Estella Whimbey, M.D.

• Associate Professor of Medicine
• University of Washington
• Associate Medical Director
• Employee Health Center
• University of Washington Medical Center
• Medical Director
• Healthcare Epidemiology and Infection Control
• University of Washington Medical
• Center/Seattle Cancer Care Alliance (inpatients)
• Seattle, Washington

History of colorectal cancer in a first-degree relative increases risk of endometrial cancer 2-fold erectile dysfunction doctors staten island priligy 60 mg fast delivery. Protection lasts for at least 10 years after discontinuation of oral contraceptive erectile dysfunction specialist buy priligy 30mg without prescription. Similar protection has been observed with long-term use (10 years) of hormone replacement therapy that includes daily progestin impotence at 33 cheap priligy 60mg with amex. Physical activity: Lack of sufficient activity (20 minutes or more of vigorous physical activity at least three times per week) has been associated with a 30% to 40% increased risk of endometrial cancer impotence from anxiety buy priligy american express. However prostate cancer erectile dysfunction statistics purchase discount priligy, this is strongly outweighed by the significantly increased risk of lung cancer and other diseases impotence causes and cures discount 60 mg priligy overnight delivery. Signs and Symptoms Abnormal uterine bleeding to include postmenopausal bleeding is the most common symptom of endometrial cancer, seen in approximately 90% of cases. Premenopausal women with prolonged and/or heavy menses or intermenstrual spotting should undergo endometrial biopsy. All postmenopausal women with uterine bleeding should be evaluated for endometrial cancer (10% of these patients will ultimately be diagnosed with the malignancy). Biopsy is also recommended for women taking estrogen therapy for menopausal symptoms who have withdrawal bleeding. Asymptomatic patients with abnormal glandular tissue on Pap smear should be evaluated for endometrial cancer. All postmenopausal women with endometrial cells on Pap smear should be evaluated for malignancy. Pap smear alone, however, is not an adequate tool for detecting endometrial malignancy. Palpable, locally advanced tumor detected on pelvic examination is suggestive of endometrial cancer. Endometrial biopsy is generally a well-tolerated outpatient procedure and has a diagnostic accuracy of 93% to 98% when compared with subsequent findings of hysterectomy or dilation and curettage (D&C). Women with postmenopausal bleeding may be initially assessed with either an endometrial biopsy or transvaginal ultrasound. When ultrasound measurement of endometrial thickness is less than or equal to 4 mm, endometrial sampling is not required because the incidence of malignancy is rare in these cases. However, if postmenopasual bleeding persists, endometrial sampling should be performed. In this setting, there is no consensus on the cutoff thickness of endometrial stripe that would indicate a need for endometrial biopsy. Most are estrogen dependent, and many have positive estrogen and progesterone receptors. These tumors tend to occur in older, thin, postmenopausal women with no source of excess estrogen, arising in the background of atrophic endometrium. Women with the serous subtype are at increased risk of developing a concurrent or subsequent breast cancer-breast cancer is diagnosed in 20% to 25% of patients with serous subtype compared to 3% with endometrioid subtype. Chest x-ray should be performed to rule out pulmonary metastasis and to evaluate the cardiorespiratory status of the patient. Additional imaging studies to include pelvic or abdominal imaging to assess myometrial invasion or cervical involvement are unnecessary if surgical staging is planned. Extrauterine Positive peritoneal cytology: Rate of disease recurrence is approximately 15%. Within this subgroup, there are additional adverse prognostic factors used to further stratify women into high- and low-intermediate risk. These include deep myometrial invasion, grade 2 or 3 histology, or the presence of lymphovascular space invasion within the cancer. Women with serous or clear cell histology are categorized as highrisk regardless of stage. Additional prognostic considerations that influence decision of adjuvant therapy include lower uterine segment involvement, positive peritoneal cytology, older age, African-American race, and molecular prognostic factors. Surgery is the cornerstone of staging and therapy for most patients with endometrial cancer. Treatment is stratified based on the risk of disease recurrence, which is determined using the stage of disease, histology of the tumor, and other pathologic factors. The risk is 3% to 5% in patients with well-differentiated superficially invasive tumors, but as high as 20% in poorly differentiated deeply invasive disease. Endometrial carcinoma: Therapy should be individualized for endometrial carcinoma using risk based on histology and stage. If no peritoneal fluid is found during surgery, peritoneal washing with normal saline should be done. High risk: surgical staging (see above) followed by adjuvant chemotherapy, which has shown a survival advantage. One randomized study of platinum-based chemotherapy in stage I uterine papillary serous carcinoma showed improvement in disease-free and overall survival. Vaginal brachytherapy: May be administered alone if patient has undergone complete surgical staging to confirm that disease is confined to the uterus. Radiation may be administered after completion of 6 cycles of chemotherapy, "sandwiched" in between 3 cycles of chemotherapy before and after radiation treatment, or concurrently. Special Considerations Low-risk, low-grade patients who still desire fertility can be managed with progestational agents such as levonorgestrel-releasing intrauterine system. Therefore, special attention should be given to appropriate patient selection and choice of surgical techniques. Pelvic surgery has an increased risk of thrombophlebitis in the pelvis and lower extremities; hence, low-dose heparin or compression stockings should be used. The subgroup of women with isolated ovarian metastasis has a relatively better prognosis. However, some believe that this represents double primary tumors rather than true metastasis from primary endometrial cancer. Five-year disease-free survival ranges between 60% and 82%, depending on histologic grade and depth of myometrial invasion. Pelvic radiation doses of 45 to 50 Gy are given in standard fractionation, with vaginal boost with cylinder or colpostats adding 30 to 35 Gy to the vaginal surface. Local Recurrence Pelvic exenteration: this method can be considered for patients with disease extending only to the bladder or rectum or for isolated central recurrence after irradiation. For isolated vaginal recurrence, irradiation may be curative if not previously administered. Distant Metastasis: Systemic Therapy Hormonal therapy produces responses in 15% to 30% of patients and is associated with survival twice as long as in nonresponders. Hormonal therapy is used for endometrioid histologies only (not for clear cell, serous, or carcinosarcoma). Hormonal therapy is preferred as first-line intervention for recurrent or metastatic endometrial cancer due to its lower toxicity profile and response rate similar to chemotherapy. Options include the following: Megestrol acetate (Megace), 160 to 320 mg daily, is the preferred initial regimen. There is no role for hormonal therapy in the adjuvant setting to treat earlystage disease. Response rates 17% to 28%; partial responses of short duration (<6 months); overall survival 9 to 12 months. Combinations may include carboplatin/paclitaxel, cisplatin/doxorubicin, cisplatin/doxorubicin/paclitaxel, carboplatin/paclitaxel, ifosfamide/paclitaxel. Paclitaxel-containing regimens may improve response and progressionfree intervals; overall survival advantages may be seen in time. Less well-studied treatment regimens have been proposed: Chemotherapy in conjunction with hormonal therapy. Trials are in progress looking at bevacizumab in combination with carboplatin and paclitaxel. Estrogen-Replacement Therapy Estrogen-replacement therapy for patients with endometrial cancer remains controversial. Post-therapy Surveillance Most recurrences are seen in the first 3 years after primary therapy (>50% of recurrences occur within 2 years and approximately 75% within 3 years of initial treatment). Up to 70% of patients with recurrent disease will report symptoms of vaginal bleeding, pain, cough, or weight loss. Genetic counseling