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Importantly hiv infection rate germany cheap 200mg acivir pills, however antiviral lubricant generic acivir pills 200 mg mastercard, this study showed that cessation of symptom-onset treatment was not associated with discontinuation symptoms hiv symptoms days after infection cheap 200 mg acivir pills visa. Side effects may be less frequent with an intermittent dosing regimen because they may not occur when not taking the medication hiv infection through needle prick buy 200mg acivir pills amex. Dosing should be strictly limited to the luteal phase antivirus worth it safe acivir pills 200 mg, and the patient should have no history of substance abuse hiv infection symptoms generic acivir pills 200mg mastercard. Improved symptoms included anxiety, depression, water retention, and somatic changes. Patients with more severe symptoms before treatment were the most likely to relapse, while patients who experienced symptom remission with treatment were least likely to relapse. Continuous dosing and luteal phase dosing regimens are similarly effective for these disorders when the symptoms are clearly limited to the luteal phase of the menstrual cycle. Several new oral contraceptives that decrease or omit the placebo interval, calcium supplementation, and cognitive behavioral therapy may provide an effective alternative to antidepressant medications. American Psychiatric Association: Diagnostic and statistical manual of mental disorders. Subserosal leiomyomas can grow in a pedunculated fashion from the uterus as they enlarge. Leiomyomas arise during the reproductive years, can enlarge during pregnancy, and regress following menopause. Risk Factors Factors associated with increased risk of leiomyomas include early age of menarche, alcohol intake, nulliparity, obesity, family history, age, hypertension, and African descent. Factors associated with decreased risk for leiomyomas include depot medroxyprogesterone (Depo Provera) use, increased parity, and menopause. Pathophysiology Leiomyomas arise from a unicellular origin in the smooth muscle of the myometrium. Leiomyomas have a relatively poor vascular supply of one or two arteries at the base of the leiomyoma, which can result in a tumor outgrowing its blood supply. Growth hormones act synergistically with estradiol in affecting the growth of leiomyomas. Menstrual abnormalities are the most common symptoms associated with the presence of myomas. Pelvic pain and pressure can be the result of a large leiomyoma alone or from vascular compromise. Chronically, women can experience the sensation of pressure from an enlarged uterus. Acute pain from vascular compromise can occur when pedunculated myomas torse, when hemorrhage occurs within a myoma (usually in association with pregnancy), or when a myoma outgrows its blood supply. Obstructive symptoms affect the urinary system (urinary frequency or urgency) more commonly, but they can also cause rectal symptoms like constipation. Some experts recommend the treatment of submucosal leiomyomas that distort the uterine cavity because they may impair in vitro fertilization. There is uncertainty regarding the possible role leiomyomas play in early miscarriage. Diagnosis Uterine leiomyomas (also referred to as leiomyomas or myomas) are benign smooth-muscle tumors. References interstitial (within the myometrium), and submucous (just below the endometrium). The incidence of leiomyomas identified via ultrasound scanning is about 5% in young adults, 15% in middle-aged women, and 30% in women older than 40 years. Leiomyomas produce a dysregulation of growth factors and their receptors, causing vascular abnormalities that can contribute to the symptom of menorrhagia. They can also be found in association with menorrhagia, dysmenorrhea, pelvic pain and pressure, obstructive symptoms, infertility, and pregnancy loss. Menorrhagia is the most common bleeding pattern and can result in an iron deficiency anemia. These manifestations are more common during pregnancy in the setting of large leiomyomas and uterine enlargement. There is also some evidence that spontaneous conception rates may improve after myomectomies of submucosal fibroids. There is a lack of evidence at this time that these treatments result in statistically significant differences in live birth rates. Epidemiology the bimanual examination finding of an enlarged and irregularly shaped uterus is often the first indication that a patient has leiomyomas. Transvaginal sonography has the lowest sensitivity and specificity, but it is the best initial test based on its noninvasiveness and cost-efficiency. Sonohysterography and hysteroscopy can be used to evaluate the extent of submucosal leiomyomas, but these methods are invasive. Differential Diagnosis Patients consult physicians because of symptoms related to leiomyomas or when the lesions are diagnosed incidentally during physical or radiologic examinations. Attributing symptoms to uterine leiomyoma with certainty is complicated owing to their high prevalence and because the differential diagnosis for symptoms related to leiomyomas is wide. For example, possible causes of menorrhagia include pregnancy, infection, carcinoma, and endocrine, hematologic, physiologic, systemic, structural, and iatrogenic causes. Differentiating leiomyoma from malignant leiomyosarcoma can be challenging as rapid growth alone is not an adequate marker. Treatment Expectant Management Expectant management is the treatment of choice for women with asymptomatic leiomyomas regardless of size. Early intervention may be an option for asymptomatic young women desiring future fertility because leiomyoma tumors can become larger with the passage of time, thereby complicating treatment in the future. There is no evidence that low-dose contraceptives cause the growth of uterine leiomyoma tumors; thus fibroids are not a contraindication to their use. This therapy is best suited for women in the perimenopausal or preoperative periods owing to significant side effects resulting from hypoestrogenism. Mifepristone (Mifeprex) decreases bleeding and improves quality of life, but does not affect fibroid volume. Luipristal (Ella) is approved as an emergency contraceptive in the United States, but has been used in Europe for years as a treatment for fibroids pending surgery. The aromatase inhibitor letrozole has been shown to decrease fibroid size and reduce bleeding without vasomotor symptoms, or changing bone density. Larger clinical trials are needed to fully evaluate safety and efficacy of letrozole for this indication. Surgical Treatments Selected patients can benefit from surgery: those with persistent abnormal uterine bleeding or symptoms resulting from uterine bulk that do not respond to conservative measures or when the diagnosis of leiomyosarcoma is being considered. Abdominal or vaginal hysterectomy is the definitive treatment for symptomatic uterine leiomyomas. Benign pigmented lesions, such as