Rebecca Ann Burbridge, MD

• Associate Professor of Medicine
• Director of Advanced Endoscopy
• Associate Director of Clinical Endoscopy

https://medicine.duke.edu/faculty/rebecca-ann-burbridge-md

Diabetic patients therefore should be counseled to use efective contraception until HbA1c is controlled arthritis fasting diet generic diclofenac 100mg overnight delivery. Although expert opinion varies about the speciic target glucose levels arthritis rheumatoid treatment natural buy generic diclofenac from india, glucose goals during pregnancy are Chapter Review Questions 1 arthritis pain mayo clinic purchase diclofenac discount. Continue glyburide arthritis pain on right side order diclofenac with american express, and start sliding scale regular insulin before meals and bedtime arthritis pain control uk buy diclofenac on line amex. Management of hyperglycemia in type 2 diabetes arthritis in dogs prognosis order discount diclofenac on line, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by International Diabetes Organizations. Even with excellent glucose control, patients with type 1 diabetes (T1D) were recently reported to have double the risk of death and triple the risk of cardiovascular death compared with nondiabetic peers. On average, individuals with type 2 diabetes (T2D) have a lower life expectancy by 6 years, and up to 80% of deaths are from cardiovascular causes. Complications associated with diabetes such as kidney, eye, and nerve damage may signiicantly decrease quality of life. Recent studies have shown improvement in mortality trends and complication rates in patients with diabetes, likely demonstrating the beneits of current therapeutic paradigms. Control Real-Time Glucose Measurements Measuring glucose control is of paramount importance in managing diabetes. However, most devices are more accurate than this, with the average diference from reference range being 5% and with 99% of values being within 20% of reference when using good technique. For patients on insulin, selfmonitoring at various times of the day will assist in recognizing patterns of hypoglycemia and hyperglycemia, and many insulin regi mens require the patient to calculate dosing based on glucose values. For patients not on insulin and not at risk for hypo glycemia, the role of selfmonitoring is less critical but may help the patient to recognize the impact of daily activities such as diet and exercise on glucose levels. Devices are now available that measure glucose "continuously" (approxi mately every 5 minutes) with a small catheter inserted sub cutaneously and changed every 1 to 2 weeks. Measuring Long-Term Glucose Control he HbA1c level has been the primary measurement to inform providers and patients as to the level of chronic glycemia. HbA1c is a product of an irreversible nonenzymatic glycosylation of the hemoglobin molecule. Despite some concerns about interpretability in individual patients, HbA1c levels have had excellent predictive correlation in many studies of diabetic complications. Because of its dependence on hemoglobin, any condition that impacts red cell life span (splenectomy, hemolysis, blood loss) will impact the HbA1c level. Also, hemoglobinopathies may have variable efects on HbA1c measurement depending on the method used to measure HbA1c. In a situa tion in which the HbA1c may not relect longterm glycemia, other glycosylated proteins may be measured. Of importance, although the HbA1c is a convenient method of determining overall glycemic status, it does not identify patterns of glycemic variability and can mislead providers in the evaluation of hypoglycemia risk. Nearly 75% of subjects experienced a glucose level <60 mg/dL despite the elevated HbA1c, and importantly, of the 102 hypoglycemic episodes recorded, 93% were unrecognized by inger-stick glucose measurements performed four times a day or by symptoms. Complications of Diabetes: General Overview Acute Complications Hypoglycemia Hypoglycemia is the primary limiting factor in normalizing glucose levels in diabetes. Patients usually will begin to have adrenergic symptoms such as diaphoresis, tremor, and palpitations as glucose levels drop <70 mg/dL and will develop neuroglycopenic symptoms such as altered mental status and seizure with glucose levels <40 mg/dL. Patients treated with medications that may cause hypoglycemia should be taught to prevent hypoglycemia in predictable situations. Patients need to learn how to treat hypoglycemia with oral ingestion of simple sugars. For those at particular risk, family members or caregivers should receive instruction on how to administer glucagon. All conditions are driven by a relatively low insulin level that cannot meet the metabolic demand and/or overcome acute insulin resistance, which leads to persistent hyperglycemia and glycemic osmotic diuresis. In any patient presenting with a hyperglycemic crisis, a precipitating cause (nonadherence to medication, new medications, infection, cardiovascular event) should be sought. Chronic Complications Overview Chronic complications