or testing is advised in patients <50 years of age with a significant family history and/or pathologic features suggestive of Lynch syndrome. There were an estimated 265,672 deaths from uterine cervix cancer worldwide in 2012, making it the fourth most common lethal cancer in women and 10th overall. Among American women, uterine cervix cancer is the third most common cancer of the genital system, with an estimated 12,990 new cases and 4,120 deaths estimated in 2016. Papanicolaou (Pap) smear screening has lowered the incidence and mortality of invasive uterine cervix cancer by almost 75% over the past 50 years; however, nearly 85% of cases occur in less developed regions where Pap screening may not be available. Uterine cervix cancer incidence among American women continues to decline but remains disproportionately high among subpopulation (American blacks, Hispanics of any race, Asian/Pacific Islander Americans, American Indian/Alaskan Natives). In developed socioeconomic regions, the cumulative risk of uterine cervix cancer by age 75 years is 0. Women aged 21 to 29 should be screened with cervical cytology alone every 3 years. Cervical cytology should be described using the 2001 Bethesda System detailing specimen adequacy and interpretation. Interpretation is divided into nonmalignant findings and epithelial cell abnormalities including squamous and glandular abnormalities. Nevertheless, the rate of progression of mild dysplasia to severe dysplasia is 1% per year; the rate of progression of moderate dysplasia to severe dysplasia is 16% within 2 years and 25% within 5 years. Untreated carcinoma in situ has a 30% probability of progression to invasive cancer over a 30-year observation period. Vaginal discharge (serosanguinous or yellowish, sometimes foul smelling) may represent a more advanced lesion. Pain in the lumbosacral or gluteal area may suggest hydronephrosis caused by tumor, or tumor extension to lumbar nerve roots. Persistent, unilateral, or bilateral leg edema may indicate lymphatic and venous blockage caused by extensive pelvic sidewall nodal or tissue disease. The most frequent examination abnormalities include visible cervical lesions or abnormalities on bimanual pelvic examination. About 15% of adenocarcinomas have no visible lesion because the carcinoma is within the endocervical canal. Seventy-five percent to 80% of uterine cervix cancers are of squamous cell histology; the remaining 20% to 25% are mostly adenocarcinomas or adenosquamous carcinomas. Stage is the most important prognostic factor, followed by lymph node involvement. Lymphatic dissemination most commonly involves pelvic lymph nodes first and then para-aortic lymph nodes. Vascular spread is late in the disease process, and metastases occur in lung, liver, and bone. Noninvasive lesions can be treated with electrosurgical excision, cryotherapy, laser excision or ablation, surgical conization, or other surgical procedures. If preservation of fertility is desired, conization with negative margins followed by surveillance is reasonable. Larger tumors are usually only treated with radiochemotherapy (or, radiation alone in special circumstances). Based on these data, the National Cancer Institute issued a clinical alert informing cancer care providers that a strong consideration should be given to adding cisplatin-based chemotherapy to radiotherapy in the treatment of invasive uterine cervix cancer. For those who wish to preserve fertility, a conization with negative margins, followed by observation is adequate therapy. However, if margins are positive, options include radical trachelectomy or repeat cone biopsy. Para-aortic lymph node dissection is reserved for patients with known or suspected nodal disease. Laparoscopic and robotic approaches are associated with shortened recovery time, decreased hospital stay, and less blood loss. Para-aortic lymph node sampling may be indicated in patients with positive pelvic nodes, clinically enlarged nodes, or patients with largevolume disease. If definitive radiotherapy is chosen over radical hysterectomy, concurrent cisplatin-based chemotherapy should be administered. For patients at high risk for lymph nodes involvement, the radiation field should also cover common iliac lymph nodes. If common iliac or para-aortic lymph node involvement is clinically suspected, extended-field radiation that raises the superior radiation portal boundary up at least to the level of renal vessels is recommended. Both high-dose brachytherapy (isotope 192Iridium; rate 200 to 300 cGy per hour) and low-dose brachytherapy (isotope 137Cesium; rate 40 to 70 cGy per hour) are used. Determining maximum effective dose to the primary tumor, as well as to the bladder and rectum, is of primary importance. Anatomically, it correlates with the boundary between the lateral uterine cervix and the medial edge of parametrial tissue, an anatomic point where the ureter and uterine artery cross.

Impact of periodontal therapy on general health: Evidence from insurance data for five systemic conditions erectile dysfunction caused by sleep apnea generic 30mg priligy mastercard. The relationship between periodontal interventions and healthcare costs and utilization: Evidence from an integrated dental erectile dysfunction over 70 order cheap priligy on line, medical erectile dysfunction more causes risk factors priligy 30mg with amex, and pharmacy commercial claims database impotence zargan proven priligy 30 mg. Person-centric clinical trials: Defining the N-of-1 clinical trial utilizing a practice-based translational network herbal erectile dysfunction pills canada safe 90mg priligy. Dental homes for older Americans: the Santa Fe Group call for removal of the dental exclusion in Medicare impotence yahoo purchase priligy. The Santa Fe Group strategy: How Medicare can integrate health and oral care for older Americans. Community Statement on Medicare Coverage for Medically Necessary Oral and Dental Health Therapies. Misch, dds, mds A primary diagnostic consideration of dental implant placement in the maxilla is the bone volume of the residual ridge. In the posterior maxilla, the maxillary sinus often limits the available bone for implant placement. The clinician can avoid the sinus by either selecting a shorter implant size or tilting the implant position away from the sinus cavity. Another option is to elevate the sinus mucosa to establish a new sinus floor at a more superior level. The goals of the sinus elevation procedure are to augment bone height in the posterior maxilla for dental implant placement, promote the development of a bone-to-implant interface contact, and enable long-term survival of the implants under prosthetic loading. This article discusses various strategies for managing the sinus floor, including surgical approaches, graft materials, and future directions. Indications for Sinus Bone Grafting During growth of the facial skeleton, the sinus cavities expand in volume. The floor of the maxillary sinus is often in close approximation to the posterior tooth roots. When posterior teeth are lost, the sinus further expands, reducing the amount of residual bone. Following extraction of the posterior teeth, there is also a loss of facial bone, resulting in medial resorption of the maxillary ridge. These conditions can compromise the placement of dental implants for prosthetic support. The management of maxillary atrophy and sinus pneumatization for dental implant placement has evolved over the years. When sinus bone grafting was first developed, clinicians favored the use of longer dental implants. This was thought necessary for optimal biomechanical loading of the implant and prosthetic support. In addition, shorter machine-surfaced implants (< 10 mm) showed lower survival rates in the posterior maxilla. An early classification protocol recommended lateral window sinus bone grafting when there was 8 mm or less of bone height below the sinus floor for placement of the maximum implant length (> 15 mm). Many studies have even shown that the survival of short implants is the same as longer implants placed into grafted sinuses. However, short implants do have a higher risk of failure during the early healing period, which may be due to their reduced stability in softer bone. This reduces the volume of bone grafting that is needed for implant placement and may even avoid the need for sinus augmentation. It may also allow the surgeon to consider an osteotome sinus floor elevation for short implant placement rather than using a lateral window technique. Although there is no definitive bone dimension needed before