nevi and seborrheic keratoses, may occasionally be found. Malignancy is rare, but most should be excised for diagnostic and therapeutic purposes. When myomectomies are performed to preserve fertility, care must be taken to avoid adhesions, which can compromise the goal of the operation. Currently, many clinicians recommend cesarean section for all pregnancies after myomectomy despite limited data to support this recommendation. Postprocedure pain is significant, generally requiring admission at least overnight for narcotic analgesia. Postprocedure complications include postembolization syndrome (pain accompanied by fever, nausea, and vomiting); injury to the ovary, ureter, or other structures (misembolization); and infection. Long-term outcomes have been encouraging: 73% of women had continued symptom control at 5 years in one study. Myolysis involves techniques designed to destroy rather than remove leiomyoma tumors. Whether benign or malignant, vulvar neoplasms are uncommon, occur at all ages, and have varying characteristics. If the cyst is symptomatic or infected, however, drainage, marsupialization or use of a Word catheter, is indicated. Viswanathan M, Hartmann K, McKoy N, et al: Management of Uterine Leiomyomas: An Update of the Evidence, Evidence Report/Technology Assessment No. Representative biopsies should be obtained to document disease and rule out malignancy. The choice of surgical approach largely depends on the expertise of the physician. Uterine artery embolization uses interventional radiology to occlude the uterine arteries with polyvinyl alcohol microspheres positioned by a catheter passed through the femoral artery. Short-term outcomes demonstrate that uterine artery embolization has lower morbidity than hysterectomy, but readmission rates are high: 5% to 10%. The issue of fertility after uterine artery embolization is still under investigation. The female external genitalia includes the mons pubis, labia majora, labia minora, clitoris, perineal body, and the structures of the vaginal introitus or vestibule. Therefore liberal use of biopsies is usually required for diagnosis and treatment decisions. Cysts of the canal of Nuck are located in the anterior portion of the labia majora at the termination of the insertion of the round ligament. These cysts represent herniation of the peritoneum through the inguinal canal and contain peritoneal fluid. If symptomatic, excision must be accompanied by closure of the fascial defect to prevent recurrence. Podofilox is applied twice daily for 3 days, repeated weekly for 4 weeks and imiquimod is applied three times per week for up to 16 weeks. Providers may instead choose in-office application of trichloroacetic acid (TriChlor), 5-fluorouracil1 (1%, Fluoroplex or 5%, Efudex),1 or podophyllin. Podophyllin and 5-fluorouracil should not be used in women who could become pregnant. These risk factors include early first intercourse, multiple sexual partners, smoking, and immunosuppression. Symptoms of both types include pruritus (most common), pain, a noticeable lesion, and discoloration. Typical findings are raised white, gray, red, or mottled lesions; application of 4% acetic acid for several minutes can help identify faint lesions and outline abnormal vascular patterns. Management should be individualized to each patient taking into account risk of progression, distribution of disease and histologic features on biopsy. Patients at risk for microinvasion (unifocal disease, raised lesions, older age, and prior radiation) should have the lesion excised completely if possible. Skinning vulvectomy is rarely used because of psychological and sexual consequences related to scarring and disfigurement. Both can ablate large or multifocal lesions successfully with an excellent cosmetic and functional outcome. An alternative ablative therapy is use of imiquimod1 (Aldara), as described earlier. Because of the irritation caused by these topical therapies, many patients have problems with treatment compliance. Continued smoking increases this risk, so patients should be counseled in smoking cessation. In those patients whose cancers recur and are retreated, subsequent 5-fluorouracil prophylaxis, with a single application biweekly, is used successfully to minimize further recurrences. In addition, up to 30% of patients have a synchronous adenocarcinoma of the breast, colon, rectum, or upper genital tract. To assess for invasion, the lesion should be excised via wide local excision or simple vulvectomy with at least 5 mm of the adjacent subcutaneous tissue. However, the risk of recurrence is approximately 30% whether margins are negative or positive. Thus expectant management, reserving treatment for symptomatic recurrences, is usually recommended. Invasive Vulvar Lesions 1144 Less than 5% of gynecologic cancers arise on the vulva. Most patients present with a combination of symptoms, including pruritus, discomfort, and complaints of a mass. Examination frequently reveals a suspicious lesion, which should be biopsied for diagnosis. Factors that influence dissemination include tumor size (Table 2), depth of invasion (Table 3), lymphovascular space invasion, and tumor grade. It is a variant of squamous carcinomas but has an excellent prognosis because of the lack of metastases. Verrucous carcinomas have a high tendency to recur and should be managed with radical local excision. Malignant Melanoma Malignant melanoma is the second most common vulvar malignancy.
Cancer of the Endometrium 1113 Monitoring Surveillance recommendations for endometrial cancer are stratified by risk of recurrence antiviral drugs classification purchase acivir pills 200 mg on-line, and most women diagnosed and treated for endometrial cancer will fall into the low-risk category hiv infection vomiting discount acivir pills 200mg on-line. High risk for recurrence is defined as advanced stage or grade 3 endometrioid hiv opportunistic infection guidelines discount acivir pills 200 mg otc, serous hiv infection rates us 2012 order acivir pills mastercard, or clear cell histology hiv infection rates map cheap acivir pills 200mg free shipping. Follow-up recommendations for low-risk women involve a history and physical examination hiv stages of infection 200 mg acivir pills overnight delivery, including a speculum and pelvic examination, scheduled every 6 months for the first 2 years, then yearly. If all children younger than 12 years were vaccinated, the most optimistic predictions expect a major effect on the cancer incidence will not be seen for 30 years. It is the greatest cancer killer of young women and the most common cause of death from cancer in women in the developing world. Significant disparities in incidence and stage at time of diagnosis have been identified among different ethnic groups-African Americans, Asian Americans, European Americans, and Latin Americans-in the United States. The current standard screening algorithm in the United States for preventing cervical cancer