence remain awake and able to feel pain. Paralytic immobilizing agents must never be used as Disposal of euthanized animals has become increas a sole means of euthanasia, nor should they be used ingly problematic because most rendering facilities if delay is expected between immobilization and eu will no longer take animals euthanized with agents thanasia. In laboratory rats, addi by other animals is possible153 or when euthanized tion of lidocaine or bupivacaine to pentobarbital re animals are fed to zoo and exotic animals. Exceptions include animals with or intrarenal injections are acceptable only when highly permeable skin to which nonirritating, rapidly performed on anesthetized or unconscious animals absorbed agents are applied (eg, amphibians eutha (with the exception of intrahepatic injections in cats nized with benzocaine gel). In some poikilotherms for the oral route has several disadvantages when which intracardiac puncture is the standard means of considered for administration of euthanasia agents, vascular access (eg, some snakes and other reptiles), including lack of established drugs and doses, vari intracardiac administration of euthanasia solutions ability in agent bioavailability and rate of absorption, in awake animals is acceptable. For these reasons, the intrathecal, and other nonvascular injections are not oral route is unacceptable as a sole means of euthana acceptable routes of administration for injectable eu sia. With an anatomic characteristics, optimal methods for deliv overdose, deep anesthesia progresses to apnea due to ery of euthanasia agents will vary. In many situations, depression of the respiratory center, and this is fol the immersion of aquatic animals in water contain lowed by cardiac arrest. Immersion agents added able barbiturates are those that are potent, nonirritat to water may be absorbed by multiple routes, includ ing, long acting, stable in solution, and inexpensive. More research into the ef nonirritating to skin, eyes, and oral and respiratory fcacy, speed of action, and nociceptive responses tissues and will result in rapid loss of consciousness of nonvascular routes of barbiturate euthanasia solu (often, but not always, measured as a loss of righting tions is needed before changes in recommendations response) with minimal signs of distress or avoidance for these alternate routes can be made. Subse using barbiturates for euthanasia in dogs and cats far quently, chloroquine phosphate, an antimalarial drug outweigh the disadvantages. Intravenous injection of with profound cardiovascular depressant effects, was a barbituric acid derivative is the preferred method added to embutramide, and studies verifed a signif cantly shorter time until death. Barbiturates are also acceptable for all other but when tested for euthanasia of cats, a substantial species of animals if circumstances permit their use. The addition of chloroquine tressful, dangerous, or diffcult due to small patient and lidocaine also lowers the dosage of embutramide size. This effect depends on the dose, concentra (eg, phenytoin, ethanol), or agents that metabolize tion, route, and rate of the injection. Although some of the additives are duces euthanasia smoothly, with minimal discomfort slowly cardiotoxic, euthanasia makes this pharma to the animal. The pharmacologic properties and rec in dogs, it is not currently being manufactured. Carfentanil has been used transmucosally in a lol extralabel use in cats is also acceptable. However, electrophysi of euthanized animals are ingested; therefore proper ologic studies in dogs and rabbits have shown that disposal of animal remains is essential. Personnel han seen during the induction phases of anesthesia, the dling the drugs must be familiar with their hazards, behavior demonstrated during these reactions can and a second person must be standing by and be pre cause distress in personnel witnessing euthanasia.

As members of several intersecting minority groups symptoms gallbladder problems discount 500 mg levaquin with visa, transgender people of color treatment 1 degree burn buy 750mg levaquin with mastercard, and transgender women of color in particular symptoms 6dp5dt generic levaquin 250mg with mastercard, are especially vulnerable to employment discrimination treatment 6th feb cardiff purchase levaquin with amex, poor health outcomes treatment refractory purchase levaquin line, harassment treatment tracker buy generic levaquin 250mg online, and violence. Consequently, they face even greater obstacles than white transgender individuals and cisgender members of their own race. Results indicated that participants who identified as transgender and gender nonconforming had significantly higher levels of anxiety and depression than those identifying as cisgender. The transgender children discussed in chapter 4 may, when they become an adult, alter their bodies through medical interventions, such as surgery and hormonal therapy, so that their physical being is better aligned with gender identity. However, not all transgender individuals choose to alter their bodies or physically transition. Many will maintain their original anatomy but may present themselves to society as a different gender, often by adopting the dress, hairstyle, mannerisms, or other characteristics typically assigned to a certain gender. It is important to note that people who crossdress, or wear clothing that is traditionally assigned to the opposite gender, such as transvestites, drag kings, and drag queens, do not necessarily identify as transgender (though some do). Sexuality may be experienced and expressed in a variety of ways, including thoughts, fantasies, desires, beliefs, attitudes, values, behaviors, practices, roles, and relationships. These may manifest themselves in biological, physical, emotional, social, or spiritual aspects. The biological and physical aspects of sexuality largely concern the human reproductive functions, including the human sexualresponse cycle and the basic biological drive that exists in all species. Emotional aspects of sexuality include bonds between individuals that are expressed through profound feelings or physical manifestations of 258 love, trust, and care. Sexuality also impacts, and is impacted by cultural, political, legal, philosophical, moral, ethical, and religious aspects of