considering sinus bone grafting, there is a lack of substantive long-term data on shorter implants (< 8 mm) in the posterior maxilla. The decision to place short implants versus sinus grafting for longer implants should be based on long-term studies, implant design, sinus pathology, surgical experience, and patient preferences. Autogenous bone grafts heal faster, so using autograft as the sole material or combining it with bone substitutes can shorten the healing time requirements to 4 to 6 months. A systematic review revealed no significant differences in the survival of implants placed simultaneous with grafting or after graft healing. Sinus Grafting Techniques Simultaneous Versus Delayed Implant Placement the decision to place dental implants simultaneous with sinus bone grafting or staging placement after graft healing depends on several factors: the quantity and quality of bone below the sinus, implant design, clinical conditions, and experience of the surgeon. The advantages of simultaneous grafting and implant placement are decreased morbidity, lower costs, and shorter treatment duration. The edentulous posterior maxilla typically has a thin outer cortex with softer quality trabecular bone, and the sinus floor is a thin cortical shell. As such, the minimum bone height needed to place an implant simultaneous with grafting is approximately 4 to 5 mm. Grafting for simultaneous implant placement may be accomplished along the sinus floor via a lateral window or transcrestal approach. Another option is to place implants without any bone graft material, allowing the implant apices to tent the sinus membrane so blood clot or platelet concentrate alone can be used to provide enough matrix for bone ingrowth. When inadequate bone volume is present below the sinus for implant support, the sinus floor can be augmented. Conventional radiographs, such as periapical and panoramic films, are useful for preliminary screening of potential implant sites. Cone beam computed tomography can better assess the available bone and further evaluate sinus health and morphology. Cross-sectional images are useful to evaluate the ridge width, bone quality, and sinus floor. The buccopalatal distance of the sinus can influence the amount of graft material needed for augmentation and healing time requirements. The surgeon should also evaluate the residual ridge for facial bone loss and medial resorption following tooth loss. This may necessitate concomitant horizontal bone augmentation for ideal implant placement. Lateral window approach the lateral window approach is performed in the posterior maxilla by creating an osteotomy over the lateral sinus wall and leaving the sinus mucosa intact. This approach requires vertical releasing incisions with greater flap reflection and retraction than a transcrestal sinus floor elevation. In addition, vessels within the lateral sinus wall may be disrupted during preparation of the bony window, causing intraoperative bleeding. There may also be a greater risk of sinus mucosa perforation using this approach compared with a transcrestal elevation. Serious infections are rare but can occur with this more invasive surgical approach. The main advantages of using a lateral window approach are superior access, visibility of the mucosal elevation, and direct access to the sinus floor. This allows for placement of larger volumes of graft material and greater vertical bone augmentation. For this reason, it is the preferred technique for managing the pneumatized sinus with minimal residual bone below the sinus floor (0 to 5 mm). It would also be the preferred approach if additional simultaneous horizontal or vertical ridge augmentation of the posterior maxilla were needed. The posterior maxilla resorbs medially following tooth loss, and this pattern of bone loss may result in an unfavorable ridge relationship with the opposing mandibular dentition. If there is adequate residual bone height, implants may be placed simultaneous with the graft. The lateral window technique may also be useful in cases where sinus bone septa would complicate an internal osteotome lift. In this instance, two windows can be created on each side of the septa and the sinus mucosa can be elevated around and over the bony projection. A lateral window approach also allows for the removal of sinus pathology in conjunction with sinus grafting. A systematic review on the lateral window sinus grafting technique including 59 articles and 13,162 implants found an overall implant survival of 93. The use of a membrane to cover the window over the graft may also have a positive influence on implant survival. The use of a rough-surfaced implant and membrane coverage over the graft was found to improve implant survival to 98. Transcrestal approach the transcrestal approach for sinus augmentation involves creating an osteotomy through the ridge crest of the posterior maxilla. The thin layer of remaining bone can be gently upfractured and elevated with an osteotome or carefully reduced with a diamond bur or piezoelectric tip. Reverse-rotating osseodensification burs are another method to create the transcrestal osteotomy without disrupting the sinus mucosa (see chapter 10). This indirect method requires less flap manipulation, so it is less invasive than the lateral window technique. The space between the implant apex and sinus mucosa fills with blood clot that heals into bone (see chapter 7). The matrix of fibrin, embedded with platelet and leukocyte cytokines, can act as a cushion to protect the sinus membrane and facilitate bone healing. Larger amounts of bone augmentation can be achieved using particulate bone graft materials. The graft particles are gently compressed and elevated superiorly with an osteotome. Grafting via the indirect method is less invasive but has the disadvantage that detection and management of sinus mucosa perforations is limited. Disruption of the sinus mucosa can occur during drilling of the osteotomy, mucosal elevation, or graft and implant placement. The presence of air bubbles appearing through the osteotomy indicates a loss of mucosal integrity. Benign paroxysmal positional vertigo has been documented as an infrequent but unpleasant complication of the osteotome technique. An endoscopic examination found the increase in height by an osteotome technique alone should be limited to approximately 3 mm. Experienced surgeons proficient in the transcrestal technique may manage cases with minimal available bone. Devices have also been developed to assist transcrestal grafting using hydraulic pressure or a balloon catheter to elevate the sinus mucosa. A systematic review on the transcrestal osteotome technique including 34 studies and 3,119 implants found an overall implant survival of 96. Transcrestal sinus floor elevation was most predictable when the residual alveolar bone height was greater than 5 mm. Shorter implants (< 8 mm) demonstrated significantly lower cumulative survival rates than longer implants. The conference unanimously agreed that the sinus graft was an efficacious procedure. The various materials used for grafting all seemed to perform acceptably, and it was not possible to state with certainty that one material was better than another. One limitation in evaluating the graft materials is that the residual bone below the sinus floor is often not reported. Dental implant survival may be a function of residual native bone supporting the implant rather than grafted bone. The literature on sinus graft success is often evaluated by secondary outcomes, such as dental implant survival or histologic studies. In addition, patients may suffer cluster implant failures due to factors unrelated to the graft material. This section evaluates studies on sinus grafting and discusses the use of different choices for graft materials. Autogenous bone Literature review the interpretation of the results with using autogenous bone for sinus grafting has been confusing and controversial. Many clinicians have incorrectly concluded that the use of autograft is associated with a lower implant survival or that bone substitutes provide better results. The 1996 Sinus Consensus Conference issued a consensus statement that autogenous bone is appropriate for sinus grafting. A 2004 systematic review on sinus bone grafting by Del Fabbro et al14 concluded that bone substitutes are as effective as autogenous bone. Four years later, the same group published an updated review with additional data. However, in deriving this conclusion they combined the survival of both machine-surfaced and rough-surfaced implants in grafted sinuses.