is presented in Table 1. The colposcopic examination is used to guide biopsies of the exocervix, and in most cases an endocervical biopsy is also performed. Worldwide in 2008, among the 530,000 new cases of cervical cancer, the highest incidence rates were in Africa, Central and South America, and Asia. In the United States, it is estimated that approximately 12,200 new cases were diagnosed and 4,210 patients died from cervical cancer in 2010. Patients with this extent of disease can safely be treated with a less-radical hysterectomy, an extrafascial hysterectomy. Pelvic lymphadenectomy is not recommended owing to the low risk of pelvic node metastasis (<1%). The 5-year survival was 98% among 568 who underwent cone biopsy alone versus 99% among 841 who underwent hysterectomy. In patients with highrisk criteria after surgery-positive surgical margin, parametrial involvement, and positive pelvic nodes-cisplatin-based1 chemoradiation, based on a positive randomized trial, is recommended. Those with intermediate risk factors including tumor size, cervical stromal invasion, and lymphovascular invasion had an improved progression-free survival with adjuvant radiation. The criteria used for patient selection include early-stage cervical cancer with a lesion less than 2 cm, no lymphovascular invasion, and no lymph node metastasis. Reports comparing radical trachelectomies with matched controls identified increased complications (25% vs. It is estimated that approximately 35% of patients with invasive cervical cancer will have recurrent or persistent disease, with most recurrences occurring in the first 2 years following primary therapy. Recurrence can be expected in 10% to 20% of patients treated with radical hysterectomy in contrast to 30% to 50% treated for more-advanced disease primarily with radiation plus concurrent chemotherapy. This staging is based on a careful clinical examination and the results of specific radiologic studies and procedures. In cervical cancer, primary lesions initially progress to lymphatics in the parametrium and pelvic nodes and then extend laterally to the pelvic side wall, bladder, and rectum. The two major spread patterns identified in cervical cancer include direct extension and lymphatic spread. Diagnosis the initial workup for cervical cancer depends on whether a cervical lesion is visible. Patients with a cervical lesion are assessed by history and physical examination and possibly by examination under anesthesia for biopsy, cystoscopy, sigmoidoscopy, and conventional imaging (chest x-ray, intravenous pyelogram). Prognosis is more favorable for patients undergoing exenteration when there is a small (<3 cm) central recurrence, no sidewall involvement, and longer than 2 years of disease-free interval. Those with small recurrences limited to the cervix or upper vagina can occasionally be treated with radical hysterectomy and upper vaginectomy. However, most recurrences are distant, involving the lung, bone, abdominal cavity, and supraclavicular lymph nodes. Recurrences in the nonirradiated areas respond better to chemotherapy, with response rates of 25% to 70%. The use of chemotherapy in the treatment of recurrent cervical cancer is challenging because agents are only moderately active and patients can present with renal impairment secondary to obstructive uropathy, resulting in altered excretion with increased toxicity from chemotherapeutic agents. Table 4 compares results of randomized chemotherapy trials for the treatment of recurrent cervical cancer. They provide excellent cycle control and decreased rates of ectopic pregnancy, pelvic inflammatory disease, and endometrial and ovarian cancer, and they can be used in extended-cycle methods for patients who desire fewer than 12 periods per year. Contraception Adherence to current screening guidelines should allow early cervical cancer or precancerous detection. However, most patients with cervical cancer have not participated in regular screening and present with a variety of disease extents. Nearly half of all pregnancies in the United States are unplanned, a rate higher than the rate in other developed countries. Primary care physicians need up-to-date knowledge on contraceptive counseling for women in order to provide the best match between patient and contraceptive method, in part because providers frequently need to supply contraceptives to women who have particular medical comorbidities. Newer contraceptive preparations are now available, including long-acting implants and altered oral formulations, which differ from traditional oral contraceptives in their hormonal dosages, cycle length, and hormone-free intervals. Common barrier methods include male and female condoms, spermicides, vaginal sponges, diaphragms, and cervical caps (Table 1). Barrier methods have the lowest efficacy rates of all contraceptive methods, and users should also be counseled about emergency contraception. Benefits in addition to menstrual control include reduction in the risks for, and symptoms of, endometriosis, ovulatory pain, ovarian cysts, benign breast disease, premenstrual syndrome, and premenstrual dysphoric disorder. Spotting, unscheduled bleeding, or absence of bleeding Consider in: Women who do not desire monthly periods. Fewer withdrawal bleeds per year and shorter placebo may offer particular benefit for women with estrogen withdrawal symptoms, dysmenorrhea, or endometriosis. Women with contraindication to estrogen, seizure disorder, hypercoagulable states, dysmenorrhea, migraine with aura, or breast-feeding. In addition to estrogen dose and scheduling, it is also important to consider the progestin component, which theoretically may affect libido, weight gain, acne, and hirsutism. The different formulations offer patients options in cycle length, hormone levels, duration of withdrawal bleeding, and side-effect profile. If 2 days of pills are missed, she should take two pills daily for 2 days in a row and use a backup method. If 3 days of pills are missed, she should discard the pill pack and use a backup method. At that point, it should be discussed whether to start a new pack or to change contraceptive methods. Extended-cycle regimens have other benefits, including decreased hormone withdrawal symptoms such as headaches, tiredness, bloating, excessive bleeding, or menstrual pain. Norelgestromin/ethinyl estradiol (Ortho Evra) is a thin transdermal patch containing 75 mcg of ethinyl estradiol and 6 mg of norelgestromin; it delivers a daily dose of about 20 mcg of estrogen and 150 mcg of progesterone daily. Patches should be changed weekly for 3 weeks on "patch change day" followed by a patch-free week during which menses occur. Only one patch should be worn at a time, and no more than 7 days should pass during the patch-free week. A new ring is inserted 7 days after the last was removed even if bleeding is not complete. Most women find the ring easy to insert and remove and comfortable to retain during intercourse. All