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Management of endometriosis rectovaginal endometriosis with an estrogen-progestogen with oral medroxyprogesterone acetate menopause complications buy premarin overnight delivery. Can we decrease breakthrough bleeding in patients with Endometriosis: pathogenesis and treatment menopause age cheap premarin 0.625 mg online. Some women have relatively minimal disease but severe pain symptoms and others are found incidentally with severe anatomical disease but minimal pain menstruation headache causes trusted premarin 0.625mg. One strategy is to pregnancy implantation 0.625mg premarin with mastercard begin the interview with open questioning and then follow with targeted questions. One of the goals of a complete history is to identify patients Physician assessed symptoms however may introduce at risk of having endometriosis. This reduces diagnostic delay bias and therefore standardized questionnaires such as the and provides early detection and treatment of the disease. These standardized Yet the effcacy and accuracy of anamnesis or a detailed scoring systems also provide an unbiased tool for assessing analysis of pain symptoms by standardized questionnaires are improvement in symptoms after any given intervention and limited when it comes to predicting the location and severity for researching new interventions. Monika Martina Wolfer symptoms as determined by standardized questionnaires Universitatsklinik fur Frauenheilkunde und Geburtshilfe are of limited value as to the severity of disease in general, a Landeskrankenhaus Universitatsklinikum Graz differentiated analysis of the mentioned symptoms may still Auenbrugger Platz 14 be very valuable in concrete situations. For instance, there 8036 Graz, Austria is evidence that severe pain in patients with sonographic E-mail: monika. These patients Descriptions of the symptoms of endometriosis by patients require the input of specialists in chronic pain modifcation. Secondary dysmenorrhea requiring analgesia is highly indicative of the presence of endometriosis, adenomyosis of Female sexual distress and sexual dysfunction are frequently the uterus, or both. Especially in a low prevalence population, observed in endometriosis patients, correlated with pain when no other symptoms but cyclical pelvic pain are reported, intensity during or after sexual intercourse. Often the results the evaluation of this symptom can be very useful in detecting are fewer episodes of sexual intercourse per month, greater endometriosis and consecutively referring the patient to feelings of guilt toward the partner, and lowered feelings of laparoscopic diagnosis and therapy at an early stage. Moreover, in this multicenter cohort study almost two-thirds of women agreed that the primary motivation for Review data on adolescent girls with severe dysmenorrhea and sexual intercourse was to conceive, and nearly half stated that chronic pelvic pain revealed that two thirds of these adolescents satisfying the partner was the primary motivation for sexual had laparoscopic evidence of endometriosis; one third of these 20,32 contact. Moreover, a case series of adolescent endometriosis patients demonstrated It is essential to address this topic openly during the interview that severe secondary dysmenorrhea, menorrhagia, and since patients might not bring up dyspareunia or sexual gastrointestinal symptoms during menstruation were the most dysfunction by themselves. There was no Endometriosis affects a signifcant proportion of reproductive signifcant difference whether peritoneum, ovaries, or both age women. Moreover, secondary infertility with endometriosis, but a causal no marked difference emerged between the severity of relationship has yet to be resolved. Thus, in women who wish dysmenorrhea and the site and stage of endometriosis; only to conceive, and have minimal or mild endometriosis, there is women with ovarian endometriosis had lower scores. In women with endometriomas who Thus, dysmenorrhea is a key symptom in adenomyosis as wish to conceive spontaneously, excision of the endometrioma well as it is in the diagnosis of endometriosis. They are Inspection and palpation of the abdomen not necessarily the result of actual involvement of the digestive Physical examination of the pelvis including tract by endometriosis itself, because they frequently occur – Inspection and visualization of the posterior vaginal in women free of nodules in the rectum or other intestinal fornix sites. Therefore, specifc diagnostics for in the pre-operative work-up are standard procedures for the detection of rectal endometriosis are essential. Inspection and palpation of studied population, only one-quarter of women with rectal the abdomen, as well as of scars from previous surgery if endometriosis actually had rectal stenosis. The patient reported signifcantly more often about constipation, should be motivated to indicate the precise location of painful defecation pain, appetite disorders, longer evacuation time, sensations. During inspection of the vagina and cervix in and increased