life. In most mammalian species, sex hormones control the ability to engage in sexual behaviors. However, sex hormones do not directly regulate the ability to copulate in primates (including humans); rather, they are only one influence on the motivation to engage in sexual behaviors. Social factors, such as work and family, also have an impact, as do internal psychological factors like personality and stress. Sex drive may also be affected by hormones, medical conditions, medications, lifestyle stress, pregnancy, and relationship issues. The sexual response cycle is a model that describes the physiological responses that take place during sexual activity. According to Kinsey, Pomeroy, and Martin (1948), the cycle consists of four phases: excitement, plateau, orgasm, and resolution. The excitement phase is the phase in which the intrinsic (inner) motivation to pursue sex arises. The plateau phase is the period of sexual excitement with increased heart rate and circulation that sets the stage for orgasm. Orgasm is the release of tension, and the resolution period is the unaroused state before the cycle begins again. The Brain and Sex: the brain is the structure that translates the nerve impulses from the skin into pleasurable sensations. The brain regulates the release of hormones, which are believed to be the physiological origin of sexual desire. The cerebral cortex, which is the outer layer of the brain that allows for thinking and reasoning, is believed to be the origin of sexual thoughts and fantasies. Beneath the cortex is the limbic system, which consists of the amygdala, hippocampus, cingulate gyrus, and septal area. These structures are where emotions and feelings are believed to originate, and they are important for sexual behavior. This is the small area at the base of the brain consisting of several groups of nervecell bodies that receives input from the limbic system. Studies with lab animals have shown that destruction of certain areas of the hypothalamus causes complete elimination of sexual behavior. One of the reasons for the importance of the hypothalamus is that it controls the pituitary gland, which secretes hormones that control the other glands of the body. Oxytocin, also known as the hormone of love, is released during sexual intercourse when an orgasm is achieved. Oxytocin is also released in females when they give birth or are breast feeding; it is believed that oxytocin is involved with maintaining close relationships. In males, testosterone appears to be a major contributing factor to sexual motivation. Vasopressin is involved in the male arousal phase, and the increase of vasopressin during erectile response may be directly associated with increased motivation to engage in sexual behavior. The relationship between hormones and female sexual motivation is not as well understood, largely due to the overemphasis on male sexuality in Western research. Estrogen and progesterone typically regulate motivation to engage in sexual behavior for females, with estrogen increasing motivation and progesterone decreasing it. Research suggests that testosterone, oxytocin, and vasopressin are also implicated in female sexual motivation in similar ways as they are in males, but more research is needed to understand these relationships. Sexual Responsiveness Peak: Men and women tend to reach their peak of sexual responsiveness at different ages. For men, sexual responsiveness tends to peak in the late teens and early twenties. Sexual arousal can easily occur in response to physical stimulation or fantasizing. Sexual responsiveness begins a slow decline in the late twenties and into the thirties, 260 although a man may continue to be sexually active. Through time, a man may require more intense stimulation in order to become aroused. Women often find that they become more sexually responsive throughout their 20s and 30s and may peak in the late 30s or early 40s. This is likely due to greater selfconfidence and reduced inhibitions about sexuality. Proper use of safesex supplies (such as male condoms, female condoms, gloves, or dental dams) reduces contact and risk and can be effective in limiting exposure; however, some disease transmission may occur even with these barriers. Historically, religion has been the greatest influence on sexual behavior in the United States; however, in more recent years, peers and the media have emerged as two of the strongest influences, particularly among American teens (Potard, Courtois, & Rusch, 2008). Mass media in the form of television, magazines, movies, and music continues to shape what is deemed appropriate or normal sexuality, targeting everything from body image to products meant to enhance sex appeal. Cultural Differences: In the West, premarital sex is normative by the late teens, more than a decade before most people enter marriage. In the United States and Canada, and in northern and eastern Europe, cohabitation is also normative; most people have at least one cohabiting 261 partnership before marriage. In southern Europe, cohabiting is still taboo, but premarital sex is tolerated in emerging adulthood. In contrast, both premarital sex and cohabitation remain rare and forbidden throughout Asia. Even dating is discouraged until the late twenties, when it would be a prelude to a serious relationship leading to marriage. In crosscultural comparisons, about three fourths of emerging adults in the United States and Europe report having had premarital sexual relations by age 20, versus less than one fifth in Japan and South Korea (Hatfield & Rapson, 2006). It is a personal quality that inclines people to feel romantic or sexual attraction (or a combination of these) to persons of a given sex or gender. Sexual orientation is independent of gender; for example, a transgender person may identify as heterosexual, homosexual, bisexual, pansexual, polysexual, asexual, or any other kind of sexuality, just like a cisgender person. Research done over several decades has supported this idea that sexual orientation ranges along a continuum, from exclusive attraction to the opposite sex/gender to exclusive attraction to the same sex/gender (Carroll, 2016). Bisexuality was a term traditionally used to refer to attraction to individuals of either male or female sex, but it has recently been used in nonbinary models