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If positive insomnia quotes for facebook buy meloset 3 mg, check viral load and consult with cKi-67 proliferation fraction of <30% in lymph nodes is associated with a more gastroenterologist sleep aid snoring discount meloset 3 mg visa. High rate of durable remissions after treatment of randomised sleep aid vs sleeping pills purchase 3mg meloset free shipping, phase 3 non-inferiority trial sleep aid brands cheap meloset 3mg free shipping. Open-label, randomized, noninferiority study of bendamustinewith rituximab plus high-dose methotrexate and cytarabine. Bendamustine plus rituximab versus fudarabine plus rituximab multicentre trial from Gruppo Italiano Studio Linfomi. Long-term progression-free survival of mantle cell Robak T, Huang H, Jin J, et al. N lymphoma following intensive front-line immunochemotherapy with in vivo-purged stem cell Engl J Med 2015;372:944-953. J Clin Oncol 2005;23:1984by high dose therapy with autologous stem cell transplantation induces higher rates of molecular 1992. Rituximab after autologous stem-cell transplantation Lenalidomide + rituximab in mantle-cell lymphoma. Blood in patients with mantle cell lymphoma, a subgroup analysis of the LyMa trial [abstract]. Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation. Bortezomib in patients with relapsed or refractory mantle cell Dreyling M, Lenz G, Hoster E, et al. Ann Oncol by autologous stem cell transplantation in first remission significantly prolongs progression-free survival 2009;20:520-525. Chemotherapy with rituximab followed by high-dose Ibrutinib therapy and autologous stem cell transplantation in patients with mantle cell lymphoma. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Ibrutinib, lenalidomide, rituximab Rituximab maintenance Jerkeman M, Hutchings M, Raty R, et al. Maintenance rituximab after autologous stem cell Lenalidomide transplantation in patients with mantle cell lymphoma. Lenalidomide oral monotherapy produces a high response Le Gouill S, Thieblemont C, Oberic L, et al. Rituximab after autologous stem-cell transplantation in rate in patients with relapsed or refractory mantle cell lymphoma. Single-agent lenalidomide in patients with mantle-cell lymphoma who Elderly Trial. Second-line Therapy Lenalidomide + rituximab Acalabrutinib Wang M, Fayad L, Wagner-Bartak N, et al. Lenalidomide in combination with rituximab for patients with Wang M, Rule S, Zinzani P, et al. Efficacy and safety of acalabrutinib monotherapy in patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial. Bendamustine plus rituximab is effective and has a favorable relapsed or refractory non-Hodgkin lymphoma. The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma. Performance status fi2 1 aThe International Non-Hodgkin’s Lymphoma Prognostic Factors Project. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma. Gray zone lymphoma with features intermediate between classical Hodgkin lymphoma and diffuse large B-cell lymphoma: Characteristics, outcomes, and prognostication among a large multicenter cohort. Chemotherapy with or without radiotherapy in limited-stage difuse Zaja F, Tomadini V, Zaccaria A, et al. Bendamustine is efective in relapsed or refractory Lopez A, Gutierrez A, Palacios A, et al. Bendamustine combined with rituximab for patients with Corazzelli G, Capobianco G, Arcamone M, et al. Long-term results of gemcitabine plus oxaliplatin with relapsed or refractory difuse large B cell lymphoma. Efective salvage therapy for lymphoma with Xiros N, Economopoulos T, Valsami S, et al. Blood 1988;71:117chemotherapy in patients with primary refractory or early relapsed T cell rich B cell lymphoma. Efcacy and safety of gemcitabine, carboplatin, Wang M, Fowler N, Wagner-Bartak N, et al. Serious events may include atrial fbrillation and ventricular tachycardia, cardiac arrest, cardiac failure, renal insufciency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome. The most common neurologic toxicities included encephalopathy, headache, tremor, dizziness, aphasia, delirium, insomnia, and anxiety. Serious events including leukoencephalopathy and seizures occurred with axicabtagene ciloleucel. Fatal and serious cases of cerebral edema have occurred in patients treated with axicabtagene ciloleucel. Grade 2 Administer tocilizumab 8 mg/kg intravenously over 1 hour (not Manage per Grade 3 if no Symptoms require and respond to moderate to exceed 800 mg). Repeat tocilizumab every 8 hours as needed if not responsive Oxygen requirement <40% FiO2 or hypotension to intravenous fuids or increasing supplemental