progestin-only methods have a similar method of action: ovulation is variably inhibited, cervical mucus is thickened, and the endometrial lining undergoes histologic alterations making implantation less likely. In fact, most experts believe fertility can return in as little as 3 hours after a missed dose; thus a woman should be counseled to use a backup method if she is 3 or more hours late in taking her dose. Given this small window for error, this method should be prescribed only to patients who can adhere closely to a daily pill schedule. This unpatterned bleeding is likely one of the greatest obstacles to wider use of progestin-only oral contraception. Depo-Provera may also decrease seizure frequency, providing additional benefit for patients who have a seizure disorder. The World Health Organization has recommended that there be no restriction on the use of Depo-Provera in women ages 18 to 45. At the time of placement, women may have cramping and pain; a rare complication of placement is uterine wall rupture. Though women will likely develop amenorrhea, they should be counseled about initial irregular bleeding and spotting. Women experience a quick return to normal cycles after implant removal, and there have been no reports of infertility after removal. The most common bleeding pattern associated with the implant is infrequent, irregular bleeding. Each sterilization procedure has advantages and disadvantages that should be considered by the patient before choosing which one to use. Counseling When counseling patients about their contraceptive choices, it is important that providers are aware of their role in giving information and allowing patients to make informed decisions. Providers must educate patients regarding the advantages and disadvantages of each method that is medically appropriate for them. Providers should counsel patients on expected side effects as well as expectant management strategies. Every effort should be made to remove barriers to initiation, including having no requirement for a pelvic examination or Pap smear before initiation. During adolescence, dysmenorrhea leads to high rates of school absence and activity nonparticipation. According to representative national survey data in the United States, 14% of adolescent girls aged 12 to 17 years frequently miss school because of menstrual cramps. A prospective cohort study showed that the prevalence and severity of dysmenorrhea was lower at 24 years of age than at 19 years of age. At 24 years of age, 67% of the women still experienced dysmenorrhea, and 10% reported pain severity that limited daily activity. There is a significant correlation between the severity of dysmenorrhea and the amount of menstrual flow. Survey data demonstrate that depression and anxiety are associated with menstrual pain and suggest that loss of social support is a significant contributor to menstrual symptoms. The severity of dysmenorrhea is not associated with height, weight, or regularity of the menstrual cycle. The association between dysmenorrhea and endometriosis is uncertain for women with minimal disease. Sexually active adolescents and young women should be screened for chlamydia and gonorrhea, which can be done with either urine or a genital sampling. In one study in which diclofenac (Voltaren) 100 mg was compared with placebo for treatment of primary dysmenorrhea, the Dysmenorrhea appropriate for them. World Health Organization: Cardiovascular disease and use of oral and injectable progestogen-only contraceptives and combined injectable contraceptives. The clinical standard for diagnosis of endometriosis is laparoscopic confirmation. Primary dysmenorrhea occurs without underlying pathology, typically beginning soon after menarche. It is common in adolescent girls, with prevalence ranging from 20% to 90% depending on measurement methods; about 15% of adolescents describe their dysmenorrhea as severe. The prevalence and severity of dysmenorrhea were reduced in women who were parous at 24 years and nulliparous at 19 years, but they were unchanged in women who were still nulliparous or women who had had a miscarriage or abortion. Physical activity has been studied and found not to be associated with any pain parameter. Secondary dysmenorrhea typically starts later in life after the onset of an underlying causative condition, most often endometriosis. However, based on a study of more than 1000 women with laparoscopically confirmed endometriosis, chronic pelvic pain, dyspareunia, and dysmenorrhea are in fact related to the extent of endometriosis. For adolescents and women who do not have a history consistent with primary dysmenorrhea or who are refractory to treatment, endometriosis may be suspected. However, the available evidence had little power to detect such differences, because most individual comparisons were based on few small trials. In one study in which diclofenac (Voltaren) 100 mg was compared with placebo for treatment of primary dysmenorrhea, the Dysmenorrhea authors found that leg strength and aerobic capacity were maintained at the level found during luteal phase when women took diclofenac for dysmenorrhea, but they were reduced during menses in the placebo group. Celecoxib (Celebrex) 200 mg was compared with naproxen sodium (Naprosyn) 550 mg and placebo for treatment of dysmenorrhea and found to be superior to placebo but not as effective as naproxen. Etoricoxib (Arcoxia)5 120 mg daily was found to be better than placebo and equivalent to mefenamic acid (Ponstel) for treatment of primary dysmenorrhea with less nausea and epigastric pain than mefenamic acid. Lumiracoxib (Prexige)5 200 mg daily was compared with naproxen 500 mg twice daily and placebo for treatment of primary dysmenorrhea and found to reduce pain more than placebo and similar to naproxen. In a study of women with laparoscopically proven endometriosis, low-dose ethinyl estradiol and norethisterone (norethindrone) decreased dysmenorrhea associated with endometriosis as compared with placebo (with pain assessment on a verbal rating scale from 0 to 3). They include Psidii guajava extract7 6 mg/day, French maritime pine bark extract (pycnogenol),7 and ginger root powder7 250 mg 4 times daily. Acupressure and Acupuncture the evidence for the effectiveness of acupuncture is not conclusive. In unblinded studies women experience clinically relevant reduction in pain scores, a mean of more than 10 points on a 100-point scale, which could be due to placebo effect. Several other studies suggest that acupressure at the Sanyinjiao point or Taichong point is more effective than no intervention or inadequately blinded control groups. Because acupressure is a low-cost and harmless intervention, it may be worth considering even if the pain reduction is a placebo response.