have generally been divided into two categories: microvascular and macrovascular. Microvascular complications resulting from diabetes include retinopathy, nephropathy, and neuropathy. Macrovascular complications include coronary artery disease, cerebrovascular disease, and peripheral vascular disease. However, damage associated with diabetes may extend to other more recently recognized areas such as skin, musculoskeletal tissues and myocardium, and the liver. Finally, recognition and management options for select complications will be discussed individually. In the past, mortality caused by hyperglycemic crisis has been reported to be the highest at extremes of age, but more recent studies suggest that mortality rates for Glucose Hypothesis Elevated levels of glucose have been correlated with multiple cellular abnormalities that may contribute to complications associated with diabetes. For many tissues in the body, glucose transport across the cell membrane is not regulated by insulin, and in hyperglycemia the cell is confronted with high intracellular glucose and glucose metabolites. Glucose variability itself has also been hypothesized to contribute to end-organ damage leading to long-term complications. Major Trials Examining the Glucose Hypothesis Two major trials published in the 1990s examined the impact of glucose control on long-term complications in diabetes in patients who were early in the course of their disease and without signiicant preexisting complications. For retinopathy, the risk reduction was 50% to 75%, nephropathy 40% to 50%, and neuropathy 60%. However, despite similar control now for many years, the intensively treated group continues to have lower risk for microvascular complications, a phenomenon termed metabolic memory. Analysis of cardiovascular events 18 years after the start of the trial showed that risk was reduced signiicantly by 42% in the intensively treated cohort, and even at 30 years, cardiovascular risk still was reduced by 30%. In intensively treated patients, the goal was to maintain fasting glucose <108 mg/dL; in the control groups, medications were added for glucose levels >270 mg/dL (clearly not current standard practice). As expected, a high number of subjects in the conventional group required glucose-lowering medications, but HbA1c diferences were maintained between the groups: 7% for intensive group and 7. However, when looked at by HbA1c reduction, it is estimated that for every 1% decrease in HbA1c, risk of microvascular disease decreased by 37%. Ten years after the trial ended, HbA1c levels in the two groups also converged at 7. Evaluation of cardiovascular events showed a 16% reduction in the intensively treated group, which did not quite reach statistical signiicance during the trial but did reach signiicance after 10 years. In the metformin treatment arm, although the HbA1c reduction diferential between the two groups was only 6% (7. Microvascular risk reduction was 37%, and cardiovascular risk improved by 40% to 50% in the tightly treated group. One of the earlier studies in large numbers of patients with diabetes was the Heart Protection Study. Within just 5 years, signiicant reduction in any cardiovascular event in the treatment group was noted. Later studies have shown improvements in primary prevention with 10 mg atorvastatin versus placebo in type 2 patients and for secondary prevention with 80 mg atorvastatin versus 10 mg atorvastatin. Cardiovascular outcomes were not improved after 10 years, but microvascular risk reduction, particularly in nephropathy progression, was demonstrated. Complications of Diabetes: Specific Conditions Retinopathy Diabetes is the leading cause of blindness in the United States and other developed countries. Diabetes also increases risk for other ocular complications such as cataracts and glaucoma. Screening is currently recommended after 5 years of T1D but at onset of T2D (because of potential delay in diagnosis). Screening should be annual, but, if after several years no retinopathy is noted, frequency can be decreased to every 2 years. In a Medicare study comparing 119 pairs of patients who did receive guideline care versus the closest matched control who did not, low vision/blindness was substantially reduced over a 3-year period among persons who received recommended levels of care. It is thought that the decline in prevalence and incidence of retinopathy and vision impairment is the result of improved management of hyperglycemia, hypertension, and dyslipidemia. Paradoxically, short-term intensive control has been reported to potentially worsen retinopathy. Reninangiotensin system inhibition has been shown to be efective for primary prevention in type 1 patients. Advances in knowledge of the pathophysiology of retinopathy have led to some novel treatment approaches. Severe preprolifera tive retinopathy and proliferative retinopathy are usually treated with panretinal photocoagulation. Glomerular changes are progressive and start with podocyte loss, glomerular basement membrane thickening, mesangial