stool consistency without laxatives. Dysuria associated with menstruation, and cyclic hematuria In such cases, rectal palpation can be helpful for the diagnosis are suggestive of endometriotic involvement of the bladder 7 of endometriosis. Excision of bladder endometriosis is relatively straightforward for When there is suspicion of endometriosis, special attention experienced practitioners and often relieves symptoms should be paid to the examination of adnexal masses, completely. Referral to endometriosis centres is recommended painful induration, and/or nodules of the rectovaginal wall, if bladder endometriosis is suspected. Progression of this stenosis physical examination alone might be limited because it cannot often goes unnoticed as symptoms are rare and it can lead to be reproduced and depends on the clinician’s skills. The combination of physical examination and might report symptoms of a vasovagal reaction like syncope, transvaginal ultrasound, however, allows accurate prediction nausea, or sometimes even vomiting. The evidence that these of endometriosis affecting the ovaries, vagina, rectum, symptoms are associated with the presence or severity of uterosacral ligaments, rectovaginal space, and pouch of Douglas. Ovarian disease and moderate or severe disease can be accurately predicted with the correct technique 2. An accurate non-invasive diagnosis of the stage of disease is helpful as: there is signifcant overlap of symptoms with other diseases such as adenomyosis; patients may choose fertility treatment prior to surgery; when surgery is chosen it enables 2. The authors with ureteric laparoscopic ureterolysis and/or stenting helps suggest that this scoring system might facilitate triage of to prevent any loss of renal function. The ovary was deemed to be completely free when all of its borders could be seen sliding It is useful to always follow the same routine when assessing across the surrounding structures. Patients should be examined in present when they can not be separated from surrounding the dorsolithotomy position and the free hand should be used structures. Ultrasound has the advantage of being a dynamic technique and this movement of organs, either by gentle pressure with the ultrasound probe or from above with the free hand will elicit free movement of organs against one another when no adhesions exist. First the endometrial cavity should be assessed both for anomalies and for any pathology. It is helpful to ask the patient to empty their bladder before the history is taken so that there is a small amount of urine. The bladder should be easily separated from the uterus by gentle pressure between the bladder and uterus with the probe. Adhesions in this area can be from scarring secondary to caesarean section but also from endometriosis. If the bladder wall is thickened at the point where it is stuck to the uterus Fig. Next contents, the cyst located within the centre of the ovary and loss of the ureteric orifce in the bladder can be identifed as a raised ovarian capsule at the point of adherence. In particular, diagnosis of endometrioma, ovarian adhesions, and pouch of Douglas obliteration was shown to be highly accurate. There is a signifcant correlation of histologic diagnosis of adenomyosis and certain ultrasound features, which are Fig. The presence of adhesions in the pouch of Douglas was assessed the presence of adenomyosis signifcantly reduces the by evaluating the uterus. A combination of pressure on the likelihood of pregnancy in women trying to conceive. It is also the bowel behind and the posterior uterine serosa in front is associated with an increased risk of early pregnancy loss. If these two surfaces were completely free of prior to medically assisted reproductive procedures and one another, then adhesions were assumed to be unlikely. If adhesions are present then further evaluation of the posterior structures (such as the rectal muscularis, uterosacral 2. False positive results well-trained professionals following a complete history that are rare, however, negative fndings are less reliable, and accounts for the patient’s needs and potential indications for women with signifcant symptoms may still beneft from further an operation. Uterine sliding sign: a simple sonographic predictor Findings from a national case-control study – Part 1. Diagnostic delay for endometriosis in Austria and sonography, and magnetic resonance imaging to diagnose Germany: causes and possible consequences. Systematic review of endometriosis pain assessment: sonography and clinical examination for preoperative diagnosis how to choose a scale Performance of an Ultrasound Based Endometriosis and distress in patients with endometriosis. Should a detailed ultrasound examination of severity of pelvic endometriosis using transvaginal ultrasound. National German Guideline (S2k): pelvic endometriosis specifc to lesion localizations A preliminary Guideline for the Diagnosis and Treatment of Endometriosis: Long prospective study. Pain typology and incident moving toward a problem-oriented and patient-centered approach.