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Local heat hiv infection odds order 200mg acivir pills with visa, putting the affected muscle on stretch timeline for hiv infection buy acivir pills now, acetaminophen hiv infection using condom purchase acivir pills overnight, and massage can be helpful in acute events antiviral for chickenpox discount 200mg acivir pills visa. The exception to this rule is found in patients who have a known placenta previa hiv infection rates south africa discount acivir pills 200mg on-line, are experiencing uterine bleeding antiviral foam buy acivir pills 200 mg with amex, or have postcoital cramps and spotting. It may be wise to avoid intercourse in couples who are at risk for special circumstances. Firmer recommendations can be made in instances of placenta previa or known rupture of membranes; in these instances intercourse should not occur. However, dental procedures under local anesthesia may be carried out at any time during the pregnancy. Antibiotics are appropriate as needed for dental infections and in cases of rheumatic heart disease or mitral valve prolapse with regurgitation. X-rays, Ionizing Radiation, and Imaging the adverse effects of ionizing radiation are dose dependent, but there is no single diagnostic procedure that results in a dose of radiation high enough to threaten the fetus or embryo. Still, the need for x-ray films should be evaluated for risks and potential benefits in the individual pregnant patient to conservatively protect the mother and fetus from theoretical genetic or oncogenic risk. Immunization Live virus vaccines must be avoided during pregnancy because of possible effects on the fetus. The inactivated influenza vaccine (Fluzone, Fluvirin, Fluvarix) is also recommended in all women during any trimester they will be pregnant during the flu season (or up to 3 months postpartum during flu season). Tests of Fetal Well-Being A primary goal in antepartum care is the competent management of patient care extended to both mother and baby in order to reduce the risk of fetal demise after 24 weeks, ensure optimal conditions for term delivery after 37 weeks, and intervene for evolving conditions threatening the well-being of either patient. Any pregnancy that may be at increased risk for antepartum fetal compromise is a candidate for tests of fetal well-being performed weekly, beginning at 28 to 32 weeks. Scores of 8 or 10 points (out of 10) are considered reassuring, with retesting indicated in 4 to 7 days depending on the original indication for the testing. American College of Obstetricians and Gynecologists: Compendium of selected publications, Atlanta, 2012, American College of Obstetricians and Gynecologists. American College of Obstetricians and Gynecologists: Screening for fetal aneuploidy. The development of an ectopic pregnancy is a potentially serious threat to the general and reproductive health of a woman. The objective of this chapter is to provide an overview of the epidemiology, diagnosis, and contemporary management of ectopic pregnancy. The focus is on ectopic pregnancies that implant in the fallopian tube, which represent greater than 95% of all ectopic pregnancies. The current incidence of ectopic pregnancy is difficult to calculate accurately because of the lack of tracking in both the hospital and outpatient settings, but recent studies estimate that over the last 25 years, it has increased sixfold. This rise may be due to enhanced diagnostic capabilities, increased incidence of sexually transmitted infections and other risk factors, expanded use of infertility treatments, and heightened awareness of health professionals. However, the ectopic-related mortality rate is declining despite the increase in incidence. Between 1980 and 2007, 876 deaths were attributed to ectopic pregnancy, which represented a 56. Normal embryo transport can be disrupted by damage to the structural integrity of the mucosal portion of the fallopian tube. Intratubal scarring secondary to infection or trauma could lead to trapping of a conceptus within intratubal adhesions or diverticula. For the patient to make an informed choice, a shared decision-making model can be used that reviews the risks and benefits of both approaches and considers the clinical features of the ectopic pregnancy, stability of the patient, future fertility plans, and additional patient characteristics that would preclude one approach or the other. Uterine aspiration can be considered to confirm the diagnosis of early pregnancy loss or ectopic pregnancy based on the presence or absence of chorionic villi. Despite vast improvements in the clinical care of women with ectopic pregnancy over recent years, diagnostic challenges and therapeutic controversies regarding this condition still exist. Ectopic pregnancy is the leading cause of maternal mortality in the first trimester of pregnancy in the United States, and there should be continued high suspicion for at risk patients. Pathophysiology Damage to the fallopian tube and fallopian tube dysfunction are the primary factors associated with development of ectopic pregnancy. Alteration of the hormonally mediated events leading to implantation-as sometimes occurs in treatments for infertility- offers another mechanism for consideration. A change in the estrogen-to-progesterone ratio could theoretically affect smooth muscle activity in the fallopian tube, immobilizing ciliary activity. Risk Factors Half of all women with ectopic pregnancy will not report any known risk factors; therefore the absence of risk factors should not decrease clinical suspicion. However, identification of clinical and historical risk factors for ectopic pregnancy could aid in early diagnosis. Major historical risk factors include pain or moderate-tosevere vaginal bleeding at presentation. Prior nontubal pelvic surgery, past intrauterine device use, and cervical infection at presentation with chlamydia or gonorrhea do not contribute increased risk. The pseudogestational sac likely represents bleeding into the endometrial cavity by the decidual cast. The demonstration of an adnexal gestational sac with a fetal pole and cardiac activity is the most specific but least sensitive sign of ectopic pregnancy, occurring in only 10% to 17% of cases. Adnexal rings (fluid sacs with thick echogenic rings) that have a yolk sac or nonliving embryo are accepted as specific signs of ectopic pregnancy and are visualized in ectopic pregnancies 33% to 50% of the time. The only exception to the rule for scenario 2 would be if a multiple gestation had been conceived. The challenge for the clinician is to then determine whether the pregnancy is an abnormal intrauterine pregnancy or an ectopic pregnancy. Office uterine vacuum aspiration or dilation and curettage in the operating room can help confirm the diagnosis of early pregnancy loss or ectopic pregnancy based on the presence or absence of chorionic villi. The Ectopic Pregnancy Although some patients present acutely with a ruptured ectopic pregnancy and hemoperitoneum, the vast majority (up to 80%) of ectopic pregnancies are diagnosed in stable women who can be managed in the outpatient setting. Therefore