of sex and gender. Alternative terms such as pansexuality and polysexuality have also been developed, referring to attraction to all sexes/genders and attraction to multiple sexes/genders, respectively (Carroll, 2016). Being asexual is not due to any physical 262 problems, and the lack of interest in sex does not cause the individual any distress. Development of Sexual Orientation: According to current scientific understanding, individuals are usually aware of their sexual orientation between middle childhood and early adolescence. However, this is not always the case, and some do not become aware of their sexual orientation until much later in life. It is not necessary to participate in sexual activity to be aware of these emotional, romantic, and physical attractions; people can be celibate and still recognize their sexual orientation. Some researchers argue that sexual orientation is not static and inborn but is instead fluid and changeable throughout the lifespan. There is no scientific consensus regarding the exact reasons why an individual holds a particular sexual orientation. However, biological explanations, that include genetics, birth order, and hormones will be explored further as many scientists support biological processes occurring during the embryonic and and early postnatal life as playing the main role in sexual orientation (Balthazart, 2018). Bailey and Pillard (1991) studied pairs of male twins and found that the concordance rate for identical twins was 52%, while the rate for fraternal twins was only 22%. Bailey, Pillard, Neale, and Agyei (1993) studied female twins and found a similar difference with a concordance rate of 48% for identical twins and 16% for fraternal twins. Schwartz, Kim, Kolundzija, Rieger, & Sanders (2010) found that gay men had more gay male relatives than straight Source men, and sisters of gay men were more likely to be lesbians than sisters of straight men. Fraternal Birth Order: the fraternal birth order effect indicates that the probability of a boy identifying as gay increases for each older brother born to the same mother (Balthazart, 2018; Blanchard, 2001). A metaanalysis indicated that the fraternal birth order effect explains the sexual orientation of between 15% and 29% of gay men. Hormones: Excess or deficient exposure to hormones during prenatal development has also been theorized as an explanation for sexual orientation. In 263 contrast, too little exposure to prenatal androgens may affect male sexual orientation by not masculinizing the male brain (Carlson, 2011). Sexual Orientation Discrimination: the United States is heteronormative, meaning that society supports heterosexuality as the norm. Consider, for example, that homosexuals are often asked, "When did you know you were gayfi Living in a culture that privileges heterosexuality has a significant impact on the ways in which nonheterosexual people are able to develop and express their sexuality. It can be expressed as antipathy, contempt, prejudice, aversion, or hatred; it may be based on irrational fear and is sometimes related to religious beliefs (Carroll, 2016). Homophobia is observable in critical and hostile behavior, such as discrimination and violence on the basis of sexual orientations that are non heterosexual. Sexual minorities regularly experience stigma, harassment, discrimination, and violence based on their sexual orientation (Carroll, 2016). Research has shown that gay, lesbian, and bisexual teenagers are at a higher risk of depression and suicide due to exclusion from social groups, rejection from peers and family, and negative media portrayals of homosexuals (Bauermeister et al. Discrimination can occur in the workplace, in housing, at schools, and in numerous public settings. Major policies to prevent discrimination based on sexual orientation have only come into effect in the United States in the last few years. This demographic limits our understanding of more 264 marginalized subpopulations that are also affected by racism, classism, and other forms of oppression. The hallmark of this type of thinking is the ability to think abstractly or to consider possibilities and ideas about circumstances never directly experienced. If you compare a 15 yearold with someone in their late 30s, you would probably find that the latter considers not only what is possible, but also what is likely. The adult has gained experience and understands why possibilities do not always become realities. They learn to base decisions on what is realistic and practical, not idealistic, and can make adaptive choices. This advanced type of thinking is referred to as Postformal Thought (Sinnott, 1998). Dialectical Thought: In addition to moving toward more practical considerations, thinking in early adulthood may also become more flexible and balanced. Abstract ideas that the adolescent believes in firmly may become standards by which the adult evaluates reality. Adolescents tend to think in dichotomies; ideas are true or false; good or bad; and there is no middle ground. However, with experience, the adult comes to recognize that there is some right and some wrong in each position, some good or some bad in a policy or approach, some truth and some falsity in a particular idea. This ability to bring together salient aspects of two opposing viewpoints or positions is referred to as dialectical thought and is considered one of the most advanced aspects of postformal thinking (Basseches, 1984). Such thinking is more realistic because very few positions, ideas, situations, or people are completely right or wrong. So, for example, parents who were considered angels or devils by the adolescent eventually become just people with strengths and weaknesses, endearing qualities, and faults to the adult. Formal operational thought involves being able to think abstractly; however, this ability does not apply to all situations or all adults. Some adults lead lives in which they are not challenged to think abstractly about their world. Many adults do not receive any formal education and are not taught to think abstractly about situations they have never experienced. Further, they are also not exposed to conceptual tools used to formally analyze hypothetical situations. Those who do think abstractly may be able to do so more easily in some subjects than others.