In addition erectile dysfunction what to do order priligy with american express, associations for certain cancers remain positive among never-smokers impotence drugs safe 60mg priligy, arguing against confounding by smoking erectile dysfunction with new partner cheap priligy 30mg amex. Dental practitioners should be able to inform patients that there is a possibility that periodontal disease increases the risk of cancer erectile dysfunction causes cures discount priligy online american express, particularly oral diabetes and erectile dysfunction relationship safe 90 mg priligy, lung erectile dysfunction medicine in homeopathy buy priligy 90 mg low cost, colorectal, and pancreatic cancers, but it is too early to know if periodontal treatment can reduce the risk of these cancers. Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States. Environmental and heritable factors in the etiology of oral diseases-A population-based study of Swedish twins. Genome-wide association study of biologically informed periodontal complex traits offers novel insights into the genetic basis of periodontal disease. An exploration of shared genetic risk factors between periodontal disease and cancers: A prospective co-twin study. Life in the human stomach: Persistence strategies of the bacterial pathogen Helicobacter pylori. Exploring the link between microorganisms and oral cancer: A systematic review of the literature. Collateral damage: Insights into bacterial mechanisms that predispose host cells to cancer. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/-catenin signaling via its FadA adhesin. Genetic diversity in the oral pathogen Porphyromonas gingivalis: Molecular mechanisms and biological consequences. Noncanonical dendritic cell differentiation and survival driven by a bacteremic pathogen. Secondary lymphoid organ homing phenotype of human myeloid dendritic cells disrupted by an intracellular oral pathogen. Phenotype and function of myeloid-derived suppressor cells induced by Porphyromonas gingivalis infection. Periodontal disease, tooth loss, and cancer risk in male health professionals: A prospective cohort study. Periodontal disease severity and cancer risk in postmenopausal women: the Buffalo OsteoPerio Study. Periodontitis and cancer mortality: Register-based cohort study of 68,273 adults in 10-year follow-up. A population-based study on the associations between chronic periodontitis and the risk of cancer. Periodontal disease and risk of all cancers among male never smokers: An updated analysis of the Health Professionals Follow-up Study. Chronic periodontitis and its possible association with oral squamous cell carcinoma-A retrospective case control study. Marginal periodontium as a potential reservoir of human papillomavirus in oral mucosa. Association between tooth loss and orodigestive cancer mortality in an 80-year-old community-dwelling Japanese population: A 12-year prospective study. Associations between tooth loss and mortality patterns in the Glasgow Alumni Cohort. Risk of colorectal cancer in patients with periodontal disease severity: A nationwide, population-based cohort study. Investigating the association between periodontal disease and risk of pancreatic cancer. Periodontal disease, Porphyromonas gingivalis serum antibody levels and orodigestive cancer mortality. Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study. Human oral microbiome and prospective risk for pancreatic cancer: A population-based nested case-control study. Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer. Trends in the prevalence of periodontitis in Taiwan from 1997 to 2013: A nationwide population-based retrospective study. However, even a banal-appearing lesion may be a manifestation of systemic disease or side effect of treatment for systemic disease. Moreover, the oral signs may be the first presentation of a systemic disorder, and the dentist is in a unique position to facilitate an early diagnosis. Early diagnosis and management can often diminish the morbidity associated with a systemic disease, improve well-being, and reduce health care costs. This article presents eight common oral conditions (Box 12-1) that are encountered in routine general dental practice. The differences in history, clinical findings, and diagnostic tests that may help distinguish between each of them are also presented. Oral Ulcers An ulcer is a loss of epithelium over an area of the mucosa covered by a yellow or whitish-gray fibrin pseudomembrane. However, oral ulcers associated with systemic diseases, use of some medications, infections in immunocompromised patients, vesiculobullous diseases, and immune-mediated diseases such as erythema multiforme may resemble idiopathic aphthous ulcers. Traumatic ulcer Traumatic ulcerations are caused by sharp or broken teeth, rough fillings, acute biting of the mucosa, and friction from ill-fitting dentures. As such, the side of the tongue, buccal mucosa, and lower lip are the most frequently affected sites, and removal of traumatic factors leads to resolution. Biopsy, usually performed to rule out other conditions (such as bullosing disorders), shows an ulcer with nonspecific acute and chronic inflammation. Treatment, whether idiopathic or related to systemic disease, depends on the severity and frequency of the lesions and centers around pain control, definitive treatment of the ulcers, and reducing the frequency of outbreaks. Dry area and apply to affected site three to four times a day (on gauze if appropriate). Dispense 300 mL; swish 5 mL for 3 to 5 min (timed) and spit out three to four times a day. Viscous lidocaine may be mixed in equal volume with diphenhydramine, aluminum/magnesium, and bismuth subsalicylate. The same topical Oral Ulcers management strategies are used for ulcers associated with other disorders. Aphthous-like lesions may occur in patients deficient in folic acid, iron, or vitamins B1, B2, B6, or B12; these are readily diagnosed with a blood test, and ulcers typically resolve or improve with repletion, although not always. Inflammatory bowel diseases such as Crohn disease and ulcerative colitis often lead to oral ulcers. Patients experience abdominal pain, diarrhea, fever, fatigue, weight loss, and anemia, and these can be elicited by a careful history, although oral findings may precede systemic symptoms. Crohn disease is a granulomatous inflammatory disorder of unknown etiology, although genetic, immunologic, environmental, microbial, dietary, and vascular factors have been implicated. It affects the ileum and large bowel in more than 90% of patients, although any part of the gastrointestinal tract may be affected. In addition to aphtheiform ulcers, patients with ulcerative colitis may present with pustular and ulcerative eruptions in the oral cavity referred to as pyostomatitis vegetans. Gluten-sensitive enteropathy (also known as celiac disease or celiac sprue) is an autoimmune disease of the small intestines caused by a hypersensitivity reaction to gliadin, a gluten protein. A specific association was found with chromosome 15q26, chromosome 5q, and possibly 11q. Aphthous-like ulcers are seen in 3% to 61% of patients, and dental enamel defects have been reported. Because of malabsorption after iliectomy, patients may develop aphthous-like ulcers from vitamin B12 deficiency. It is characterized by aphthous-like ulcers, genital ulcers, ocular lesions (especially anterior uveitis), and skin lesions (such as erythema nodosum). Cardiovascular, musculoskeletal, gastrointestinal, and neurologic symptoms are variably present. Onset is usually during the third and fourth decade of life, and it is more prevalent in individuals from Turkey, Japan, the Middle East, and other Asian countries. Cyclic neutropenia is a rare inherited condition due to mutations in the gene for neutrophil elastase. These patients usually have a circulating neutrophil count that fluctuates and severe neutropenia occurring every 3 weeks and lasting for 3 to 5 days. During these periods, patients are susceptible to bacterial infections and may report a history of recurrent fever, lymph node enlargement, malaise, aphthous-like ulcers, and pharyngitis. Treatment is mostly with topical steroids (see Table 12-1) because of its relapsing-remitting nature. Several medications, especially those used in oncology settings, have been associated with ulcers in the oral cavity. Targeted therapies and biologic agents are used increasingly in the treatment of cancers, autoimmune diseases, and even chronic mucosal disease. Dentists should be familiar with the names of these medications as they may encounter patients taking these medications. These ulcers do not represent aphthous ulcers but are rather considered aphthous-like ulcers because they resolve when the drug is withdrawn and recur only when the patient is rechallenged with the drug. Therefore, a detailed drug history is extremely important when evaluating abrupt-onset oral ulcers. Oral mucositis, ulcerative or otherwise, still represents a major acute complication of cancer chemotherapy. The most stomatotoxic agents include antimetabolites, such as capecitabine, fluorouracil, and methotrexate; alkylating agents, such as cyclophosphamide and melphalan; antimitotics, such as paclitaxel, vinblastine, and vincristine; and anthracycline antibiotics, such as daunorubicin, doxorubicin, carboplatin, cisplatin, and hydroxyurea. Mucosal soreness and sensitivity generally begin about 3 to 5 days after the first infusion, oral erythema or ulcers develop a few days later, and resolution occurs in approximately 15 days. Ulcers that affect the keratinized mucosa of the hard palate, gingiva, or dorsal tongue during