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  • Repeated injury or usage (such as from typing, playing the piano, or heavy use of hand tools)
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  • May be raised sores (lesions) filled with clear fluid or pus
  • Angina or chest pain
  • Seeds
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They committed money and in-kind aid in various ways breast cancer tattoo design cheap 0.625 mg premarin amex, both individually and collectively menopause facts order premarin 0.625 mg otc. A “public health emergency of international concern” calls upon the reaction of the world’s major economies in at least two ways breast cancer kds premarin 0.625 mg cheap. On the one hand womens health virginia purchase premarin paypal, these countries provide development aid to developing countries on a permanent basis, and are connected by multiple trade, financial and other links. It goes beyond the scope of this article, though, to critically following up all of these links and dependencies. On the other hand, infectious diseases may spread quickly around the globe given extensive movement of people between countries. Accordingly, many developed countries reacted with emergency aid packages and developed strategies and committed aid at international gatherings, such as G7/8 or G20 summits. As an immediate reaction demonstrating the global awareness of the extent and threat of the Ebola outbreak, in summer 2014, the G7 issued a joint declaration. Here, the G7 foreign ministers said: “We urge the international community to bring high-quality medical care to Ebola patientsWe underscore our willingness to provide relief to the countries ravaged by the virus and emphasize our common 19 understanding that Ebola is a common global threat to peace and security. The website of the German Federal Ministry for Economic Cooperation and Development states that there is a focus “to draw lessons from the fight against Ebola[and that now] the G7 have made a commitment to actively strengthen health systemsbecause crises such as Ebola are much less severe when 20 there are functioning health systems. For example, at the last summit in Germany (Heiligendamm 2007), health had been more or less kicked off the agenda after climate change became the key global issue just prior to the conference. Some governments, particularly the Japanese government, had in the 21 past used the G7/G8 gatherings to emphasize the importance of health systems, but it was difficult to see how it mattered. Among the high-income countries, governments have reacted to the Ebola outbreak by providing substantial amounts of emergency aid (see Table 1). The three most affected countries, Sierra Leone, Liberia and Guinea, all benefited to some extent. Looking at the donor side, apart from a rather small 26 contribution from Germany and Switzerland, France provided all of that support. International (governmental) organizations However, this limited support of health systems coming directly from national governments might not be the whole story. It describes three phases of response, the first of which was focused on tackling the increase in cases as quickly as possible; the second concerned “the rapid scale-up of case finding, contact tracing, and intense community engagement to interrupt residual transmission chains,” and the third phase is about “driv[ing] the number of cases to zero. While important in facilitating the fight against this particular Ebola outbreak, this is clearly not part of a strategy to make more comprehensive health system for the prevention of future outbreaks. However, the World Bank says “the World Bank Group, the World Health Organization, and other partners, are developing a plan for a new Pandemic Emergency Facility that would enable resources to flow quickly 34 when outbreaks occur. The World Bank, in the past, has produced 35 important work on health systems, which makes one wonder to what extent the Ebola response is embedded in, or linked to, broader approaches to the development of health systems within World Bank work and initiatives. The grants and loans from the World Bank were designated to rebuild health systems, social safety nets, and agriculture. In information that was provided to help the most Ebola-affected countries, “strengthening health systems and front line care” is mentioned as one of 36 the five priority areas. The World Bank’s Statement of the Meeting Convening 37 Partners, “From Ebola to More Resilient Health Systems,” proves that in this case, indeed, there seem to be a more practical commitment to health systems. The priority areas of this new funding will be strengthening health systems and frontline care,cash transfers and other social protection programs. Groups of Countries as global social policy actors There are yet other instances of transnational social policies, namely groups of countries or world-regional associations. Particularly China has emphasized the value of 39 its specific approach to development aid. However, the focus is primarily on “getting to zero,” not 44 quite on a longer-term perspective for strengthening health systems. The links between Ebola and health systems appear to be rather rhetorical ones; the share of commitment is very much limited and only visible for very few donor countries. To be fair, the global efforts to fight the disease have now proven to be