Researchers stress that behavioral skills training is an effective method of teaching prevention skills to individuals with disabilities symptoms 0f diabetes purchase generic levaquin on line, but this hypothesis is supported only by studies of behavioral skills training of children (Lumley & Miltenberger treatment zygomycetes generic 500 mg levaquin overnight delivery, 1997) treatment 0f osteoporosis buy levaquin 250 mg amex. It is clear that additional research examining effectiveness of prevention programs specifically for this population is necessary before any definite conclusions can be drawn medicine nelly purchase generic levaquin pills. Synthesis of Effectiveness Evidence this section provides a summary of the key characteristics of the nine studies of individuals with disabilities that met inclusion criteria (see chapter 3) for this evidencebased review hair treatment buy levaquin 750 mg online. Descriptive Information the complete results of the data abstraction process for each of the nine studies examining individuals with disabilities are presented in appendix E symptoms 24 buy 750mg levaquin overnight delivery. Six studies examined individuals with mild to severe mental retardation, two studies examined individuals with learning disabilities, and one study examined a deaf individual and an individual living in a treatment center for developmentally delayed individuals. The majority of studies (n=6) included only females participants; the other three studies included both males and females. Two studies reported assessment of past victimization and two studies reported sexual activity of the study participants. Eight of the nine studies assessed level of learning disability (mild, moderate, or severe) to ensure that the participants had adequate communication and language skills required to participate. Three of the studies assessed whether individuals had received previous training in the prevention of sexual abuse. Of the six studies that reported clear information about length of the program length, four studies consisted of 10 or fewer intervention contact hours with participants; of the other three studies, one provided the number of sessions without the length, one provided the length of sessions without the total number of sessions, and one did not report on the time frame of the intervention. Of the four study designs identified (pretest/posttest design, nonequivalent comparison group design, randomized comparison group design, and experimental design), the most common study design was the pretest/posttest design, which six studies used. All the studies had relatively small sample sizes ranging from 2 to 77 participants; the majority of studies (n=6) had fewer than 10 participants. Followup assessment was conducted in eight of the studies, ranging from 1 month to 8 years since completion of the intervention. Study retention rates, which reflect the number of baseline participants who participated in followup data collection periods, ranged from 60 to 100 percent. All of the studies used a posttest, and the majority of studies (n=7) had posttest retention rates greater than 75 percent. Four of the eight studies that included a followup assessment had followup retention rates greater than 75 percent. The majority of studies (n=7) measured skills/strategies for preventing sexual abuse, and more than half (n=5) measured knowledge of prevention strategies. Two studies examined the side effects of the intervention; and one study each, in addition to examining either knowledge or skills, F8 this document is a research report submitted to the U. Study measures were diverse; five studies used authordeveloped measures, with little information regarding psychometric properties. It is important to consider information about the intervention and the manner in which the assessment was conducted when interpreting the findings. Three of the seven studies that conducted skills training delivered corrective feedback to respondents on their skills performance (nos. Because five of the studies conducted the intervention until the desired response was achieved (at which time the training was considered complete), the results of the final followup for these studies always indicated a positive intervention effect (nos. Positive effects were reported among the four studies for skills and knowledge as well. Additional studies that measure effectiveness need to be conducted to fully understand and develop meaningful inferences. These suggestions, discussed below, provide useful information to guide future prevention efforts in the areas of practice and research. The majority of researchers identified the lack of appropriate assessment tools as a significant barrier to examining effectiveness and suggested the development of alternative assessment methods. More naturalistic settings and assessment tools to examine effectiveness in real life are hypothesized to provide more valid measurements of preventive effects. Enhancing program curricula and presentation may also provide more insight into prevention efforts for this F9 this document is a research report submitted to the U. Authors suggested that program effectiveness may be enhanced by employing more diverse strategies, such as training approaches for both cognitive and motivational issues in decision making and broader topic areas including sex education, societal norms, and familial and peer pressure, as well as by increasing the number of sessions provided. Developmentally appropriate material that individuals enjoy and actively engage in at a suitable pace will help ensure active participation of the target audience. In addition, support and acceptance of program staff and teachers are crucial to the success of a