chemotherapy are likely caused by herpes infections (discussed later). Topical anesthetics (such as viscous lidocaine or morphine rinses for severe cases) or systemic or narcotic pain medications help relieve symptoms until the ulcers heal. At higher doses, methotrexate acts as a chemotherapeutic agent in the treatment of non-Hodgkin lymphoma, leukemia, and some solid tumors. Oral lesions associated with methotrexate toxicity are typically characterized by dose-dependent erythema and ulceration (broadly termed mucositis). Treatment of these lesions is with topical corticosteroids and, if necessary, dose reduction. Seroepidemiologic evidence reveals that 50% to 60% of adults in the United States have circulating antibodies to the virus, although few would remember experiencing a primary infection. Subsequently, trigger factors such as sunlight, 248 illness, trauma, emotional stress, or menses may reactivate the latent virus in the ganglia, resulting in viral replication and transport via nerves to the skin or mucosal surfaces. Management is directed toward pain control, 250 and definitive therapy is with ganciclovir, valganciclovir, or cidofovir. Oral Ulcers Coxsackievirus (a group of enteroviruses) infection is associated with two diseases most commonly seen in children: hand, foot, and mouth disease and herpangina. Herpangina is characterized by multiple small, coalescent ulcers on the tonsillar pillars and the soft palate. Hand, foot, and mouth disease has a similar oral manifestation with cutaneous vesicles of the hands and feet. Coxsackievirus is also implicated in lymphonodular pharyngitis that causes a sore throat. Treatment includes pain management, hydration, and soft diet until signs and symptoms resolve. Skin lesions are symmetric, erythematous, and edematous papules with a target or bullseye appearance and typically affect the extremities (especially the palms). The history and clinical presentation are usually sufficient for diagnosis, and a biopsy is confirmatory. If M pneumoniae infection is a suspected trigger, the evaluation includes a chest radiograph, polymerase chain reaction testing of throat swabs, and serologic tests. Therapy includes topical and systemic analgesics, skin wound care, and hospital-based supportive care. Mucormycosis appears as black, necrotic, and/or fungating lesions that resemble malignancy; patients with diabetes mellitus (especially if ketoacidotic), neutropenia, or malignancy and individuals who have 251 12 Oral Manifestations of Systemic Diseases Diagnosis is made after biopsy and histopathologic examination, as well as culture and serologic and polymerase chain reaction studies. Treatment requires surgical debridement and aggressive systemic antifungal therapy for all such infections. Necrotic, whitish, ragged epithelial tags from the ruptured blister roof may be seen piled up at the edges of such erosions and ulcers. It is characterized by autoreactive antibodies, usually immunoglobulin G (IgG) and sometimes IgA, that target antigens in the epithelium-attachment complex, resulting in subepithelial blistering and mucosal fragility. One of the major complications is conjunctival scarring that can lead to blindness (hence the older term, cicatricial pemphigoid). Scarring may also involve the larynx and esophagus but fortunately is uncommon in the oral mucosa. This develops when epithelium peels off the gingiva, leaving only exposed connective tissue, which is the basis for a positive Nikolsky sign (slight rubbing leads to dislodgement of the epithelium).

Even more important is that the research erectile dysfunction causes in early 20s discount priligy uk, practice erectile dysfunction pills from china cheap priligy 60 mg free shipping, and educational communities know of these private insurance practices because they constitute real-world erectile dysfunction heart attack buy priligy 90mg on-line, prospective confirmation that the effects of periodontal care to mitigate certain systemic diseases are impotence from vasectomy order priligy with a visa, in fact erectile dysfunction pills side effects cheap 30 mg priligy otc, valid impotence natural treatment generic priligy 60mg without prescription. Some of the dental insurers involved have been acting in the way described earlier for more than a decade. If the effect of periodontal care to reduce total health care costs is not real, their reimbursement practices would have collapsed under their own weight because they would have failed economically a long time ago. In sum, I consider the six insurance studies summarized in the prior section and the prospective actions of the private insurance industry described in this section to be equal to or better than the proof that may have been provided by a well-controlled, large clinical trial. Challenge to the Dental Profession: Moving from Association to Causation I cut my teeth in clinical research, both as an academic researcher and as an industry executive, on the value of the well-controlled clinical trial as the gold standard of evidence required prior to approving a new drug or device, accepting a surgical technique, or changing a therapeutic paradigm. Indeed, the well-executed clinical trial creates a sort of safe space for researchers and thought leaders, and in general it has served society very well to protect against sham products or outright scams through the years. The best examples come from drug development, where side effects often go unnoticed until a given drug is delivered not hundreds or even thousands of times but tens of thousands of times; or perhaps the drug is not given for weeks or months but for years. Further assault on the value of the clinical trial can come in the form of the evidence-based review system, which can devalue scores if not hundreds of studies in a single analysis. Indeed, while the evidence-based approach has done wonders to enhance critical albeit retrospective thinking on clinical design, we are regularly confronted with the need to rethink norms of clinical care because the evidence is weak. I reiterate that the discipline of evidence-based reviews has been a good thing, but I fear that we are abusing the process and are in danger of approaching a situation in which no study is good enough to retrospectively pass muster. Indeed, when was the last time you read an evidence-based review that concluded that the evidence is strong and consistent Continuing along the current path will have the insidious effect of further debasing science in the minds of the public, resulting in a situation in which political opinion, folklore, religion, and such are placed on an equal plane with science (eg, creationism versus evolution). While not directly related to the purpose of this chapter, I urge all who are engaged in evidence-based reviews to set their parameters and choose their words carefully lest the very purpose for which 361 18 the Economic Impact of Periodontal Inflammation the evidence-based process was created is marginalized, with the unintended consequence of demeaning all scientific data on all subjects. Finally, as noted previously, although there never was a well-controlled human trial on the effects of smoking on lung cancer, it is virtually universally accepted that smoking is a contributory cause of lung cancer and that smoking affects 80% to 90% of all lung cancers. When did the data become compelling enough to move the dialogue from association to causation I do not know when the relationship tipped from associative to causal, but it did tip, and it never went back, despite the efforts of the Tobacco Institute and the cigarette industry to malign the causal relationship. I submit that it is past time for the oral health research community to tip the dialogue on the relationship between oral and systemic health from associative to causal. By clinging to a messianic belief that we cannot speak of causation until the large clinical trial is delivered, we are denying society the opportunity to benefit fully from the decrease in hospitalizations and emergency department visits that results from periodontal therapy. In particular, we are denying the large number of individuals who are on public health insurance to benefit in the way those insured by private entities are benefitting. As noted previously, when society loses the indirect systemic benefits of periodontal care, it also loses the direct benefits of oral care, including tooth retention, fresh breath, improved mastication, and the enhanced social acceptance derived therefrom. Arguably no entity has done more to tip the discussion from association to causation than the Santa Fe Group. This group has published a statement on the relationships of oral and systemic health,3,4 which reads as follows: 362 Santa Fe Group Position Statement on Oral-Systemic Interactions After decades of research and thousands of scientific papers, the relationships between oral health, especially periodontal health, and systemic health are well known. Moreover, during the past ten years, data analysis by health economists, and public statements and actions by several large, private dental insurers have identified additional benefits of oral health by revealing that insured individuals who receive treatment for periodontal disease show fewer hospitalizations and reduced cost of care for a number of systemic diseases including diabetes, cardiovascular disease, and stroke. Therefore, the Santa Fe Group has concluded that sufficient evidence now exists that periodontal disease is a contributory cause to certain systemic diseases, and the public should benefit from this knowledge. Specifically, Medicare, Medicaid, and other public and private health