expansion, and inally nodular sclerosis. Low levels of albuminuria spontaneously regress in up to 40% of patients with T1D, and this can occur in T2D as well as in response to metabolic control. A referral to nephrology is reasonable at this point to discuss interventions that slow progression and when appropriate to introduce kidney or combined kidney/pancreas transplant options. Because smoking increases risk and rate of disease progression, smoking cessation is important to address. Twenty-ive percent of patients may report symptoms, up to 50% may have physical indings present, and 90% may have abnormalities detectable with advanced testing. Duration of diabetes and level of glucose control are primary correlates for neuropathy through mechanisms previously mentioned. Proximal and distal nerves, large and small nerve ibers, and single and multiple nerves may all be involved. Patients may have symptoms or signs involving cardiac, gastrointestinal, and genitourinary systems. Because of the lack of a speciic test abnormality deining neuropathy, other causes of symptoms should be excluded. Early physical indings of neuropathy include loss of distal deep tendon relexes, loss of normal sinus rhythm, and diminished detection of vibration with a 128 Hz tuning fork. Loss of detection of a 10-g monoilament pressed on the foot until the monoilament bends correlates with high risk for ulceration and should prompt referral to podiatry. Cotton to test light touch and a cold tuning fork to detect temperature sensation are easily available additional tests. Advanced testing with nerve conduction velocity should only be needed when the clinical picture is not clear. Diabetic foot disease is multifactorial and is caused by both neuropathy and peripheral vascular disease. Dry skin arising from sudomotor dysfunction leads to thickened and cracked skin that predisposes to infection. Ulceration, bony deformity, osteomyelitis, and amputation are the consequence of diabetic foot disease. Long-term studies of glucose control in type 2 patients have not been as conclusive. No disease-modifying drugs have been released for management of neuropathy so treatment is entirely oriented to symptom relief. Drugs that have been found to be beneicial for symptom relief include the anticonvulsants pregabalin, gabapentin, and topiramate; antidepressants duloxetine, venlafaxine, amitriptyline, and nortriptyline; opioids tapentadol and tramadol; and topical capsaicin. Opioids such as sustained-release morphine should be reserved for patients in whom other options have failed. Patients with diabetes have two to four times the risk of patients without diabetes for cardiovascular death and stroke. However, as noted in studies mentioned previously, in long-term studies, glucose control early in disease course will also lower risk. Trials have looked at routine use of more advanced screening such as stress testing and have not found any beneit. Choice of glucose-lowering therapy can have an impact on cardiovascular outcomes, but this area of medicine is not without controversy. Many population-based studies have found improved cardiovascular outcomes in patients on metformin, but selection bias may play a role in the indings. A recent randomized study showed improved cardiovascular outcomes with metformin compared with glipizide. Sulfonylurea agents have long raised concern for worsening cardiovascular outcomes. Statins, however, can increase risk of diabetes in patients with prediabetes by 9%, although the mortality and morbid ity beneit of statins in patients with established diabetes far outweighs any potential metabolic risk. Niacin is no longer recommended for use in patients with diabetes, but ezetimibe in combination with moderate-dose statin therapy may ofer modest beneit over statin therapy alone. Musculoskeletal Complications of Diabetes Musculoskeletal complications in diabetes are underrecognized. Diabetic cheiropathy is characterized by thickened skin and limited mobility in ingers and hands (prayer sign) and leads to lexion contractures, such as Dupuytren contracture and lexor tenosynovitis. Adhesive capsulitis of the shoulder and carpal tunnel are other common manifestations of musculoskeletal involvement. Relex sympathetic dystrophy, muscle infarction, and difuse idiopathic skeletal hyperostosis are increased in diabetes. A 44-year-old man with T2D diagnosed 4 years ago returns for follow-up of recent laboratory tests showing an HbA1c of 8. A 60-year-old woman returns for routine diabetes follow-up and is concerned about gradual onset of blurred vision occurring over months. She has had diabetes for 20 years, treated initially with oral agents, but she is now taking a multidose regimen of insulin analogues. She has background retinopathy noted on regular funduscopic examinations, although her last examination was 2 years ago. Visual ields are intact to confrontation, tests of extraocular muscles are normal, and your nondilated funduscopic examination shows microaneurysms and cotton wool spots.