oxygen. Grade 3 Per Grade 2 Administer methylprednisolone 1 Symptoms require and respond to aggressive mg/kg intravenously twice daily or intervention. Oxygen requirement fi40% FiO2 or hypotension requiring high-dose or multiple vasopressors or Continue corticosteroid use until the Grade 3 organ toxicity or Grade 4 transaminitis. Moderate symptoms: limiting If no improvement within 24 hours after starting tocilizumab, Continue dexamethasone use until the event is Grade 1 or less, instrumental activities of daily administer dexamethasone 10 mg intravenously every 6 hours if not then taper over 3 days. Continue dexamethasone use until the event is Grade 1 or less, then taper over 3 days. Administer methylprednisolone 1000 mg intravenously per day Life-threatening Administer methylprednisolone 1000 mg intravenously per day with for 3 days; if improvement is seen, then manage as above. Consider non-sedating, anti-seizure medicines (eg, levetiracetam) for seizure prophylaxis. Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysis. Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Optimum management of this rare subtype is undefined, though it is with expertise in the management of the disease. Tests include hepatitis B surface antigen and dSee Use of Immunophenotyping/Genetic Testing in Differential Diagnosis of Mature core antibody for a patient with no risk factors. Tests include hepatitis B surface antigen and core antibody for a patient with no risk factors. In general, avoidance of zidovudine, cobicistat, and ritonavir is strongly recommended. Highly efective treatment of acquired immunodefciency for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Tests include hepatitis B surface antigen and centers with expertise in the management of the disease. Consider baseline imaging and direct visualization to screen for rituximab used in combination with ibritumomab tiuxetan. Avoid “shotgun” panels of unnecessary antibodies unless a clinically urgent situation warrants. Interpretation of results should be based on individual circumstances and may vary. Interpretation of results should be based on Small/medium/large cells individual circumstances and may vary.

The National Childhood Vaccine Injury Act Reporting and Compensation Table has been restructured to 3z sleep aid order cheap meloset on line include adverse events and intervals from vaccination to insomnia 36 hours buy meloset 3 mg without a prescription onset of event for reporting and for compensation sleep aid 25mg uk order discount meloset on-line. The table of Nationally Notifable Infectious Diseases in the United States has been updated to sleep aid guidelines buy meloset 3 mg include diseases notifable in 2012. To accomplish these goals, physicians must make timely immunization, including active and passive immunoprophylaxis, a high priority in the care of infants, children, adolescents, and adults. The global eradication of smallpox in 1977, elimination of poliomyelitis disease from the Americas in 1991, elimination of ongoing measles transmission in the United States in 2000 and in the Americas in 2002, and elimination of rubella and congenital rubella syndrome from the United States in 2004 serve as models for fulflling the promise of disease control through immunization. These accomplishments were achieved by combining a comprehensive immunization program providing consistent, high levels of vaccine coverage with intensive surveillance and effective public health disease control measures. Future success in the worldwide elimination of polio, measles, rubella, and hepatitis B is possible through implementation of similar prevention strategies. High immunization rates, in general, have reduced dramatically the incidence of all vaccine-preventable diseases (see Tables 1. Yet, because organisms that cause vaccine-preventable diseases persist in the United States and elsewhere around the world, continued immunization efforts must be maintained and strengthened. Discoveries in immunology, molecular biology, and medical genetics have resulted in burgeoning vaccine research. Licensing of new, improved, and safer vaccines; anticipated arrival of additional combination vaccines; establishment of an adolescent immunization platform; and application of novel vaccine-delivery systems promise a new era of preventive medicine. The advent of population-based postlicensure studies of new vaccines facilitates detection of rare adverse events temporally associated with immunization that were undetected during prelicensure clinical trials. Identifcation of the rare occurrence of