program. Researchers indicate that future research must identify elements of the intervention that are essential and effective. Identifying commonalities among sexually active adolescents and the impact of refusal skills on unwanted sexual behavior are essential to developing any meaningful conclusions. Furthermore, increasing the number of followup assessments and using more than one independent rater to observe skill acquisition will increase reliability in measuring effectiveness. Small sample sizes across the studies make it difficult to generalize for the larger population of individuals with disabilities, and the combination of individuals with different disabilities. Corrective feedback strategies which were implemented in the majority of the studies, made it difficult to assess whether the respondents learned new skills and maintained them over a longer period of time. Conclusion Although the majority of the studies reviewed in this report indicated positive results in skill and knowledge acquisition, the findings are inconclusive because of the limited amount of research on sexual assault/abuse prevention for individuals with disabilities. Researchers emphasize the need to develop more appropriate assessment tools and enhance curriculum components as crucial strategies for improving prevention efforts targeting this vulnerable population. Additional studies employing these advances are critical to our understanding of how to effectively prevent sexual assault among individuals with disabilities. Gender Length Intervention Content Incentives Study Design Size Sample Size Measures 72 Females 1. A review and critique of research evaluation child sexual abuse prevention programs. The sexual knowledge, experience, feelings, and needs of people with mild intellectual disability. Education and Training in Mentally Retardation and Developmental Disabilities, 31, 1321. Sexual Abuse Prevention Strategies and Programs for Persons with Developmental Disabilities. Sexual victimization of people with disabilities: Professional and social responsibilities. Sexual abuse and exploitation of children and adults with mental retardation and other handicaps. Sex:100% fem ale Sam pling F ram eSize:N otreported Participantsprovidedwithfastfoodcouponsforcorrect perform anceonafix edratiobasis. E ducation:N otreported BaselineSam pleSize(andP articipationR ate): 5wom en(ratenotavailable) Curriculum /Content:Involvedbehavioralskillstraining R ace/E thnicity:N otreported withpairsof wom en(ex ceptforonewom anwhowas P osttestandF ollowup Sam pleSizes(and trainedindividually);involvedpresentationof inform ation SexuallyActive:N otreported P articipationR ates): aboutsex ualbehaviorandsex ualabuse;training to Posttest:4/5= 80% discrim inatesex ualabusefrom innocuoussituations, V ictim ization:N otreported F ollowup:4/5= 80% instructionsintheuseof thesex ualabuseprevention skillsinresponsetoasex ualsolicitationfrom astaff Crim inalHistory:N otreported T im eP ointsof D ataCollection: person, rehearsalof theskillsinroleplaysof asex ual Pretest(priortotraining tim enotreported) solicitation;praisesforcorrectperform anceand O ther(i. G eneraliz ationwasassessedviainsite assessm entsinwhichanunknownm aleresearchassistant Assessm entof E xposure:O nly5wom enin whowasintroducedasanew staff person, presenteda intervention;staff knew if theywereinattendance solicitation InterventionR etentionR ate:80% O ther: G 3 this document is a research report submitted to the U. M easures R esults StudyQ uality K nowledg e:4to10verbalreports(Ssdescribewhatshe P rim aryM easures: Q ualityScore: m ightdoinresponsestoascenariodescribedtoher) T otal:35/90(39%) O verall:thisinvestigationshowedthata10week D escription:13/25(44%) T im eP ointsof M easurem ent:pretest, during behavioralskillstraining program resultedinthe D esig n:22/65(34%) training acquisitionof sex ualabusepreventionskills, butthatthe skillsdidnotfullygeneraliz etoinsituassessm ents. V ictim ization:N otreported M ajorW eaknesses: Attitudes: Study: T im eP ointsof M easurem ent: Subjectsknew theywerebeing assessed V ictim ization: Sm allsam ple P erpetration:N otreported Shortfollowup period P erpetration: Subjectswerecoacheduntilthegavethecorrect T im eP ointsof M easurem ent: responsenotgeneraliz able. O therM easures:A 10weekbehavioralskillstraining O therM easures: program resultedintheacquisitionof sex ualabuse Article: R ole play(m easuresskills) preventionskills, buttheskillsdidnotfullygeneraliz eto D ifficulttodistillinform ationfrom article Insitu insituassessm ents. T im eP ointsof M easurem ent: Skillstraining resultedincriterionperform ance(ascoreof pretest:roleplay 4)in3consecutiveroleplayassessm entsforallSs. W ithin3daysof 2 scoresof 4ontheinsitu correctresponsesinroleplaysituations, anotherinsitu O nemonthfollowup:initialscoreswere3for3subjectsand assessm entwasconducted. Insitu:O nem onthfollowing insitutraining if the Attendance/T reatm entCom pletion:N otreported subjectreceivedascoreof 4, herparticipationinthe studywasfinished. If herscorewaslessthan4, insitu O ther: trainingswererepeateduntilsubjectreceivedascoreof 4 orbetteronasubsequentinsituassessm ent. Sex ualintercourseandsex relatedbehaviorsand theneedtouseprotectionwhensex uallyactivewere E ducation:N otreported T im eP ointsof D ataCollection: ex plained(andparticipantswereinstructedtotalktotheir Baseline:firstm eeting casem anagersforpersonalguidanceregarding R ace/E thnicity:N otreported Posttest:atendof assessm ents protection. Crim inalHistory:N otreported A ssessm entstookplaceintheparticipantsgroup hom es ex ceptforone, whosetraining andassessm enttookplace Session2:thethreecom ponentcriterionresponseof O ther(i. The 5wom enwerecategoriz edasfunctioning inthem ild