insurance programs should incorporate oral health benefits as a component of comprehensive health insurance. These health benefits will not only improve oral health for its own sake, including speech, mastication and social acceptance, but will also produce substantial economic benefits and total health improvement for the public. The Santa Fe Group statement has been used to solidify the importance of oral health to total health, to galvanize support for oral health from numerous not-for-profit organizations in the health care segment, to motivate the global periodontal research community to be more forthcoming, and to endeavor to convince the federal and state governments that it is foolish Reordering Priorities in Medicare and Medicaid Policy to try to save money by cutting dental care benefits. To date, the Santa Fe Group statement has generated great interest and surprisingly little open criticism. While there is much work to do, the dental, medical, and public health communities-hopefully soon joined by critical governmental agencies-are poised to promote the concept that periodontal disease is a contributory cause to many systemic health problems. Will you accept the substantial real-world experience described in the prior section Or will you stay in the safe place of waiting for the large clinical trial that will probably never come What are the risks of stating that the relationship between oral and systemic health is causal as opposed to merely associative Even if the thesis presented herein should be disproved-and I submit that it will not-the outcome of periodontal care will still be positive. People will have better masticatory function, less chance of painful inflammatory flare-ups, fresher breath, less tooth loss, better speech, and enhanced confidence in social settings. Stated another way, there is no significant downside to delivering periodontal care, and the potential benefits, direct and indirect, in terms of total health and in terms of finance are enormous. Reordering Priorities in Medicare and Medicaid Policy One of the many idiosyncrasies of the historic separation of the medical and dental professions is the belief that dental care is not really health care. It is an elective service-a luxury, if you will, or even a cosmetic service that comes in near last in any priority-setting exercise for allocation of research dollars. We see this attitude play out almost every day, as many states choose not to exercise their right to provide dental care under federal Medicaid rules. We see it when states with public dental insurance, even progressive states like California, decide to eliminate dental care first as soon as there is a financial crisis. We even see it in the fact that dental infection is the only bodily infection that Medicare does not routinely cover. Practicing dentists seem to perceive the rules and guidelines that accompany programs like Medicaid and Medicare as an unwieldy intrusion on their independence. This attitude was in play even before the rise of Medicaid services, with its flawed dental reimbursement model, gave dentists good reason to resist the expansion of such programs. Indeed, dentists were opposed to Medicare when it was founded in 1965, well before they began to have difficult experiences with Medicaid reimbursement. The resistance to these federal health programs is actually more principled than practical or self-serving. Nevertheless, any principles that oppose federal involvement in health care delivery must be measured against the societal failure that occurs when low-income indiv iduals are unable to afford health care. To be sure, one-off events such as Missions of Mercy and even Give Kids a Smile are worthy gestures of the charitable nature of many in the dental profession, but they do little to assist a person with an off-cycle, painful dental health problem. The dental profession cannot simply resist efforts to improve health care access; it needs to bring viable plans to the table to sustain the dignity of the profession. A key element of this plan is to parallel reimbursement practices of the private insurance sector in the belief that it makes no sense to proffer a poorly financed plan for dental coverage that no clinical provider is interested in accepting. While it is not the only approach, it is the one on which the most information is published, and it appears to be the broadest approach in that 34 collaborators from more than two dozen agencies and institutions participated in some way. The Jones approach incorporates several important principles, many of which were articulated in the Santa Fe Group symposium on this topic. The primary global benefit in the Jones approach has a specific focus to "prevent pain, inflammation, and infection," which was designed specifically to ensure that all participants in the Medicare oral health benefit have optimal ability to minimize the effects of oral inflammation on systemic health. In contrast, a plan like that proposed in the Avalere report,12 whereby only selected periodontal services are offered only to Medicare recipients who have a diagnosis of diabetes, heart disease, or stroke, is a net saver. The first phase, Level 1, consists of the core global benefit with a primary goal of preventing pain, inflammation, and infection. It therefore includes diagnostic, preventive, nonsurgical periodontal therapy and nonelective oral surgery, reimbursed at 70% of usual, customary, and reasonable fees with no patient copayments to increase participation. Level 2 benefits under the Jones approach would include "restorative, removable, fixed, endodontic and selected implant (ie, two implants under a lower complete denture) as well as a spending cap ($1,500). Thus, even assuming the full benefit of cost reductions from reduced hospitalizations and emergency room visits due to the periodontal care provided, because the global benefit proposed by Jones is available to all seniors, it is a net coster of $4. These net costs can be mitigated (or not) based on additional premiums paid by Medicare recipients as in the current system. At present, Medicare does pay for a very limited amount of dental care, such as eliminating oral infection in Medicare patients who are undergoing organ transplants. This initiative did not estimate the costs or the specific nature of the expanded dental benefits that might be provided, so the economic impact cannot be discussed at this time. The Avalere analysis12 is not actually an initiative but rather a report on which other initiatives are based, in full or in part. For example, the Jones approach acknowledges that the assessment by Avalere would substantially reduce the total cost of the Medicare dental benefits in her proposal. By providing more limited dental benefits (eg, diagnosis and nonsurgical periodontal care) only to a more limited population, the Avalere analysis easily has the best outcome from a purely economic perspective. Using data on the effect of periodontal care on the number of hospitalizations and emergency department visits from the insurance studies described earlier and data on Medicare costs and the numbers of Medicare recipients who have the three signature diseases (diabetes, heart disease, and stroke), Avalere estimated the savings that could be provided if a basic dental benefit consisting of nonsurgical periodontal therapy was added to Medicare. Their summary of the analysis was as follows: We estimate providing a periodontal disease treatment benefit will produce a savings of $63. For example, it assumed only a 5% uptake of the new periodontal benefit in the first year, growing to a 20% utilization of the benefit in year 10. Yet the financial outcome was a net positive beginning in the first year with $500 million in savings and grew to a net benefit of $12. While some might argue that the Avalere analysis would only benefit a small portion of the senior population, the number of people with periodontal disease and one of the three systemic conditions is actually quite large. Therefore, efforts to characterize the Avalere analysis as small in scope are inaccurate. Moreover, the Avalere analysis based the dental benefit on costs of $825 for initial treatment and $250 for biannual maintenance visits. Thus, the program delivers more than two-thirds of a typical, private insurance dental benefit in year 1 ($1,500 per year) and one-third of a private dental benefit in subsequent years. In addition, patients could elect to have other oral health problems treated out-of-pocket once they develop a level of comfort with the dentist who provides the basic periodontal service. At the time of this writing, a number of collaborative efforts are underway to affect "the economic impact of periodontal inflammation" as this chapter is titled. In fact, it is not a stretch to say that some of them were amazed by the data set. Confirmation that the data from 366 the public sector insured parallels that from the private sector insured would provide substantial evidence to prompt the federal government to act on expanded oral care coverage. It is well established that chronic diseases disproportionately impact Medicare beneficiaries and impose a substantial cost on the federal government. It is also well established that untreated oral microbial infections are closely linked to a wide range of costly chronic conditions, including diabetes, heart disease, dementia, and stroke. In addition, oral diseases have been documented by researchers and medical specialty societies as precluding, delaying, and even jeopardizing medical treatments such as organ and stem cell transplantation, heart valve repair or replacement, cancer