Diseases

• Retinitis pigmentosa-deafness
• Precocious puberty, gonadotropin-dependent
• Ectodermal dysplasia Bartalos type
• Alopecia mental retardation syndrome
• Macrothrombocytopenia with leukocyte inclusions
• Neurofibromatosis type 2
• Occupational asthma - animals, insects and fungi
• Myoglobinuria dominant form
• Purtilo syndrome

Other vitamin D sterols arthritis in fingers osteoarthritis purchase diclofenac 50mg on line, such as the vitamin D prohormones dog arthritis pain relieve purchase generic diclofenac line, are also available and work similarly to calcitriol but seem to cause less hypercalcemia arthritis medication and pregnancy buy cheap diclofenac on line. Some observational evidence supports a survival beneit with the use of paracalcitol over calcitriol arthritis in the back exercises generic diclofenac 100 mg on line, but the explanation for this beneit remains elusive arthritis nos icd 9 buy line diclofenac. Cinacalcet is now also widely used in managing patients in combination with active vitamin D and one or more phosphate binders arthritis pain in ankles order generic diclofenac online. Serum levels of calcium and phosphorus need to be monitored every 3 months after starting therapy with high-dose ergocalciferol. Persistently increased serum phosphorus levels should prompt discontinuation of vitamin D therapy. Medical history is notable for hypertension diagnosed by his primary care physician about 15 years ago. Medications include hydrochlorothiazide 50 mg/d and atorvastatin 10 mg once daily. Evidence indicates that elderly African-American patients do not beneit from angiotensin blockade. Management of his hypertension should include workup for the possibility of sleep apnea syndrome. A 44-year-old man is seen in follow-up for management for his presumed ibuprofen-associated gastritis. Two weeks previously, he was told to discontinue his ibuprofen, and the cimetidine was begun. You are asked to consult on a 62-year-old AfricanAmerican male diabetic with nephropathy. All of the following would be changes seen on the electrocardiogram compatible with hyperkalemia, except: A. A 52-year-old African-American female presents to the emergency department with unstable angina. Her cardiologist asks you for an estimate of her risk of developing contrast nephrotoxicity. Testing for chronic kidney disease: a position statement from the National Kidney Foundation. In the United States, the National Health and Nutrition Educa tional Survey reports an incidence of approximately 30% in individuals 18 years and older. Essen tial hypertension is the most prevalent hypertension type, afecting 90% to 95% of hypertensive patients. Fiftythree percent of patients with hypertension are being treated with medications. Hypertension is a major risk factor for cardiovascular dis ease, heart failure, stroke, left ventricular hypertrophy, and chronic kidney disease. Workup of hypertension should include a thorough history and physical examination and laboratory workup (Box 65. Common and uncommon causes of secondary hypertension and clues to secondary causes of hypertension are shown in Box 65. Remarkably, there was also a signiicant 25% reduction in allcause mortality in the intensivetreatment group. Yes Algorithm for the Eighth Joint National Committee recommended first-line treatment of hypertension. Risk factors for malignant hypertension include cigarette smoking, black race, medication nonadherence, and individuals with secondary hypertension. Before efec tive therapy, life expectancy was <2 years, with most deaths resulting from stroke, renal failure, or heart failure. With current therapy, including dialysis, the survival rate at 1 year is >90% and at 5 years is >80%. Renal biopsy (if one is performed) usually demon strates arteriosclerosis and ibrinoid necrosis. Neurologic presentations include occipital headaches, cerebral infarct, cerebral hemorrhage, or hypertensive encephalopathy. Hypertensive encephalopathy is a symptom complex com prising severe hypertension, headache, vomiting, visual dis turbance, mental status changes, seizure, and retinopathy with papilledema. Focal signs and symptoms are uncom mon and may indicate another process, such as cerebral infarct or hemorrhage. Patients with malignant hypertension are usually admitted to an intensive care unit for continuous cardiac monitoring and frequent assessment of neurologic status and urine output. A rapid assessment for target organ damage is performed, both clinically and by a laboratory workup. Use of shortacting antihy pertensive agents administered intravenously is recom mended (Table 65. Resistant hypertension is present in 5% of patients with hypertension in a general practice setting, but it is much more common in specialty settings such as a renal clinic. Because a