reproductive-age women who present with symptoms of vaginal bleeding or abdominal discomfort need to be tested for pregnancy. This is a transient state known as "pregnancy of unknown location," and serial monitoring is needed to establish a definitive diagnosis. Previous data showed that approximately 99% of viable intrauterine pregnancies are associated with a! There is debate in the literature on whether uterine aspiration is needed before methotrexate is given to treat ectopic pregnancy. Empiric treatment of suspected ectopic pregnancy without the performance of uterine vacuum aspiration or dilation and curettage could result in inappropriate treatment of up to 40% of women. Performing uterine aspiration could delay treatment of an ectopic pregnancy; however, the risk of tubal rupture for these women is low (1. With respect to future fertility, much of the published data supports higher odds of intrauterine conception after salpingostomy compared with salpingectomy; some studies, however, suggest no difference in the odds of intrauterine pregnancy on the basis of the method of ectopic surgery. The most important determinant of normal conception after surgical treatment is the presence of a healthy contralateral fallopian tube. The odds of recurrent ectopic pregnancy appear to be higher in women after conservative rather than radical surgical treatment. Medical Management Treatment and Therapeutic Monitoring Surgery has long been the mainstay of treatment for ectopic pregnancy, but medical management is a widely used alternative. Both are safe and effective treatment options for women who are clinically stable. The choice of any treatment depends on factors such as clinical presentation, the risks of either surgery or medical management to the patient, and future fertility plans. Most women with ectopic pregnancy who are stable can be safely treated with laparoscopy. For a woman with an unruptured ectopic pregnancy, surgical options include tube-sparing salpingostomy or removal of the fallopian tube (salpingectomy). Ideal candidates for linear salpingostomy include patients who have an ectopic pregnancy in the ampulla or infundibulum of the fallopian tube. Prophylactic methotrexate has been proposed as a means of reducing the odds of a persistent ectopic pregnancy following conservative surgery. Salpingectomy is reserved for patients with isthmic ectopic pregnancies, tubal rupture, or an ipsilateral recurrent ectopic pregnancy. Salpingectomy is more appropriate for isthmic ectopic pregnancies because the narrowness of the isthmic lumen of the fallopian tube can predispose to tubal obstruction and scarring after salpingostomy. Women who have completed childbearing might be better candidates for salpingectomy than salpingostomy. Although medical treatment of ectopic pregnancy is an appealing option for many patients, certain absolute contraindications exist to the use of the drug and are listed in Table 1. Without the ability to monitor response to medication and provide additional doses if deemed appropriate, opportunities to prevent ectopic rupture could be missed. In some cases, medication failure presents as tubal rupture requiring emergent surgery. Three methotrexate treatment regimens exist: single-dose, twodose, and multidose regimens (Table 2). These designations refer more to the number of intended doses in the protocol rather than the actual number or doses received by all patients. Although each regimen has demonstrated efficacy, only one small, randomized trial of comparative efficacy exists in which no significant difference between protocols was observed. Serious side effects such as alopecia and neutropenia can occur but are extremely rare. The most critical predictors of fertility after ectopic pregnancy treated by any conservative means are the condition of the contralateral fallopian tube and the presence of additional ectopic risk factors. Of note, the meta-analysis demonstrated that patients designated to receive single-dose therapy often received more than one dose and that patients getting multidose therapy often required fewer than four doses to be cured. Abdominal pain is common early in treatment and is of concern as a possible indicator of tubal rupture. Additional potential side effects include nausea, vomiting, diarrhea, gastritis, stomatitis, and liver transaminitis. Delivery time is based on severity of maternal symptoms and estimated gestational age of the fetus. Epidemiology Hypertensive disorders complicate nearly 10% of pregnancies (Box 1) and their incidence is increasing. Some of these outcomes can be prevented or improved on through implementation of the updated recommendations in clinical practice. Impaired liver function Pulmonary edema Cerebral or visual symptoms Pathophysiology 1162 the precise mechanism for the development of preeclampsia is unknown. In addition, there appears to be a heritable component, and oxidative stress and abnormal placental implantation can further increase the risk of developing the disease. Supplementation with vitamin C1 or E1 is not recommended in the prevention of preeclampsia. Supplementation of calcium1 in women with preeclampsia is only indicated in those who are calciumdeficient. Isolated hypertensive disease diagnosed prior to 20 weeks of gestation is classified as chronic hypertension. Preeclampsia is a hypertensive disorder that is multisystemic in nature and is specific to pregnancy. Traditionally, diagnosis of preeclampsia has been based on new onset hypertension and the presence of proteinuria. The use of dipstick quantification of proteinuria is discouraged unless no other method is available. Urinary protein levels are not correlated with outcome severity and are not themselves considered a severe feature. There are some women who present with hypertension and signs of systemic disease in the absence of proteinuria. In addition to seizure and maternal end-organ damage, complications from preeclampsia include intrauterine growth restriction, placental abruption, and fetal demise. It is essential to avoid overtreatment, to prevent adverse fetal outcomes from decreased perfusion. Women with chronic hypertension should also be monitored with serial ultrasound after fetal viability. Gestational hypertension is managed with expectant monitoring and delivery at 37 weeks. Preeclampsia should be managed similarly to gestational hypertension, with the addition of regular sonograms for fetal growth, and twice-weekly fetal nonstress testing. Delivery should occur at 37 weeks, and should occur at 34 weeks if patient develops severe features. If severe features are noted prior to fetal viability, delivery should occur immediately. Inpatient management for 72 h postpartum is recommended for women with gestational hypertension or preeclampsia. Blood pressure levels decrease in most women, but if blood pressure remains >150/100 on two occasions 4 h apart, an antihypertensive regimen should be started. Oral nifedipine or labetalol, and intravenous labetalol or hydralazine (Apresoline) are commonly used agents.