intussusception after administration of the frst licensed oral rhesus rotavirus vaccine confrmed the value of such surveillance systems. Physicians must regularly update their knowledge about specifc vaccines, including information about their recommended use, safety, and effectiveness. Each edition of the Red Book provides recommendations for immunization of infants, children, and adolescents. Whereas immunization recommendations represent the best approach to disease prevention on a population basis, in rare circumstances, individual considerations may warrant a different approach. Comparison of 20th Century Annual Morbidity and Current Morbidity: Vaccine-Preventable Diseasesa 20th Century 2010 Reported Percent Disease Annual Morbidityb Casesc Decrease Smallpox 29 005 0 100 Diphtheria 21 053 0 100 Measles 530 217 63 >99 Mumps 162 344 2612 98 Pertussis 200 752 27 550 86 Polio (paralytic) 16 316 0 100 Rubella 47 745 5 >99 Congenital rubella syndrome 152 0 100 Tetanus 580 26 96 Haemophilus infuenzae 20 000 246d 99 a National Center for Immunization and Respiratory Diseases. Comparison of Prevaccine Era Estimated Annual Morbidity With Current Estimates: Vaccine-Preventable Diseasesa Prevaccine Era 2010 Reported Disease Annual Estimate Cases Percent Decrease Hepatitis A 117 333b 9670c 92 Hepatitis B (acute) 66 232b 3374c 95 Pneumococcus (invasive) All ages 63 067b 16 569c 84 <5 years of age 16 069b 1877c 88 Rotavirus (hospitalizations, 62 500d 28 125e 55 <3 years of age) Varicella 4 085 120b 9920c 99. Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States. Sources of Vaccine Information In addition to the Red Book, which is published every 3 years, physicians should use evidence-based literature and other sources for data to answer specifc vaccine questions encountered in practice. Each product insert lists contents of the vaccine, including preservatives, stabilizers, antimicrobial agents, adjuvants, and suspending fuids. Health care professionals should be familiar with the label for each product they administer. Most manufacturers maintain Web sites with current information concerning new vaccine releases and changes in labeling. Additionally, 24-hour contact telephone numbers for medical questions are available in the Physicians’ Desk Reference ( The monograph also provides information about other vaccines recommended for travel in specifc areas and other information for travelers. For additional sources of information on international travel, see International Travel (p 103). Annual course offerings include the Immunization Update, Vaccines for International Travel, Infuenza, and a 9-module introductory course on the Epidemiology and Prevention of Vaccine-Preventable Diseases. The course schedule, slide sets, and written materials can be accessed online ( This system responds to immunization-related questions submitted from health care professionals and members of the public. The hotline is a telephone-based resource available to answer immunization-related questions from health care professionals and members of the public. Appendix I (p 883) provides a list of reliable immunization information resources, including facts concerning vaccine effcacy, clinical applications, schedules, and unbiased information about safety. Two resources comprehensively address concerns of practicing physicians: the National Network for Immunization Information ( Information can be obtained from state and local health departments about current epidemiology of diseases; immunization recommendations; legal requirements; public health policies; and nursery school, child care, and school health concerns or requirements. Information regarding global health matters can be obtained from the World Health Organization ( Online catch-up immunization schedulers are available for use by parents, other care providers, and health care professionals. The schedulers are based on the recommended immunization schedules for children, adolescents, and adults. The schedulers, which can be downloaded, allow the user to determine vaccines needed by age and are useful for viewing missed or skipped vaccines quickly according to the recommended childhood and adult immunization schedules. The inter active vaccine schedules are available at the following sites: catch-up scheduler. Questions should be encouraged, and adequate time should be allowed so that information is understood ( This applies in all settings, including clinics, offces, hospitals (eg, for the birth dose of hepatitis B vaccine), and pharmacies. Health care professionals also should be aware of local confdentiality