suboptimal dosing regimen or inappropriate antihypertensive drug combination is the most common cause of resistant hypertension, the irst step in management is to review the medication regimen. One of the most important interventions is to target subtle or clinically apparent extracellular volume expansion by either adding a diuretic agent or increasing the dose of diuretic, or by changing the diuretic class based on kidney function. Options for a fourth agent include a vasodilator, beta-blocker, or peripheral alpha-blocker. Renal denervation became an attractive option for resistant hypertension after the publication of the Symplicity 1 and 2 studies. Endocrine Hypertension Syndromes Endocrine hypertension includes the following disorders. Primary Aldosteronism Primary hyperaldosteronism is the most common form of endocrine hypertension. Excessive aldosterone production by the adrenal glands leads to luid retention, potassium loss that manifests as mild-to-moderate hypokalemia, metabolic alkalosis, and hypertension. If the plasma aldosterone concentration is >20 ng/dL and the ratio is >30, the sensitivity and speciicity for primary aldosteronism are >90%. Adrenal venous sampling probably has its greatest utility in the setting of either totally normal adrenal imaging despite biochemical evidence for primary aldosteronism or settings in which bilateral adrenal pathology is present on imaging. Bilateral adrenal hyperplasia is best treated with medications such as spironolactone or eplerenone. Surgery is the treatment of choice for the lateralizable variants of primary hyperaldosteronism. A more detailed discussion is provided in the endocrinology section of this book (see Section 5). These tumors produce excessive amounts of epinephrine, norepinephrine, or other catecholamines. The classic triad of symptoms in patients with a pheochromocytoma consists of episodic headache, sweating, and tachycardia. About 10% of these tumors are located outside the adrenal glands (extraadrenal) in various locations in the body. However, pseudohypertension and "white-coat hypertension" are common, and readings outside the oice should be emphasized. Starting doses for drug therapy should be lower than those used in younger adults. Presence of a hybrid or chimeric gene on chromosome 8q consisting of the regulatory region of the 11-betahydroxylase gene coupled to the coding sequence of the aldosterone synthase gene. Clinical: Rare familial renal tubular defect characterized by hypertension and hyperkalemic metabolic acidosis in the presence of low renin and aldosterone levels. Clinical: Early-onset severe hypertension, hypokalemia, metabolic alkalosis in the setting of low plasma renin and aldosterone, low rates of urinary aldosterone excretion, and a family history of hypertension. Pathophysiology: Pseudoaldosteronism due to ingestion of certain types of licorice (usually black licorice). Hypertensive patients age >80 years should have their treatment continued if the antihypertensive regimen is well tolerated. Eclampsia is defined as seizures that cannot be attributable to other causes in a woman with preeclampsia. New-onset proteinuria (300 mg/24 h) in a woman with hypertension but no proteinuria <20 weeks of gestation. Preeclampsia/ eclampsia Hypertension in Diabetics he prevalence of hypertension is greater among patients with diabetes mellitus than nondiabetics. However, there was a lower risk of total and nonfatal strokes in the intensive therapy arm but a higher risk of serious adverse events. About 20% to 25% of women with chronic hypertension develop preeclampsia during pregnancy. Women with preexisting endorgan damage from chronic hypertension should have a lower threshold for starting antihypertensive medication. Hypertension in Pregnancy Hypertension is the most common medical problem encoun tered during pregnancy, complicating 2% to 3% of preg nancies. Hypertension during pregnancy is an important cause of both maternal and fetal morbidity and of maternal mortality, especially in the developing world. Hypertensive disorders during pregnancy are classiied into four categories by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy: (1) chronic hypertension; (2) preeclampsia/eclampsia; (3) pre eclampsia superimposed on chronic hypertension; and (4) gestational hypertension (Table 65. Preeclampsia he incidence of preeclampsia in the United States is esti mated to range from 2% to 6% in healthy nulliparous women. Other factors, includ ing hypoxia and perturbations in the reninangiotensin aldosterone system, among other factors, also seem to be important (Wang et al. Magnesium sulfate is the drug of choice for seizure prophylaxis in women with preeclampsia. Treatment is started by administering an intravenous loading dose of 4 to 6 g magnesium sulfate, followed