Anticholinergic drugs and plants are not routinely included on screens for substances of abuse symptoms untreated hiv infection buy acivir pills 200 mg with mastercard. Management For patients in respiratory failure hiv infection diagnosis acivir pills 200mg mastercard, intubation and assisted ventilation should be instituted hiv zero infection buy acivir pills 200mg overnight delivery. If bowel sounds are present for up to 1 hour after ingestion hiv infection stories order acivir pills 200 mg visa, activated charcoal can be given hiv infection in south africa generic acivir pills 200mg online. Seizures can be controlled with benzodiazepines (diazepam [Valium] or lorazepam [Ativan]) antiviral substance buy acivir pills mastercard. The administration of physostigmine (Antilirium) is not routine and is reserved for life-threatening anticholinergic effects that are refractory to conventional treatments. It should be administered with adequate monitoring and resuscitative equipment available. The use of physostigmine should be avoided if a tricyclic antidepressant is present because of increased toxicity. Urinary retention should be relieved by catheterization to avoid reabsorption of the drug and additional toxicity. Supraventricular tachycardia should be treated only if the patient is hemodynamically unstable. Torsades de pointes, especially when associated with terfenadine and astemizole ingestion, has been treated with magnesium sulfate 4 g or 40 mL 10% solution intravenously over 10 to 20 minutes and countershock if the patient fails to respond. Disposition observed on a monitored unit until the symptoms resolve, then observed for a short time (3 to 4 hours) after resolution for relapse. Asymptomatic adults who acutely ingest more than twice the maximum adult daily dose should be monitored for a minimum of 6 hours. All symptomatic patients should be monitored for as long as there are symptoms present. Barbiturates Barbiturates have been used as sedatives, anesthetic agents, and anticonvulsants, but their use is declining as safer, more effective drugs become available. Toxic Dose the shorter-acting barbiturates (including the intermediate-acting agents) and their hypnotic doses are as follows: amobarbital (Amytal), 100 to 200 mg; aprobarbital (Alurate), 50 to 100 mg; butabarbital (Butisol), 50 to 100 mg; butalbital, 100 to 200 mg; Antihistamine H1 Antagonists. Symptomatic patients should be pentobarbital (Nembutal), 100 to 200 mg; secobarbital (Seconal), 100 to 200 mg. They cause toxicity at lower doses than long-acting barbiturates and have a minimum toxic dose of 6 mg/kg; the fatal adult dose is 3 to 6 g. The long-acting barbiturates and their doses include mephobarbital (Mebaral), 50 to 100 mg, and phenobarbital, 100 to 200 mg. Their minimum toxic dose is greater than 10 mg/kg, and the fatal adult dose is 6 to 10 g. A general rule is that an amount five times the hypnotic dose is toxic and an amount 10 times the hypnotic dose is potentially fatal. Methohexital and thiopental are ultrashort-acting parenteral preparations and are not discussed. Short-acting barbiturates are highly lipid-soluble, penetrate the brain readily, and have shorter elimination times. Long-acting agents have longer elimination times and can be used as anticonvulsants. Manifestations Mild intoxication resembles alcohol intoxication and includes ataxia, slurred speech, and depressed cognition. Severe intoxication causes slow respirations, coma, and loss of reflexes (except pupillary light reflex). Other manifestations include hypotension (vasodilation), hypothermia, hypoglycemia, and death by respiratory arrest. Laboratory Investigations Most barbiturates are detected on routine drug screens and can be measured in most hospital laboratories. The minimum toxic plasma levels are greater than 10 g/mL for short-acting barbiturates and greater than 40 g/dL for long-acting agents. Fatal levels are 30 g/mL for short-acting barbiturates and 80 to 150 g/mL for long-acting agents. Both short-acting and long-acting agents can be detected in urine 24 to 72 hours after ingestion, and long-acting agents can be detected up to 7 days. Intensive supportive care including intubation and assisted ventilation should dominate the management. All stuporous and comatose patients should have glucose (for hypoglycemia), thiamine (if chronically alcoholic), and naloxone (Narcan) (in case of an opioid ingestion) intravenously and should be admitted to the intensive care unit. Emesis should be avoided especially in cases of ingestion of the shorter-acting barbiturates. Vasopressors may be necessary to correct severe hypotension, and hemodynamic monitoring may be needed. Both procedures may be effective in patients with both long-acting and short-acting barbiturate ingestion. If the patient does not respond to supportive measures or if the phenobarbital plasma concentration is greater than 150 g/mL, both procedures may be tried to shorten the half-life. Awake and oriented patients with an overdose of short-acting agents should be observed for at least 6 asymptomatic hours; overdose of long-acting agents warrants observation for at least 12 asymptomatic hours because of the potential for delayed absorption. In the case of an intentional overdose, psychiatric clearance is needed before the patient can be discharged. Chronic use can lead to tolerance, physical dependency, and withdrawal and necessitates follow-up. Benzodiazepines Benzodiazepines are used as anxiolytics, sedatives, and relaxants. Laboratory Investigations Most benzodiazepines can be detected in urine drug screens. Some of the immunoassay urinary screens cannot detect all of the new benzodiazepines currently available. Situations in which benzodiazepines may not be detected include ingestion of a low dose. Some immunoassay methods can produce a falsepositive finding for the benzodiazepines when nonsteroidal antiinflammatory drugs (tolmetin [Tolectin], naproxen [Aleve], etodolac [Lodine], and fenoprofen [Nalfon]) are used. In cases in which "date rape" drugs such as flunitrazepam are suspected, a police crime or reference laboratory should be consulted for testing. Activated charcoal can be useful only if given early before the peak time of absorption occurs. Supportive treatment should be instituted but rarely requires intubation or assisted ventilation. It reverses the sedative effects of benzodiazepines, zolpidem (Ambien), and endogenous benzodiazepines associated with hepatic encephalopathy. The manufacturer advises that flumazenil be used with caution in cases of overdose with possible benzodiazepine dependency (because it can precipitate life-threatening withdrawal), if cyclic antidepressant use is suspected, or if a patient has a known seizure disorder. Disposition If the patient is comatose, he or she must be admitted to the intensive care unit. If the overdose was intentional, psychiatric