successful. However, this only solves part of the problem – the economies, social protection, and health systems of those countries that were most affected have suffered in multiple ways, and were not been strong at the outset. The data presented in this article shows how little there is in terms of “real” commitment to supporting long-term processes to develop health systems. As has been illustrated, it is not only very few donors that have explicitly allocated funds to strengthening health systems; the few who have, mainly France, Germany and the World Bank, have committed only a small share of their total spending on Ebola to health systems. The shock and fear that came with this unprecedented spread of the Ebola virus clearly had the potential to change things. The Western world was considerably alert to and worried about the threat of having the disease spread across the globe – a disease that nobody has a cure for, not even those countries with the best health infrastructure and medical procedures. Economic interests, trade links, and real senses of global solidarity also nurtured the efforts to tackle the disease. From that perspective, this global health emergency certainly had a potential to change global health policies. This hints at a number of issues, situated at different levels of social and health policy making in a development context. Despite long and better knowledge about the importance and value of sustainable health systems, most global health initiative continue to target particular diseases and groups (“vertical programs”). Horizontal approaches, including claims to direct development aid for health into the public budgets of countries in order to 46 build better public health systems are not new, but frequently overlooked. At a regional level, there is the problem of the potential of mutual support in a context of common development needs and a common crisis situation. If the regional funding of social and health policy support is dependent on external donors, this limits the control over appropriate measures by regional decision-makers. Furthermore, what needs to be considered is that, due to the difficulties in controlling the spread of the disease at an early stage, the Ebola outbreak generated multiple crises with several social and economic hardships extending to far more parts of the population than the Ebola-affected communities. When the Ebola virus began to spread in some of the least developed countries, fiscal deficits increased in countries with severe structural vulnerabilities and very limited economic growth. Furthermore, imposed travel and trade restrictions caused by the Ebola outbreak put another burden on national economies. It alerts us, though, to the fact that “getting to zero” is not the end of the story. This “renewed” global awareness, if taken seriously, can draw on substantial knowledge and ideas that have been developed over the past decades in a number of international organizations and that are supported by many other global social and health policy actors. The Ebola outbreak created a window of opportunity to get global health policies and actors more committed to supporting health systems to prevent similar future crises, and help the countries that have been strongly affected by the outbreak in multiple ways to recover and improve. Unfortunately, despite even recent statements such as at the G7 in summer 2015, there is not much evidence that there will be much of such a real commitment. The broad consensus on the problem and the danger of weak health systems only illustrated, and have been made worse, by the Ebola crisis. It would need to be turned from a collaborative emergency response to a multi-actor, multi-level long-term commitment. This is what should be at the core of re-constructing global social and health governance, and the Ebola crisis could be the beginning of such a process. What is at stake is reserve funds in the anticipation of future health emergencies and global insurance institutions that provide crisis support in a quick and de-politicized manner. A type of insurance, though with a more general focus on inequality, has also been thought about by Robert J. Shiller as an “innovative scientific finance and insurance, both private and public, to reduce inequality, by quantitatively managing all the risks that contribute to it. Such a fund would have combined emergency response mechanisms with support to health system development. A significant allocation of aid money, though, would need to be committed – the proposal mentions a “multibillion dollar investment 51 channeled to low-income countries”. A similar proposal was made by the World Bank for a pandemic emergency facility that would have money available for future 52 pandemic response, conceptualized as an insurance model. In light of all that, growing out of the Ebola response, it would be welcome to see a more intense engagement with the strengthening of health systems in the framing of the post-2015 development agenda. While this may “represent an important addition to the agenda and has widespread backing from countries and 54 global health institutions,” the question remains if we will see a change at last. The Global Fund to Fight Aids, Tuberculosis and Malaria: Establishment, Current Issues and Future Challenges. It is, however, beyond the scope of this paper to discuss all of these organizations in detail.