laws involving adolescents. Health care professionals should be familiar with requirements of the state in which they practice. Parental Concerns About Immunization Health care professionals should anticipate that some parents will question the need for or the safety of immunizations, want to space out vaccines, refuse certain vaccines, or even decide to reject all immunizations for their child. Some parents may have religious or philosophic objections to immunization, which are permitted by some states. Several factors contribute to parental vaccine concerns or lack of understanding of the benefts of vaccines, including: (1) lack of information about the vaccine being given and about immunizations in general; (2) opposing information from other sources (eg, alternative medicine practitioners, antivaccination organizations, some religious groups, and alternative Web sites); (3) mistrust of the source of information (eg, vaccine manufacturer); (4) perceived risk of serious vaccine adverse events; (5) concern regarding number of injections or the vaccine schedule; (6) information being delivered in a way that does not recognize cultural differences or that is not tailored to individual concern; (7) information being delivered at an inconvenient time; (8) not perceiving risk of vaccines accurately; and (9) lack of appreciation of the severity of vaccine-preventable diseases. One important aspect physicians can control is their relationship with patients and their parents. If parents trust their child’s physician, information presented to them by the physician in support of vaccines is accepted more readily. A nonjudgmental approach is best for parents who question the need for immunizations. Ideally, health care professionals should determine in general terms what parents understand about vaccines their children will be receiving, the nature of their concerns, their health beliefs, and what information they fnd credible. People understand and react to vaccine information on the basis of a variety of factors, including previous experiences, attitudes, health beliefs, personal values, and education. The method in which data are presented about immunizations as well as a person’s perceptions of the risks of disease, perceived ability to control those risks, and risk preference also contribute to understanding of immunizations. For some people, the risk of immunization can be viewed as disproportionately greater than the risk of disease so that immunization is not perceived as benefcial, in part because of the relative infrequency of vaccine-preventable diseases in the United States. Others can dwell on sociopolitical issues, such as mandatory immunization, informed consent, and the primacy of individual rights over that of societal beneft. Parents may be aware through the media or information from alternative Web sites about alleged controversial issues concerning vaccines their child is scheduled to receive. When a parent initiates discussion about an alleged vaccine controversy, the health care professional should listen carefully and then calmly and nonjudgmentally discuss specifc concerns. Health care professionals always should provide factual information and use language appropriate for parents and other care providers. Through direct dialogue with parents and use of available resources, health care professionals can help reduce and possibly prevent acceptance of inaccurate media reports and information from nonauthoritative sources. Encouraging a dialogue may be the most important step to eventual vaccine acceptance. Helpful information sources that can be provided to parents or to which parents can be directed include the National Center for Immunization and Respiratory Diseases’ “Parent’s Guide to Childhood Immunization” ( Parents who refuse vaccines should be advised of state laws pertaining to school or child care entry, which can require that unimmunized children not attend school during disease outbreaks. Documentation of such discussions in the patient’s record may help to decrease any potential liability should a vaccine-preventable disease occur in an unimmunized patient. This informed refusal documentation should note that the parent was informed why the immunization was recommended, the risks and benefts of immunization, and the possible consequences of not allowing the vaccine to be administered. Parental Refusal of Immunization the approach of a health care professional to a parent who refuses immunization of his or her child is complex and should be based on the reason for refusal and knowledge of the parent.