trainersfirstm odeledthesebehaviorsfortheparticipants rangeof m entalretardation, and1wasinthem oderate inaroleplayform at, andtheparticipantsthentookturns range. P opulationandSetting StudyD esig nandSam ple Intervention Session3:servedtoex pandontheskillsdevelopedin Sessions1and2throughverbalreview andtheuseof a widervarietyof roleplaysituations. Session4:startedwithareview of previouslycovered m aterialandwasfollowedbyex pandedroleplaying that includedsituationsinwhichsecrets, bribes, orthreats wereusedaspartof thesex ualabuselure. Session5:consistedof areview of allm aterialcovered andtheuseof variedroleplaying situationsthatdealt withallof theconceptsincludedasathreat. P rog ram Im plem enter:training wasadm inisteredbya team of onem aleandonefem aletrainer. T rainers includedonefem aleandtwofem alegraduatestudents andonefem aleundergraduatestudentinpsychology. CulturallySpecific:N otreported Assessm entof E xposure:O nly6wom enin intervention;staff knew if theywereinattendance InterventionR etentionR ate:100% O ther: M easures R esults StudyQ uality K nowledge:N ineclosedendquestionsasking whethera P rim aryM easures: Q ualityScore: particularsex ualbehavior. In K nowledg e:averagescoreonpretestwas67% and84% D escription:16/25(64%) addition, participantswereaskedif nonsex ualtypesof ontheposttest. Attitudes: M ajorStreng ths: V ictim ization: Study: G 6 this document is a research report submitted to the U. M easures R esults StudyQ uality T im eP ointsof M easurem ent: P erpetration: responsestoverbalreportwerereviewedindependently O ncebeforetraining bytworeviewers. A safescenario, inwhich dem onstratedthecriterionresponseontheverbalreport Study: thetrainerdescribedasituationthatdidnotinvolve m easure. The notsurewhosam plerepresents participantwasthankedfortheirresponsetothe R oleplaying: scenarios, butnospecificfeedbackwasprovided. The following training:allbutoneof theparticipants(83%) responseswererecordedbythetrainerandwerelater m ovedtocriterionperform ance reviewedindependentlybytworesearchers. A scorewas O nem onthaftertraining:5of thesix (83%) assignedfortheresponsetothesex ualabusescenario dem onstratedthethreecom ponentcriterionresponse according tothe4pointscale. T im eP ointsof M easurem ent: T hesescenarioswere N aturalisticProbes: presentedduring eachbaselineassessm entandpriorto following treatm ent:participantsfailedtoachievecriterion eachtraining session. Attitudes:N otreported O nem onthaftertreatm ent:noparticipantsachieved criterionperform anceonthism easure, dem onstrating the T im eP ointsof M easurem ent: lackof generaliz ationof theskillstothetargetsituation. V ictim ization:N otreported Sideeffectsquestionnaire:posttraining m eanswereslightly lowerthanthepretraining m eans. T im eP ointsof M easurem ent: P erpetration:N otreported Q uestionnaireregarding satisfactionwithprogram: each participantprovidedthehighestrating foritem sthatasked T im eP ointsof M easurem ent: how m uchshelikedbeing intheprojectandhow m uch shelearned. O therM easures: R oleplaying: A m aletrainerplayedtheroleof astaff Attendance/T reatm entCom pletion:N otreported personandpresentedaluretotheparticipant. R ole playassessm entswerealwaysconductedfollowing the G 7 this document is a research report submitted to the U. M easures R esults StudyQ uality verbalreportassessm entsbutweredifferentincontent. T im eP ointsof M easurem ent: T hesescenarioswere presentedduring eachbaselineassessm entandpriorto eachtraining session. N aturalisticProbes:priortom eeting withthe participantsinthefirsttraining session, am ale confederateunknowntotheparticipantwasintroduced asanew staff m em ber. W ithin15m inafterbecom ing acquaintedwiththeparticipant, theconfederate presentedoneof theluresfrom thepoolof assessm ent scenarios. T im eP ointsof M easurem ent: T heseprobeswere conductedduring baselineassessm ent, attheconclusion of skillstraining, andagainat1m onthfollowing the conclusionof training. T im eP ointsof M easurem ent:beforeandafter training Q uestionnaireregarding satisfactionwithprogram:readto participants;askedhow m uchtheylikedbeing inthe program, how m uchtheylearnedfrom being inthe program, andwhethertheyweregladtheyhad participated. T im eP ointsof M easurem ent:aftertraining N ote:onem easuregiventostaff abouttheprogram but findingsnotreportedbecausetheydidnotinvolve outcom em easuresof theparticipants G 8 this document is a research report submitted to the U. Com puterbasedsafetyprogram E ducation:N otR eported presentedtosm allgroups;roleplay;pictures;classroom BaselineSam pleSize(andP articipationR ate): discussionand/orteacherchilddiscussion;classroom R ace/E thnicity:N otR eported 50 postersandcoloring sheets;auditoryandsignlanguage used;m ouseandtouchscreen. SexuallyActive:N otR eported P osttestandF ollowup Sam pleSizes(and T heim plem entationof theprogram differedslightly P articipationR ates):N otR eported depending ontheabilityof theparticipants, butingeneral V ictim ization:N otR eported thescenariosweredisplayedonthecom puterscreenwith T im eP ointsof D ataCollection: thesm allgroupsbeforetheparticipantswereofferedthe Crim inalHistory:N otR eported A llparticipantswereassessedbeforetheprogram onlevel opportunitytoworkthroughtheprogram individually of cognitiveabilityandtheknowledgeof personalsafety (withassistance). T woposttestswereconducted1weekand N oneof theschoolshadpreviouslyim plem entedform al 15weeksaftercom pletionof thesafetyprogram Curriculum /Content:(presentedin1998article#71) personalsafetytraining proceduresalthoughteachers M ethods/Setting of D ataCollection: U nderlying conceptsaddressedwithintheprogram were sem istructuredinterviews introducedintwoclassroom basedsessionsdelivered G 9 this document is a research report submitted to the U.