chemotherapies, placement of orthopedic prostheses, and management of autoimmune diseases. Despite these factors, most Medicare beneficiaries do not currently receive oral/dental care even when medically necessary for the treatment of Medicare-covered diseases. In fact, Medicare coverage extends to the treatment of all microbial infections except for those relating to the teeth and periodontium. There is simply no medical justification for this exclusion, especially in light of the broad agreement among medical specialists that such What Comes Next Moreover, the lack of medically necessary oral/ dental care heightens the risk of costly medical complications, increasing the financial burden on Medicare, beneficiaries, and taxpayers. At least six major insurance carriers offering dental plans provide enhanced periodontal and preventive coverage to targeted enrollees with conditions such as diabetes, heart disease, stroke, head/neck cancers, and transplants. According to some reports, such coverage has realized important benefits, including markedly lower hospitalization and emergency department admission rates as well as substantial cost reductions. On a further note, veterans getting care through the Veterans Health Administration receive medically adjunctive oral/dental treatment in many instances when a dental diagnosis affects their medical prognosis. These are all important steps forward, and medically necessary oral/dental healthcare including periodontal treatment should be provided in traditional Medicare as well. The Medicare program and all its beneficiaries should not be without the vital clinical and fiscal benefits of coverage for medically necessary oral/dental health therapies. Given the significant potential to improve health outcomes and reduce program costs, we urge Congress and the Administration to explore options for extending such evidence-based coverage for all Medicare beneficiaries. Fox Foundation; the Society for Thoracic Surgeons 367 18 the Economic Impact of Periodontal Inflammation this important statement, signed by an almost unprecedented number of organizations from across the health care spectrum, will be used in the coming year in an effort to generate an administrative solution that leverages the power of periodontal care to reduce hospitalizations and emergency room utilization. Coupled with many other efforts by these organizations and other groups, there is reason for some optimism even in a political environment that is toxic, partisan, and struggling for resources. By the time Dr Glick publishes the third edition of this book, I hope we will be able to describe a wonderful success story of improved health complemented by favorable economics. High-risk periodontal pathogens contribute to the pathogenesis of atherosclerosis. Assessing the association between receipt of dental care, diabetes control measures and health care utilization. Contrarily, sinuses grafted with bone substitutes only had rough-surfaced implants, casting doubt on their comparative conclusions. Bone Graft Materials In the first publication on the sinus bone graft technique in 1980, Boyne and James26 used autogenous cancellous marrow from the ilium. Early Swedish studies on the reconstruction of the atrophic maxilla used iliac bone grafts with machine-surfaced implants. In addition, there was a limited choice of bone substitutes and a paucity of research on these alternative materials. Over time, clinicians began to evaluate the use of various alternative bone materials for sinus augmentation. Tricalcium 4 Bone Graft Materials Pjetursson et al31 performed a systematic review that evaluated bone grafting of pneumatized sinuses that had 6 mm or less residual bone height. When they focused on outcomes using only rough-surfaced implants, they found high implant survival rates (> 96%) for all types of grafts.

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Sleep-Disordered Breathing Approximately 4% of adults in the United States have sleep apnea erectile dysfunction at 18 priligy 60mg overnight delivery. Several longitudinal studies have identiied sleep apnea as an independent risk factor for stroke impotence causes and treatment discount priligy 90 mg mastercard. Despite being highly prevalent erectile dysfunction treatment by acupuncture buy priligy with american express, as many as 70% to 80% of patients with sleep apnea are neither diagnosed nor treated zantac causes erectile dysfunction buy discount priligy on line. Patients who are considered to be high risk on the basis of this screening should be referred for polysomnography impotence in 30s cheap 90 mg priligy. Because of its association with stroke risk erectile dysfunction herbal treatment generic priligy 90mg without a prescription, screening for sleep apnea through a detailed history, including structured questionnaires such as the Epworth Sleepiness Scale and Berlin Questionnaire, physical examination, and, if indicated, polysomnography may be considered. Treatment of sleep apnea to reduce the risk of stroke may be reasonable, although its efectiveness for primary pre vention of stroke is unknown. Hypercoagulability he acquired and hereditary hypercoagulable states (thrombophilias) are associated with venous thrombosis, but a relationship with arterial cerebral infarction is based largely on case series or case-control studies. However, this is not the case for case-control studies among older adults with ischemic stroke. A control was matched by age, smoking history, and length of follow-up to each of the 100 patients with ischemic stroke and the 90 patients with deep vein thrombosis or pulmonary embolus. Antiplatelet Agents for Primary Prevention of Stroke Aspirin use is associated with an increased risk of gastrointestinal bleeding. For example, one observational study found that the overall hemorrhagic event incidence was 5. Taken together, these results relect risk but no beneit of aspirin for the prevention of a irst stroke in the general population. Several relevant trials further inform the use of aspirin and other antiplatelet agents for the prevention of a irst stroke. Four additional metaanalyses also found no reduction in stroke with aspirin in subjects with diabetes mellitus. Relatively few women were enrolled in the primary prevention trials that showed a beneit of aspirin in the prevention of coronary heart events but no reduction in stroke. Patients with a reduced ankle-brachial index are at higher risk of vascular events. One trial evaluated the beneit of aspirin in a screened general population cohort with a low ankle-brachial index. Given the small number of participants with stage 4 or 5 chronic kidney disease (estimated glomerular iltration rate <30 mL/min/1. Aspirin might be considered for the prevention of a irst stroke in people with chronic kidney disease. Cilostazol may be reasonable for the prevention of a irst stroke in people with peripheral arterial disease. Aspirin is not useful for preventing a irst stroke in people with diabetes mellitus in the absence of other high-risk conditions. Aspirin is not useful for preventing a irst stroke in people with diabetes mellitus and asymptomatic peripheral artery disease (deined as asymptomatic in the presence of an ankle-brachial index 0. As a result of a lack of relevant clinical trials, antiplatelet regimens other than aspirin and cilostazol are not recommended for the prevention of a irst stroke. Aspirin (81 mg daily or 100 mg every other day) can be useful for the prevention of a irst stroke among women, including those with diabetes mellitus, whose risk is suficiently high for the beneits to outweigh the risks associated with treatment. Conclusion Physicians and scientists should take pride in the advances that continue to be made in preventing stroke. With so many interventions, optimization of stroke prevention for individuals requires systems of care that identify risk factors as they emerge and that gain control of emerging risk factors safely, expeditiously, and cost efectively. Access to care is necessary but not suicient to guarantee optimal stroke prevention. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Dementia afects approximately over 5 million people in the United States to varying degrees. Only approximately 1 in 100 individuals age <65 years are thought to be afected by dementia, but this proportion reaches as many as one-half of individuals age >85 years. A number of common causes of cognitive impairment are reviewed in this chapter (Box 94. Strokes do not cause Alzheimer pathology, but they may contribute to cognitive dysfunction in patients who already have Alzheimer pathology. Small vessel ischemic strokes, common in aging, are seen most commonly in the white matter, basal ganglia, and thalamus and do not necessarily mean that the patient has vascular dementia. Other important pathologic features include reduced brain weight by approximately 200 to 300 g, atrophy of hippocampus and of temporal, parietal, and frontal cortex, and cerebral amyloid angiopathy (often found in blood vessels) leading to small hemorrhages. Patients cannot remember new information, become disoriented, and show poor judgment and problem-solving skills. Apathy develops early, whereas other behavioral problems such as irritability, exacerbation of premorbid personality traits, and aggression often develop later. Patients continue to lose function until they require around-the-clock care, usually in a long-term care facility. Additional tests that may be important for diagnosis in speciic circumstances are in Box 94. Structural imaging is also important to rule out other etiologies such as large strokes, tumors, hemorrhages, and