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In a series of 94 patients (74 of whom were followed for approximately 1 year or more) insomnia symptoms order meloset now, these authors reported an average elevation of pitch from 139 Hz preoperatively to sleep aid equipment cheap 3 mg meloset visa 196 Hz postoperatively insomnia 1cd10 buy meloset visa. In addition sleep aid non prescription 3 mg meloset sale, while the surgery is generally well tolerated, it does place the airway at risk and require an external incision in the anterior neck skin. Surgeries to increase tension by producing scar on the vocal folds As previously mentioned, vocal fold vibration rate, which determines the pitch of the voice, is affected by vocal fold mass (as the mass decreases, the vibration rate or pitch increases) and tension (as the tension increases the vibration and pitch increases). This has led surgeons to attempt to elevate pitch by increasing tension through scarring the surface of the vocal folds or scarring the front portion of the vocal folds together to shorten the portion available for vibration. The main advantage of these types of procedures is that they can be done through June 17, 2016 165 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People the mouth without an incision in the neck, are well tolerated, and do no place the patient’s breathing at significant risk. The main disadvantage is that healing and scar production can be unpredictable and results variable. Variations on this procedure have replicated results in multiple small patient series from other centers. In all patients, there is a modest increase in degree of vocal roughness postoperatively, and this is more noticeable when the procedure is performed in patients over 50 years of age. The procedure can also be repeated if healing does not result in as much scar as desired, and can be performed in patients who have failed other types of surgery. Voice masculinization Far fewer transgender males present for voice evaluation and treatment than transgender females. This may be related to the reduction in pitch that transgender males experience as a result of hormone therapy. Following response to this treatment, it is reported that about 75% of trans men are identified as male by telephone. The perceived masculinity of voice is related not only to pitch but also to the proximity of the habitual speaking pitch to the pitch floor, or lowest pitch. These changes in resonance are further supported by data showing a change in formant frequencies June 17, 2016 166 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People (the acoustic correlate of resonance) during the first year of hormone treatment in conjunction with behavioral intervention. However, transgender women who were misidentified as male had fewer upward and more downward intonation patterns than females and transgender females who were correctly identified. However, if increasing breathiness [9,17] and using lower vocal intensity [13,17] contributes to voice feminization, it may be considered that reducing breathiness and avoiding a soft voice may be perceived as more masculine. Behavioral intervention While pitch is primarily addressed through hormone therapy and secondarily by voice therapy, the other components of voice production are primarily addressed through behavioral voice therapy. Flow phonation and resonant voice therapy are two common voice therapy techniques. Flow phonation targets the balanced exhalation of airflow during voice production using respiration as the power source to achieve vocal efficiency. Resonant voice therapy focuses on achieving easy phonation while experiencing the energy or vibration of sound in the oral cavity. Some transmasculine spectrum people seek only some voice masculinization, and desire flexibility with their voice and communication. With this in mind, voice therapy should be patient specific and physiologically based to achieve patient and therapy goals in a vocally efficient and safe manner. Effects of testosterone hormone therapy on voice 90% of trans men will achieve acceptable voice results, lowering of pitch into a gender neutral or male range, after 4 to 5 months of taking exogenous androgens. Surgical consideration As hormonal therapies and behavioral therapies are effective in helping 90% of transgender men achieve acceptable voice, surgical intervention is rarely indicated in this group. If needed, however, relaxation thyroplasty, designed to reduce the tension of the vocal folds can be performed. This same surgery is used in male patients with inappropriately elevated pitch and results in a reduction of pitch if performed in the original method [45] and an even greater reduction if modified as described by other authors. Typical pitch reduction is in the range of 100 Hz and usually results in the patient attaining an acceptable male vocal pitch. However, as the vocal cord tension is less controllable after the intervention, the voice is often perceived as more rough and with less volume. Working with the transgender voice: the role of the speech and language therapist. The effectiveness of oral resonance therapy on the perception of femininity of voice in male-to-female transsexuals. Voice and communication change for gender nonconforming individuals: Giving Voice to the Person Inside. Self-perceptions of pragmatic communication abilities in male-to-female transsexuals. Development and preliminary evaluation of the transsexual voice questionnaire for male-to-female transsexuals. June 17, 2016 168 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People 10. Voice parameters that result in identification or misidentification of biological gender in male-to-female transgender veterans. Voice and communication therapy for the transgender/transsexual client: a comprehensive clinical guide. Wendler glottoplasty and voice-therapy in male-to-female transsexuals: results in pre and post-surgery assessment. Phonetograms, aerodynamic measurements, self-evaluations, and auditory perceptual ratings of male-to-female transsexual voice. Comparison of acoustic and perceptual measures of voice in male-to-female transsexuals perceived as female versus those perceived as male. Transgender voice and communication treatment: a retrospective chart review of 25 cases. Transgender voice and communication: research evidence underpinning voice intervention for male-to-female transsexual women. A preliminary study on the use of vocal function exercises to improve voice in male-to-female transgender clients. Perceptual and acoustic outcomes of voice therapy for male-tofemale transgender individuals immediately after therapy and 15 months later. June 17, 2016 169 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People 22. Pitch elevation in trangendered patients: anterior glottic web formation assisted by temporary injection augmentation. Thyroid cartilage and vocal fold reduction: a new phonosurgical method for male-to-female transsexuals. Wendler glottoplasty: an effective pitch raising surgery in male-to-female transsexuals. June 17, 2016 170 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People 37. Long-term outcome of endoscopic shortening and stiffening of the vocal folds to raise the pitch. Transmasculine people’s vocal situations: a critical review of gender-related discourses and empirical data. Evaluation of a consecutive group of transsexual individuals referred for vocal intervention in the west of Sweden. Endocrine therapy for transgender adults in British Columbia: suggested guidelines. June 17, 2016 171 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People 35. Health insurance coverage issues for transgender people in the United States Primary authors: Andre A. The burden of fighting against this level of adversity when people are physically ill or injured represents a significant barrier to care. This adversity has contributed to the high incidence of transgender people avoiding seeking needed health care. These are “health benefits plans” and are not “insurance plans” strictly speaking, although they may appear the same to the enrolled member. Most carriers have now issued their own internal guidelines specific to transgender-related healthcare, especially surgical interventions. These guidelines (called by various names such as medical policies or coverage positions) spell out what services will be covered for a specific medical condition June 17, 2016 172 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People and usually apply to all insurance products issued by a carrier. Thus, what is covered by a given health plan will vary not only by state but also by employer.