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Pediatric autoimmune mate of lifetime psychiatric diagnoses: a methodological study women's health center virginia tech generic premarin 0.625 mg fast delivery. Arch Gen Psychiatry 1986;43: ronal antibody-mediated neuropsychiatric disorders of child 1180–1182 menopause neuropathy 0.625 mg premarin free shipping. Symptoms of obses children with pediatric autoimmune neuropsychiatric disorders sive compulsive disorder menopause hormones buy premarin uk. J Clin Invest analyzed symptom dimensions to women's health issues thrombosis haemostasis purchase premarin online from canada predict outcome with seroto 1989;83:1710–1716. Am J Psy analysis of obsessive-compulsive disorder using symptom-based chiatry 1997;154(3):402–407. Segregation analysis of fever: relationship to streptococcal infection and autoimmune obsessive compulsive and associated disorders. Lack of association analysis for obsessive compulsive disorder and related disorders. Neuropsychobiology 1994;29: compulsive symptoms in Gilles de la Tourette’s syndrome and 61–63. Nat Genet the seven-repeat variant of the dopamine D4 receptor gene in 1993;3:4–5. Serotonin transporter patients diagnosed with velo-cardio-facial syndrome and their and seasonal variation in blood serotonin in families with obses relatives. Obsessive compulsive does a hemizygous deletion of chromosome 22q11 result in disorder, response to serotonin reuptake inhibitors and the sero bipolar affective disorder These are only available if your state or district has included them in your particular testing program. Comparison of Accommodations Use the chart below to determine which option is appropriate for examinees. What options Extended time or additional breaks: these options are available: Extended time or additional breaks: are available Refer to the Ordering State-Allowed approval Approved Accommodations section Accommodations Materials section required Ordering Practice Materials You may order alternate format practice materials at no charge at: media. If a reconsideration request is submitted after the deadline, decisions will not be available for the scheduled test event. Notification of Reconsideration the reconsideration decision will be in an updated Accommodations Decision Notification. When the updated Accommodations Decision Notification is available to view online, the individual who submitted the reconsideration request will receive an email. Plan Information You will enter this plan information: • the type of plan in place for the examinee • if the plan has been in place less than one year, or one year or more Accommodations Information You will select appropriate alternate format materials and timing. Note: If the examinee needs an accommodation that is not listed as an option on the online form, you may type in requests for other accommodations. Refer to the Completing the Accommodations Section of the Request below for information about test packages. In addition, this documentation may be required: • a psychoeducational/neuropsychological evaluation • a qualified professional diagnosis • a complete evaluation You may upload any relevant information under “other documentation. Professional Diagnosis the disability must be diagnosed by a qualified professional with credentials appropriate to the diagnosis. A psychologist, psychiatrist, physician, or learning disabilities specialist/team may diagnose learning disabilities. Documentation Requirements Documentation must be written by the diagnosing professional and must meet all of these guidelines: • states the specific impairment as diagnosed • is current (diagnosed or reconfirmed within three academic years) • describes presenting problems and developmental history, including relevant educational and medical history • describes substantial limitations (adverse effects on learning, or other major life activities) resulting from the impairment, as supported by test results • describes recommended accommodations and provides rationale explaining how these specific accommodations address the substantial limitations • establishes the professional credentials of the evaluator, including information about licensure or certification, education, and area of specialization • includes comprehensive assessments (neuropsychological or psychoeducational evaluations), with evaluation dates, used to arrive at the diagnosis the information below indicates the required documentation for each condition. Confidentiality of Documentation Documentation will be kept confidential and used solely to review accommodations requests. At the onset, all patients presented with at least, one psychiatric manifestation including anxiety, emotional lability, bedwetting, enuresis, and phobia, and oppositional behavior including temper tantrums, personality changes, and deterioration in math skills and handwriting. Auto-antibodies might be responsible for targeting brain structures, such as Introduction dopamine D1 and D2 receptors, leading to the Streptococcal infections in children are very alteration of dopaminergic transmission [12]. More recently, a condition has been that assessment of D2 receptor antibodies may related to streptococcal infection: the pediatric be useful