Replication validity of genetic association receptor 2 gene polymorphism Val308Ile and nicotine studies of smoking behavior: what can metaanalytic dependence in genomewide and subsequent associa techniques offerfi Allelic association of the D2 dopamine receptor gene the genetic basis for smoking behavior: a system with receptorbinding characteristics in alcoholism symptoms 1 week after conception purchase levaquin overnight delivery. Stressinduced reinstatement of nicotine in the reinforcing properties of nicotine medications with sulfa discount 750 mg levaquin with amex. Self PlazaZabala A treatment 6th nerve palsy buy cheap levaquin 750mg on-line, Flores A symptoms als buy line levaquin, MartinGarcia E medications used for depression buy discount levaquin 750mg on line, Saravia R hb treatment buy discount levaquin on-line, efficacy modulates the neural correlates of craving in Maldonado R, Berrendero F. Addiction orexin receptor1 in cueinduced reinstatement of nic Biology 2018;23(5):117988. A Nacetylcysteine for therapyresistant tobacco use dis nicotine conjugate vaccine reduces nicotine distribu order: a pilot study. Intermediate phenotypes in acetylcholine receptors both contribute to behaviors psychiatric disorders. Molecular mechanisms underlying macogenetics: role of genetic variation in nicotine behaviors related to nicotine addiction. Biologic approaches to treat substance induced pathophysiology by an adenovirus hexon use disorders. A genetic association for cigarette smoking otinic receptor subunit alters nicotine consumption. Cholinergic nicotinic receptor and heart rate increases from intravenous nicotine. Nicotinic recep cits associated with cocaine and nicotine with tors in the habenulointerpeduncular system are nec drawal and somatic signs of nicotine withdrawal. Tissuedependent effects of immunization olite ratio predicts smoking topography and carcinogen with a nicotine conjugate vaccine on the distribution of biomarker level. Varenicline for smoking cessation: nausea in young adults from the National Longitudinal severity and variation in nicotinic receptor genes. Smoking analyses identify multiple loci associated with smoking abstinenceinduced changes in resting state func behavior. Brief meditation training Tronci V, Vronskaya S, Montgomery N, Mura D, Balfour induces smoking reduction. Nicotine activation of alpha4* receptors: suffi comes in Caucasian smokers despite associations with cient for reward, tolerance, and sensitization. The Thompson J, Thomas N, Singleton A, Piggott M, Lloyd Health Consequences of Smoking: Nicotine Addiction. Department of Health and Human Services, smoking initiation and nicotine dependence. Neurobiologic Behavioral Basis for SmokingAttributable Disease: advances from the brain disease model of addiction. Department Wang C, Shen Z, Huang P, Qian W, Yu X, Sun J, Yu H, Yang of Health and Human Services, Centers for Disease Y, Zhang M. Altered spontaneous activity of posterior Control and Prevention, National Center for Chronic cingulate cortex and superior temporal gyrus are asso Disease Prevention and Health Promotion, Office on ciated with a smoking cessation treatment outcome Smoking and Health, 2012. Sex effects on quittingmotivated cigarette smokers exhibit different smoking cue perception in nonsmokers, smokers, patterns of cueelicited brain activation when antici and exsmokers: a pilot study. Cigarette smoking cessation therapies: a systematic review and smoking leads to persistent and dosedependent metaanalysis. Acetylcholine acts amygdala attenuates stressinduced reinstatement through nicotinic receptors to enhance the firing rate of nicotine seeking in rats. Effectiveness of 41) and the alpha2adrenergic receptor agonist nicotine patches in relation to genotype in women clonidine on stressinduced reinstatement of nico versus men: randomised controlled trial. This chapter primarily reviews the find this chapter also addresses the clinically relevant ben ings published between 2000 and 2017 on disease risks efits of cessation for mitigating the effects of diseases, par from smoking and how these risks change after smoking ticularly in persons with cancer and coronary heart disease. This chapter also reviews cessation and cessation across all phases of reproduction, from precon cardiovascular disease and the implications of cessation for ception to birth, and also for male reproductive health. Methodologic Challenges There are methodologic challenges related to Observational studies should consider factors that assessing smoking cessation and its links to health out might differ between those who quit smoking and those comes in both observational and intervention studies. Some persons may quit smoking Risks in former smokers should be compared with those because they are sick, and healthconscious persons may of current or never smokers, thus necessitating a pre be more motivated to quit. Whenever pos years smoked], which incorporates both smoking inten sible, observational analyses should also adjust for other sity and duration), and changes in smoking status during risk factors that may confound the relationship between followup. Instead, for these sites, this report summarizes new evidence from large pooled analyses or metaanalyses that were deter Biological Mechanisms mined to clarify the consequences of smoking cessation. Collectively, these mechanisms can act at the early and (b) decrease in former smokers with increasing and late stages of carcinogenesis, implying that smoking number of years since cessation. Smoking cessation reduces the risk of lung cancer compared with continued smoking. For example, after 10 years of abstinence, the risk of lung cancer is about 30 to 50 percent of the risk for continuing