hydrocephalus. It is not necessary, however, in the evaluation of the routine patient whose diagnosis is straightforward. Progressive supranuclear palsy and corticobasal degeneration should also be considered if there is parkinsonism. Chronic traumatic encephalopathy should be considered if there is a history of repetitive head trauma, usually associated with military combat, football, boxing, or other contact sports. Clinical Presentation he chief clinical manifestation is memory and/or other cognitive loss reported by the patient or informant or noted by the clinician. By neuropsychologic testing, the memory and/or other cognitive impairment is greater than what one would expect adjusted for age and education. Activities of daily living are also largely preserved, and, as a result, the patient is not considered demented. We would only recommend ordering such a scan, however, for one of the reasons discussed earlier. Early cognitive and afective symptoms may include irritability, irascibility, apathy, introversion, and depression. In the severe stages, the patient is typically conined to a wheelchair, and more severe chewing and swallowing diiculties, drooling, coughing, spluttering, and choking are common. Symptomatic treatments that are worth trying include levodopa/ carbidopa (Sinemet) and memantine or amantadine. Over time the afected limbs become more rigid, where rapid movements such as pronation/supination and alternating inger tapping become impaired. Successfully treating hallucinations is diicult, and pharmacologic treatment should be initiated when hallucinations become threatening or otherwise problematic. Only atypical neuroleptics should be used, such as quetiapine (Seroquel) at bedtime, because traditional neuroleptics such as haloperidol (Haldol) are highly likely to cause worsening parkinsonism. Overview Patients classiied as having mixed dementia of cerebrovascular disease plus a neurodegenerative disease probably make up 10% to 15% of all dementias. Cognitive impairment and dementia can occur in a variety of ways, with etiologies including large cortical strokes, small vessel ischemic disease, lacunar infarcts, and other etiologies. Small vessel ischemic disease (subcortical ischemic vascular disease) is attributable to two processes, lipohyalinosis and microemboli. Multiinfarct dementia (cortical vascular dementia or poststroke dementia) is typically as a result of multiple cortical strokes and most commonly caused by large emboli because of a proximal source such as cardioemboli arising from atrial ibrillation. Clinical Features he typical symptoms of the diferent types of VaD are shown in Table 94. Progressive nonluent aphasia is characterized by efortful speech, phonologic and grammatical errors, reading and writing diiculty, and progressive loss of speech. She has a past medical history of longstanding hypertension, diabetes mellitus, and peripheral vascular disease. Whereas in the past he was very calm and pleasant, he has become "nasty"-cursing in public and making unwanted advances toward women. His work performance is also sufering, and he has been given a warning by his employer that he needs to begin meeting deadlines. A 75-year-old man presents for evaluation of memory loss that started 3 years ago and has worsened progressively. He often misplaces his belongings, and his wife says he repeats questions often and is no longer able to manage his bills or do their taxes. Although the prevalence of epilepsy is estimated to be around 3%, approximately 11% of the population gives a history of having had a seizure at some time in their life. Among patients visiting an outpatient neurology facility, seizure disorder or epilepsy constitutes one of the ive most common conditions. In terms of physical and emotional disability, as well as the expense involved in evaluation and drug treatment, seizures constitute a major public health problem. Despite their prevalence and importance, seizure disorders are poorly understood by the general public and some general physicians are not comfortable in managing them. In addition, epilepsy is not one entity, but it represents diverse conditions with varied causes and mechanisms. A seizure is a transient alteration in neurologic function resulting from a sudden, abnormal, excessive discharge in the cerebral cortex or underlying hemispheric structure. S occurring in children age 0 to 6 years in the context of a rapidly rising body temperature; temporal lobe epilepsy (a common term for seizures with atypical cognitive or physical symptoms) includes either focal aware/simple partial seizures or focal with impaired awareness/complex partial seizures. Clinical Diagnoses Accurate characterization of the seizure type is crucial to efective management, both for diagnostic evaluation and for choice of drug therapy. In seizures with impaired awareness, reports from both the patient and bystanders may contribute to accurate classiication. It is crucial to recognize that there is often a progression from one seizure type to another. Generalized seizures primarily denote metabolic or genetic etiologies; focal seizures primarily denote structural anomalies or damage to the cortex, although genetic factors may also be at play. Most generalized epilepsies have their onset during childhood/adolescence, whereas focal epilepsies tend to be more prevalent in adults. Classification Since 1970 seizures have been classiied by most neurologists according to the International Classiication described initially by Gastaut. According to this scheme, febrile convulsions are generalized motor tonic-clonic seizures (grand mal) 1012 Differential Diagnosis Absence seizures, previously called petit mal seizures, are a disorder of children, beginning after the age of 2 years and before puberty, often with tens or hundreds of episodes per day. Motor (automatisms, atonic, clonic, epileptic spasm, hyperkinetic, myoclonic, tonic) 2. Unknown onset or automatisms in the form of lip smacking, chewing, or fumbling movements of the ingers. Such patients rarely fall during an episode and may continue their activity immediately after the spell because they do not experience postictal confusion. Childhood/juvenile absence epilepsy is not a common disease, accounting for only 12% of epilepsy diagnoses in one of the largest prospective community-based studies. If prolonged, focal nonmotor seizures with impaired awareness may present as nothing more dramatic to the patient than a period of several minutes for which the patient has no recollection. To observers, the behavior during that period may have been characterized by continuation of well-practiced skills, such as driving or riding a bicycle, accompanied by a vacant stare and lack of contact with the surroundings. Unlike absence seizures, such episodes are not invariably related to 3-per-second spike-and-wave activity, and they occur much less frequently. Absence seizures invariably begin before age 15 years and cease by age 20 years in 80% to 90% of alicted individuals. If persisting beyond age 25 or 30 years, they may suggest a diagnosis of focal seizures with impaired awareness. Approximately 50% of children with absence/petit mal seizures develop generalized/grand mal seizures that may persist into adult life. Absence seizures may be complicated by the occurrence of other types of seizure, including episodes of myoclonic jerking and drop attacks. If the absence seizures in such patients display typical 3-per-second synchronous spikeand-wave activity, the prognosis is good. Generalized motor seizures or focal to bilateral tonicclonic seizures, previously called primary or secondary generalized/"grand mal" seizures, are easily diagnosable to the bystander, although the patient may be unaware of anything other than a "black out" and the sore muscles, headache, confusion, and fatigue that often follow. No aura is experienced in about half of generalized seizures, presumably because of the rapid spread of seizure activity. After 2 or 3 minutes, the clonic phase ends with a deep inspiration, the musculature relaxes, and color returns to the face and extremities. After another few minutes, consciousness returns, although the person is often confused and may be agitated. Complete recovery follows a period of several hours of sleep, although some patients may exhibit focal neurologic deicits, such as hemiparesis, hemisensory loss, or aphasia that gradually resolve over 48 to 72 hours. Some patients with a "new" stroke may in fact have a postictal paralysis following a seizure from the scar left by a previous stroke. Generalized seizures often occur in small lurries of several seizures over a few hours; this is a common pattern in alcohol withdrawal seizures during the irst 6 to 36 hours after the sudden cessation or reduction in the consumption of alcohol. A small percentage of epileptic patients will at some time have a series of seizures between which consciousness is not recovered, status epilepticus. However, transient ischemic attacks rarely lead to loss of consciousness, whereas prolonged confusion or postictal sleepiness does not follow syncope. Moreover, the patient with vasodepressor syncope has a more prolonged premonitory phase consisting of nonneurologic symptoms including weakness, nausea, lightheadedness, and diaphoresis, as opposed to the sudden loss of consciousness that can occur in seizures. Although a brief tonic phase, sometimes followed by a few clonic jerks, can occur in syncope of any cause when it is accompanied by cerebral hypoxia; fecal incontinence, cyanosis, stertorous breathing, and a prolonged course (>1 minute) usually implies a true seizure occurrence.