clearance is needed before the patient can be discharged. Cardiac membrane depressive effect (quinidine-like) occurs in cases of overdose but not at therapeutic doses. Toxic Mechanism -Blockers compete with the catecholamines for receptor sites and block receptor action in the bronchi, the vascular smooth muscle, and the myocardium. Toxic Dose Ingestions of greater than twice the maximum recommended daily therapeutic dose are considered toxic (see Table 12). Flunitrazepam (Rohypnol; street name "roofies") is a longacting benzodiazepine agonist sold by prescription in more than 60 countries worldwide, but it is not legally available in the United States. Toxic Dose the long-acting benzodiazepines (half-life >24 hours) and their maximum therapeutic doses are as follows: chlordiazepoxide (Librium), 50 mg; clorazepate (Tranxene), 30 mg; clonazepam (Klonopin), 20 mg; diazepam (Valium), 10 mg in adults or 0. The short-acting benzodiazepines (half-life 10 to 24 hours) and their doses include the following: alprazolam (Xanax), 0. The ultrashort-acting benzodiazepines (half-life <10 hours) are more toxic and include temazepam (Restoril), 30 mg; triazolam (Halcion), 0. In cases of overdose of short- and long-acting agents, 10 to 20 times the therapeutic dose (>1500 mg diazepam or 2000 mg chlordiazepoxide) have been ingested with resulting mild coma but without respiratory depression. Fatalities are rare, and most patients recover within 24 to 36 hours after overdose. Asymptomatic unintentional overdoses of less than five times the therapeutic dose can be seen. Ultrashort-acting agents have produced respiratory arrest and coma within 1 hour after ingestion of 5 mg of triazolam (Halcion) and death with ingestion of as little as 10 mg. Midazolam (Versed) and diazepam (Valium) by rapid intravenous injection have produced respiratory arrest. The onset of action with sustained-release preparations may be delayed to 6 hours and the peak to 12 to 16 hours. Metabolism Atenolol (Tenormin), nadolol (Corgard), and sotalol (Betapace) have enterohepatic recirculation. The duration of action for regular-acting agents is 4 to 6 hours, but in cases of overdose it may be 24 to 48 hours. The regular preparation with the longest half-life is nadolol, at 12 to 24 hours, and the one with the shortest half-life is esmolol, at 5 to 10 minutes. Bradycardia and hypotension are the major cardiac symptoms and may lead to cardiogenic shock. Bronchospasm may occur in patients with reactive airway disease with any -blocker because the selectivity is lost in overdose. Other manifestations include hypoglycemia (because -blockers block catecholamine counter-regulatory mechanisms) and hyperkalemia. Laboratory Investigations Measurements of blood levels are not readily available or useful. Gastrointestinal decontamination can be undertaken initially with activated charcoal up to 1 hour after ingestion. Whole-bowel irrigation can be considered in cases of large overdoses with sustainedrelease preparations, but there are no studies evaluating the efficacy of intervention. If there are cardiovascular disturbances, a cardiac consultation should be obtained. Hypotension is treated with fluids initially, although it usually does not respond. Bradycardia in asymptomatic, hemodynamically stable patients 1293 Medical Toxicology 1294 requires no therapy. If the patient is unstable (has hypotension or a high-degree atrioventricular block), atropine 0. Torsades de pointes (associated with sotalol) may respond to magnesium sulfate and overdrive pacing. Hypotension and myocardial depression are managed by correction of dysrhythmias, Trendelenburg position, fluids, glucagon, or amrinone (Inocor), or a combination of these. Hemodynamic monitoring with a Swan-Ganz catheter or arterial line may be necessary to manage fluid therapy. It works through adenyl cyclase and bypasses catecholamine receptors; therefore, it is not affected by -blockers. It is given as an intravenous bolus of 5 to 10 mg3 over 1 minute and followed by a continuous infusion of 1 to 5 mg/h (in children, 0. In large doses and in infusion therapy D5W, sterile water, or saline should be used as a dilutant to reconstitute glucagon in place of the 0. Lifethreatening hyperkalemia is treated with calcium (avoid if digoxin is present), bicarbonate, and glucose or insulin. Extraordinary measures such as intra-aortic balloon pump support can be instituted. Hemodialysis for cases of atenolol, acebutolol, nadolol, and sotalol (low volume distribution, low protein binding) ingestion may be helpful, particularly when there is evidence of renal failure. Prenalterol2 has successfully reversed both bradycardia and hypotension but is not currently available in the United States. If seizures or abnormal rhythm or vital signs are present, the patient should be admitted to the intensive care unit. Calcium Channel Blockers Calcium channel blockers are used in the treatment of effort angina, supraventricular tachycardia, and hypertension. Toxic Mechanism Calcium channel blockers reduce influx of calcium through the slow channels in membranes of the myocardium, the atrioventricular nodes, and the vascular smooth muscles and result in peripheral, systemic, and coronary vasodilation, impaired cardiac conduction, and depression of cardiac contractility. All calcium channel blockers have vasodilatory action, but only bepridil, diltiazem, and verapamil depress myocardial contractility and cause atrioventricular block. Toxic Dose Any ingested amount greater than the maximum daily dose has the potential of severe toxicity. The maximum oral daily doses in adults and toxic doses in children of each are as follows: amlodipine (Norvasc), 10 mg for adults and more than 0. Kinetics Onset of action of regular-release preparations varies: for verapamil it is 60 to 120 minutes, for nifedipine 20 minutes, and for diltiazem 15 minutes after ingestion. Peak effect for verapamil is 2 to 4 hours, for nifedipine 60 to 90 minutes, and for diltiazem 30 to 60 minutes, but the peak action may be delayed for 6 to 8 hours. The onset of action for sustained-release preparations is usually 4 hours but may be delayed, and peak effect is at 12 to 24 hours. Patients receiving digitalis and calcium channel blockers run the risk of digitalis toxicity, because calcium channel blockers increase digitalis levels. Manifestations Cardiac manifestations include hypotension, bradycardia, and conduction disturbances occurring 30 minutes to 5 hours after ingestion. Hyperglycemia may be present because of interference in calcium-dependent insulin release. Laboratory Investigations Specific drug levels are not readily available and are not useful. If a large dose of a sustained-release preparation was ingested, whole-bowel irrigation can be considered, but its effectiveness has not been investigated. If the patient is symptomatic, immediate cardiology consult must be obtained, because a pacemaker and hemodynamic monitoring may be needed.