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All-cause as well as cardiovascularand cerebrovascular-specific mortality among transgender men did not differ from the general Dutch population sleep aid exchange select purchase meloset 3 mg with mastercard. Direct study of the effects of hormones on lipids and blood pressure in transgender people has been limited insomnia 6 days after ovulation purchase 3mg meloset with amex. A retrospective study of lipids in 169 Austrian transgender people found trends of poorer lipid profiles in both transgender women and men at 5 years however these changes were mild at most insomnia reasons order meloset 3 mg with visa, and seemed to insomnia young living oils purchase genuine meloset be mitigated to some degree by the use of transdermal estradiol. Currently there is no guidance on whether to use risk calculators based on natal sex or affirmed gender. It may be reasonable to use natal sex-based calculators in transgender people who have transitioned later in life, given their long-term exposure to the natal hormonal milieu. However with an increasing percentage of transgender people beginning hormone therapy in adolescence and young adulthood, affirmed gender-based calculators may be more appropriate in these cases. Ultimately a primary goal is to calculate a realistic risk-benefit ratio between the benefits of statin therapy or aspirin and the risks of these treatments. Depending on the age at which hormones are begun and total length of exposure, providers may choose to use the risk calculator for the natal sex, affirmed gender, or an average of the two (Grading: X C M). Another goal of calculating risk is to provide adequate information during the informed consent process to allow transgender people of any age, and with or without existing cardiovascular or cerebrovascular disease, to make informed decisions about the long term implications of gender-affirming hormones. It is theoretically possible that the psychosocial benefits of hormone therapy may June 17, 2016 73 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People have an independent and protective effect through reduction of stress, improved body image resulting in healthier lifestyle choices, reduced tobacco use, and increased physical activity. Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern. An analysis of all applications for sex reassignment surgery in Sweden, 1960-2010: prevalence, incidence, and regrets. June 17, 2016 74 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People 11. Effect of sex steroid use on cardiovascular risk in transsexual individuals: a systematic review and meta-analyses. Cross-sex hormone therapy alters the serum lipid profile: a retrospective cohort study in 169 transsexuals. Effects of oral and transdermal estrogen replacement therapy on markers of coagulation, fibrinolysis, inflammation and serum lipids and lipoproteins in postmenopausal women. June 17, 2016 75 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People 12. The effect of gender-affirming hormone therapy on diabetes risk or disease course is unclear. A Dutch case-control study noted an increased prevalence of type 2 diabetes mellitus among transgender men and women in comparison to both age matched non-transgender male and female groups, however the study did not adjust for other risk factors. While insulin resistance serves as a useful surrogate marker to inform risk, outcome studies using a diagnosis of diabetes as the end point have not been conducted. Otherwise young and healthy transgender people will often seek medical care with the sole purpose of obtaining hormone therapy or surgery. This can be viewed as an opportunity to improve health particularly in transgender women, who may be at increased cardiovascular risk. However, caution should be used to avoid making gender-affirming care contingent on tight control of these other conditions. Numerous anecdotes exist of poorly controlled diabetic transgender patients who had improvements in self-care and resultant decline in hemoglobin A1c after initiation of gender-affirming hormones. Testosterone package inserts recommend monitoring as serum glucose may be lowered in patients with diabetes receiving testosterone. It is reasonable to maintain heightened monitoring of indicators such as fasting glucose and hemoglobin A1c when initiating or adjusting hormone therapy. Patients with diabetes seeking gender-affirming surgeries represent a special group for whom aggressive treatment to normalize glucose control is