in defning autoimmune movement autoimmune neuropsychiatric disorder associated and psychiatric disorders. In Methods Tables 1-3, the single clinical features and psychiatric manifestations are reported. At the these discordances may be due to the diferent diagnosis, laboratory and diagnostic evaluation strains of involved streptococci. Nightmares 2 The software was created with runs in the Cloud Fear of being abandoned before sleeping 2 to obtain data rapidly, and to gain even more Obsessive thoughts 2 information in further studies. Bad school results 2 Psychotic symptoms 2 Results Trash talking 1 Compulsive and repetitious gesture 1 A total of 34 patients include 18 males and Unusual gesture 1 16 females, with an average age of 9. Stranger refuse 1 All patients showed at least one psychiatric Abandonment issue 1 manifestations, specifcally anxiety, enuresis, Severe food selectivity 1 phobia, oppositional behavior. Choreiform movements of the arms 2 The course is variable with diferent phases, Hang up 1 depending on the re-appearance of new infection Flexion-extension of the wrist 1 [1-5]. This represents All patients showed impressive tics in high an exciting gap that future research will be able frequency which tends to vary in intensity during to bridge. The study performed dynamic neurological and psychiatric disorders, Gadian positron emission tomographic study using et al. Further studies need to temporary improvement of clinical symptoms, be performed to better understand pathogenesis with their reappearance within 1 to 6 months. Limitations of Acknowledgments the present study include the absence of case controls and long-term follow up. This study was showed various psychiatric problems and supported by a grant from Samsung Medical Center tics. Child Ado disorders associated with streptococcal tion of a Neuropsychiatric Disorder: From lesc. Frankovich J, Thienemann M, Pearlstein J, autoimmune sequelae: Rheumatic fever atic review of literature data. Streptococcus Pyogenes: neuropsychiatric syndrome: presenting Basic Biology to Clinical Manifestations 16. Frankovich J, Thienemann M, Rana S, et search subgroup to clinical syndrome: Mod (2014). The link between autoimmune Associated with Streptococcal Infections diseases and obsessive-compulsive and tic 18. Behavioral, pharmacological, and immu ed with streptococcal infection: Sydenham nological abnormalities after streptococcal 19. Clinical presentation of pediatric autoim mune neuropsychiatric disorders associat 13. Clinical Management of Pediatric Acute Immunoglobulin for Pediatric Autoimmune Psychopharmaco 25(1), 65-69 (2015). Through this organization, which was created in 1948, the health professions of some 180 countries exchange their knowledge and experience with the aim of making possible the attainment by all citizens of the world by the year 2000 of a level of health that will permit them to lead a socially and economically productive life. Progress towards better health throughout the world also demands international cooperation in such matters as establishing standards for biological substances, pesticides and pharmaceuticals; formulating environmental health criteria; recommending international nonproprietary names for drugs; administering the International Health Regulation; revising the International Statistical Classification of Diseases and Related Heath Problems; and collecting and disseminating health statistical information. Applications and enquiries should be addressed to the Office of Publications, World Health Organization, Geneva, Switzerland, which will be glad to provide the latest information on any changes made to the text, plans for new editions, and reprints and translations already available. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. It stimulated and conducted research on criteria for classification and for reliability of diagnosis, and produced and promulgated procedures for joint rating of videotaped interviews and other useful research methods. The programme activities also resulted in the establishment of a network of individuals and centres who continued to work on issues related to the improvement of psychiatric classification (1,2). The 1970s saw further growth of interest in improving psychiatric classification worldwide. Expansion of international contacts, the undertaking of several international collaborative studies, and the availability of new treatments all contributed to this trend. Several national psychiatric bodies encouraged the development of specific criteria for classification in order to improve diagnostic reliability. In particular, the American Psychiatric Association developed and promulgated its Third Revision of the Diagnostic and Statistical Manual, which incorporated operational criteria into its classification system. A series of workshops brought together scientists from a number of different psychiatric traditions and cultures, reviewed knowledge in specified areas, and developed recommendations for future research. A major international conference on classification and diagnosis was held in Copenhagen, Denmark, in 1982 to review the recommendations that emerged from these workshops and to outline a research agenda and guidelines for future work (4).