smokers: with further abstinence, the risk continues to decline. The reduced risk of lung cancer among former smokers is observed in males and females, in smokers of filter and nonfilter cigarettes, and for all histologic types of lung cancer. Smoking cessation lowers the risk of laryngeal cancer compared with continued smoking. Smoking cessation reduces the severity and extent of premalignant histologic changes in the epithelium of the larynx and lung. Smoking cessation halves the risks for cancers of the oral cavity and esophagus, compared with continued smoking, as soon as 5 years after cessation, with further reduction over a longer period of abstinence. Smoking cessation reduces the risk of pancreatic cancer, compared with continued smoking, although this reduction in risk may only be measurable after 10 years of abstinence. Smoking is a cause of bladder cancer; cessation reduces risk by about 50 percent after only a few years, in comparison with continued smoking. The risk of cervical cancer is substantially lower among former smokers in comparison with continuing smokers, even in the first few years after cessation. This finding supports the hypothesis that cigarette smoking is a contributing cause of cervical cancer. Neither smoking nor smoking cessation are associated with the risk of cancer of the breast. For this report, epidemiologic studies of smoking cancer faced by longterm smokers later in life. Chen and colleagues (2016), who carried out a tion grouped by gender and global region. Studies of esophageal squamous cell of data on smoking cessation from 17 casecontrol studies carcinoma have revealed declining risks with increasing (Marron et al. In observed among former smokers with 20 or more years the three largest studies (Hartge et al. Potential biological mechanisms include chronic in nine cohort studies (Chao et al. These studies are sum A metaanalysis of more than 30 studies of cigarette marized in Table 4. In general, risk estimates for the highest category of number of years Taken together, these four studies provide evi since cessation (ranging from >10 years to >20 years) dence that former smokers have somewhat lower risk for were lower than those for categories with fewer numbers colorectal cancer than do current smokers. In ship between cigarette smoking and colorectal cancer most of these studies (Chao et al. Although the excess risk were lower than those for categories with fewer number of of colorectal cancer associated with current smoking years since cessation. Since 2008, four cohort with risk of other subtypes of colorectal cancer (Campbell studies that each included more than 1, 000 incident cases et al. Finally, Shields and colleagues (2004), in a case sation reduced risk of cervical cancer. Biological mechanisms for such a relationship may smoke and suppression of the immune system, including include oxidative stress (Patel et al. As noted data that included information on number of years since previously, results from many studies (Calle et al. The evidence is sufficient to infer that smoking time since smoking cessation, particularly for specific cessation reduces the risk of liver cancer. The evidence is sufficient to infer that smoking incident colorectal cancer and established precursor lesions cessation reduces the risk of cervical cancer. The evidence is sufficient to infer that smoking cessation reduces the risk of kidney cancer. The evidence is sufficient to infer that smoking Conclusions cessation reduces the risk of acute myeloid leukemia. The evidence is sufficient to infer that the relative cessation reduces the risk of lung cancer. The evidence is sufficient to infer that smoking tinuing to smoke, with risk decreasing to half that cessation reduces the risk of laryngeal cancer. The evidence is sufficient to infer that smoking Implications cessation reduces the risk of esophageal cancer. The evidence is sufficient to infer that smoking risk has long been an important part of the rationale for cessation reduces the risk of pancreatic cancer. The evidence is sufficient to infer that smoking tiatives to make evidencebased, barrierfree cessation cessation reduces the risk of bladder cancer. The evidence is sufficient to infer that smoking reduces the risk of several additional types of cancer fur cessation reduces the risk of stomach cancer. The evidence is sufficient to infer that smoking important role that smoking cessation plays in cancer cessation reduces the risk of colorectal cancer. Smoking Cessation After a Cancer Diagnosis this section reviews evidence of the health benefits disease progression or recurrence, cancerspecific mor of smoking cessation at the time of a cancer diagnosis or tality, second primary cancer, quality of life, or treatment after that diagnosis compared with continuing to smoke. Among longterm cancer survivors, Previous reports of the Surgeon General have not the smoking prevalence is approximately 9% (Warren evaluated the health benefits of smoking cessation after and Simmons 2018). The 2014 report with diagnosis (referred to as persistent smokers), and was also the first to conclude that continued smoking quitters. The cohorts were composed of patients with after a cancer diagnosis causes adverse health outcomes lung cancer (four studies), with head/neck cancer (three among cancer patients or survivors. In all three studies, continued smoking after a of the evidence on smoking cessation after a cancer diag cancer diagnosis significantly increased risk of mortality nosis is important. In all four studies, continued smoking was associated with increased allcause mortality rela They had a baseline and final cohort size of at least tive to quitting.

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