desirable. Healing, avoidance of infection, June 17, 2016 76 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People functionality and cosmesis are thought to be improved with better glycemic control. While the presence of diabetes in itself may not be a contraindication for any of these surgeries, careful coordination between the surgeon and the provider managing the diabetes is recommended. Prevalence of cardiovascular disease and cancer during cross-sex hormone therapy in a large cohort of trans persons: a case-control study. Effects of sex steroids on components of the insulin resistance syndrome in transsexual subjects. Effects of testosterone on Type 2 diabetes and components of the metabolic syndrome. Distinctive features of female-to-male transsexualism and prevalence of gender identity disorder in Japan. Management of medical morbidities and risk factors before surgery: smoking, diabetes, and other complicating factors. June 17, 2016 77 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People 13. Osteoporosis screening is currently ageand sexbased, and also individualized on the basis of risk factors. There are a number of lifestyle, genetic, endocrinologic, hematologic, rheumatoid and autoimmune diseases, as well as medications that contribute to osteoporosis. Known risk factors for osteoporosis include underutilization of hormones after gonadectomy or use of androgen blockers without or with insufficient estrogen. Osteoporosis risk in transgender men Most published studies to date have shown either no change, or an increase in bone mineral density in transgender men treated with testosterone. Risk factors for osteoporosis in this population include oophorectomy before age 45 without optimal hormone replacement. Screening intervals in transgender people can be based on these recommendations as well. All professional organizations recommend screening for all non-transgender women over age 65. Some older guidelines recommend screening in non-transgender men after age 70 or in those with risk factors, while others and more recent guidelines make no recommendations for men. Recommended screening for transgender women and men There is insufficient evidence to guide recommendations for bone density testing in transgender women or men. Transgender people (regardless of birth-assigned sex) should begin bone density screening at age 65. Screening between ages 50 and 64 should be considered for those with established risk factors for osteoporosis. Transgender people (regardless of birth assigned sex) who have undergone gonadectomy and have a history of at least 5 years without hormone replacement should also be considered for bone density testing, regardless of age (Grading: X C W). Special considerations There have been no studies to determine whether clinicians should use the natal sex or affirmed gender for assessment of osteoporosis. Although some researchers use the natal sex, with the assumption that bone mass has usually peaked for transgender people who initiate hormones in early adulthood, this should be assessed on a case by case basis until there is more data available. This assumption will be further complicated by the increasing prevalence of transgender people who undergo hormonal transition at a pubertal age, or soon after puberty. Sex for comparison within risk assessment tools may be based on the age at which hormones were initiated, and length of exposure to hormones. In some cases it may be reasonable to assess risk using both the male and female calculators and using an intermediate value. Weak evidence suggests that agonadal states contribute to an increased risk of osteoporosis, however long term studies are lacking. Advice should be given to modify risk factors for osteoporosis, including tobacco cessation, Correct low vitamin D levels, maintain calcium intake in line with current guidelines for nontransgender people, weight bearing activity, and moderation of alcohol consumption. June 17, 2016 79 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People References 1. Low bone mass is prevalent in male-to-female transsexual persons before the start of crosssex hormonal therapy and gonadectomy. Body composition, volumetric and areal bone parameters in male-to-female transsexual persons. Cortical and trabecular bone mineral density in transsexuals after long-term cross-sex hormonal treatment: a crosssectional study. Reutrakul S, Ongphiphadhanakul B, Piaseu N, Krittiyawong S, Chanprasertyothin S, Bunnag P, et al.

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