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Physicians should document the diagnosis and indication for Xyrem pregnancy nutrition trusted 0.625mg premarin, being alert to pregnancy zicam purchase premarin 0.625mg with visa drug-seeking behavior and/or feigned cataplexy menopause type 7 purchase premarin no prescription. In the first case women's health clinic portage order premarin canada, an estimated dose of 150 g, more than 15 times the maximum recommended dose, caused a patient to be unresponsive with brief periods of apnea and to be incontinent of urine and feces. In the second case, death was reported following a multiple drug overdose consisting of Xyrem and numerous other drugs. Patients have exhibited varying degrees of depressed consciousness that may fluctuate rapidly between a confusional, agitated combative state with ataxia and coma. Recommended Treatment of Overdose General symptomatic and supportive care should be instituted immediately, and gastric decontamination may be considered if co-ingestants are suspected. No reversal of the central depressant effects of sodium oxybate can be expected from naloxone or flumazenil administration. However, due to the rapid metabolism of sodium oxybate, these measures are not warranted. Poison Control Center As with the management of all cases of drug overdosage, the possibility of multiple drug ingestion should be considered. The physician is encouraged to collect urine and blood samples for routine toxicologic screening, and to consult with a regional poison control center (1-800 222-1222) for current treatment recommendations. The starting dosage can then be increased to a maximum of 9 g/night in increments of 1. One to two weeks are recommended between dosage increases to evaluate clinical response and minimize adverse effects. The efficacy and safety of Xyrem at doses higher than 9 g/night have not been investigated, and doses greater than 9 g/night ordinarily should not be administered. Each dose of Xyrem must be diluted with two ounces (60 mL, cup, or 4 tablespoons) of water in the child-resistant dosing cups provided prior to ingestion. The second dose must be prepared prior to ingesting the first dose, and should be placed in close proximity to the patient’s bed. Because food significantly reduces the bioavailability of sodium oxybate, the patient should allow at least 2 hours after eating before taking the first dose of sodium oxybate. Hepatic Insufficiency Patients with compromised liver function will have increased elimination half-life and systemic exposure along with reduced clearance (see Pharmacokinetics). As a result, the starting dose should be decreased by one-half and dose increments should be titrated to effect while closely monitoring potential adverse events. Preparation and Administration Precautions Each bottle of Xyrem is provided with a child resistant cap. The pharmacy provides two 90 mL dosing cups with child-resistant caps with each Xyrem shipment. This means that if you sell, distribute, or give your Xyrem to anyone else, or if you use your Xyrem for purposes other than what it was prescribed for, you may be punished under federal and state law by jail and fines. Abuse of Xyrem can lead to dependence, craving for the medicine, and severe withdrawal symptoms. Do not take Xyrem if you: • Take other sleep medicines or sedatives (medicines that cause sleepiness) • Have a rare condition called succinic semialdehyde dehydrogenase deficiency. Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and supplements. See “Directions for using Xyrem” at the end of this Medication Guide for detailed information about taking Xyrem. If you miss the second dose, skip that dose and do not take Xyrem again until the next night. Patients that already have breathing or lung problems have a higher chance for breathing problems with Xyrem. Call your doctor right away if you have: • confusion • psychosis (seeing or hearing things that are not real) • abnormal thinking • agitation • depression • thoughts of killing yourself or try to kill yourself • bedwetting. The most common side effects with Xyrem are nausea, dizziness, and headache, vomiting, sleepiness and bed-wetting. General advice about Xyrem Medicines are sometimes prescribed for purposes not mentioned in Medication Guides. Step 1 Remove the Xyrem bottle and the measuring device from the box (See Figure 1). Empty each Xyrem dose into a dosing cup, then add about 2 ounces of water (60 mL, cup, or 4 tablespoons) to each cup (See Figure 6). Place the caps provided on the dosing cups and turn each cap clockwise (to the right) until it clicks and locks into its child-resistant position (See Figure 7). Recap the Xyrem bottle and store it in a safe and secure place (locked up if needed), out of the reach of children and pets. Set an alarm to go off 4 hours after your first dose to wake you up for your second dose. While sitting in bed, drink all of the second dose right before lying down to continue sleeping. If not, the pharmacy will provide verbal education and supply patient education material with the first prescription. If the courier tracking service were to indicate a discrepancy from either the patient’s or designee’s name, the pharmacy will contact the patient directly by phone to ensure delivery • the package will be sent under condition that if the patient or his/her designee is unavailable to accept a shipment of Xyrem and execute the required receipt after two delivery attempts, the package will be returned to the pharmacy. In addition, you have agreed that: • If a prescription refill is requested by the patient prior to the anticipated due date, such refills will be questioned by the pharmacist. The pharmacist has the discretion to grant or not grant refill requests under those circumstances and at a minimum will contact the prescribing physician to determine if the physician has any special concerns in regard to that refill request. Xyrem Physician Success Program this program consists of printed material(s) to educate physicians about the features of Xyrem. Xyrem Patient Success Program this program consists of a videotape and printed educational material, which patients will receive from their physician or the pharmacy, prior to or together with the first shipment of drug. The pharmacy will confirm that the patient has read and/or understood the educational materials. Before Prescribing Xyrem • Prescribing Xyrem requires entry into a physician registry. Each patient’s dose may be titrated within the effective dose range of 6 to 9 grams/night. Refills (circle one): 0 1 2 3 4 5 Date: / / Prescriber’s Signature Please check each box To be completed at initial prescription only I verify that the patient has been educated with respect to Xyrem preparation, dosing and scheduling. I verify that the patient has received his/her own copy of the Patient Success Program materials (optional). The Xyrem Success Program includes: Patient Support • Pharmacy services are provided by a central pharmacy, which handles all insurance coverage, product dispensing, mail order delivery and patient counseling. On the enclosed Physician Registration Form, please confirm that: 1) you have read the enclosed materials; 2) you understand Xyrem is approved for the treatment excessive daytime sleepiness and cataplexy in patients with narcolepsy; and 3) you understand that the safety of doses greater than 9 g/day has not been established. This form should be filled out completely to ensure timely fulfillment of your patient’s prescription by the pharmacy. You should also provide each patient with the Xyrem Patient Success ProgramP materials. These records will be made available to any state or federal agency that requests them. Chief Medical Officer Vice President Clinical Research and Medical Affairs Jazz Pharmaceuticals, Inc. P I understand that XyremP (sodium oxybate) oral solution is approved for the treatment ofP excessive daytime sleepiness and cataplexy in patients with narcolepsy, and that safety or efficacy has not been established for any other indication. This booklet answers important questions about obtaining, using, and storing Xyrem and precautions to be considered when doing so. If your physician did not provide these materials to you, the pharmacy will review them with you before sending your first shipment of Xyrem. When the courier arrives you, or someone you designate, must sign for your Xyrem delivery. Because Xyrem is a controlled substance, it is illegal for you to sell or give your Xyrem to anyone else, or to use your Xyrem for purposes other than it was prescribed. An experienced Reimbursement Specialist will: • call you to review your benefits and eligibility. The pharmacy’s attempt to obtain coverage from a patient’s third-party payer does not constitute or guarantee success.

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