by a maintenance dose of 1 to 2 g per hour. Management of Mild Preeclampsia Delivery is the only cure for a pregnancy complicated by mild preeclampsia; if the mother is >37 weeks, the fetus should be delivered. Vaginal delivery is the irst choice but with induction of labor regardless of cervical status; cesarean section should be performed based on standard obstetric cri teria. From National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy Hypertension. Vaginal delivery is the irst choice, and cesarean section should be based on routine obstetric indications. Women with severe preeclampsia who have nonreassuring fetal status, ruptured membranes, labor, or maternal distress should be delivered regardless of gesta tional age. Patients should be instructed to report any headache, visual changes, epigastric pain, or decreased fetal movement. Risk factors for preeclampsia include nulliparity, age >40 years, a family history of preeclampsia, multiple gestations, chronic hypertension, antiphospholipid antibody syndrome, underlying renal disease, obesity, diabetes, and thrombophilia. Clues to diferentiate preeclampsia from chronic hypertension include the presence of visual distur bances such as scintillations and scotomata; the presence of newonset headache described as frontal, throbbing, or similar to a migraine headache; newonset epigastric pain; and rapidly increasing or nondependent edema (edema is no longer included among the criteria for diagnosis of preeclampsia). Glomerular endothelial injury in the kidneys is the mech anistic explanation for proteinuria, extracellular volume expansion, and hypertension. Importantly, hydralazine may result in maternal hypotension, which may subsequently result in a nonreassuring fetal heart rate tracing in the fetus. Labetalol is a selective alpha-blocker and nonselective beta-blocker that produces vasodilatation and results in a decrease in systemic vascular resistance. Labetalol decreases supraventricular rhythm and slows the heart rate, reducing myocardial oxygen consumption. Used in a severe hypertensive emergency, nitroprusside results in the release of nitric oxide, which subsequently results in significant vasodilation. Therefore its use should be reserved for postpartum care or just before the delivery of the fetus. Eclampsia and preeclampsia account for >60,000 maternal deaths each year worldwide. Of women who initially present with apparent gestational hypertension, about one third develop the syndrome of preeclampsia. Gestational hypertension may, however, be a harbin ger of chronic hypertension later in life, and followup with a primary care physician is reasonable. Management of Eclampsia he most important goals are to stabilize the patient, deliver the fetus after the patient has been stabilized, and prevent further seizure activity. Stabilization of the patient involves protection of the airway, oxygen therapy, and establishing intravenous access. However, if vaginal delivery is associated with delay and/or fetal or maternal distress, then immediate cesarean section is preferred. Intrapartum compli cations include fetal growth retardation, nonreassuring fetal heart rate patterns, and placental abruption. On the other hand, invasive techniques with more accurate diagnostic potential can produce a worsening of renal function because of contrast toxicity and complications related to the procedure itself. When the history is highly suggestive and there is minimal risk for radiocontrast-mediated renal injury, conventional angiography or digital subtraction angiography is the appropriate initial test. In patients at risk of contrast nephropathy, a carbon dioxide angiogram should be considered. At a median followup of 43 months, the rate of the primary composite endpoint (death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insuiciency, or need for renal replacement therapy) was no diferent between the two arms. However, whether the study indings are generalizable for all patients with renal artery stenosis.

He has increased the frequency of his short-acting bronchodilator use without improvement in his symptoms arthritis cream feet purchase cheapest diclofenac and diclofenac. Vital signs reveal a heart rate of 126 beats per minute arthritis relief while on coumadin buy generic diclofenac on line, blood pressure 110/62 mm Hg arthritis in neck pinched nerve diclofenac 75mg online, respiratory rate 22 breaths per minute arthritis l5 s1 discount diclofenac 75mg line, O2 saturation 85% on room air extreme arthritis in dogs order discount diclofenac online. A 47-year-old woman with known peptic ulcer disease presents with a 3-day history of epigastric pain arthritis pain medication side effects generic diclofenac 75mg on-line, profuse vomiting, and inability to tolerate oral food or luids. Blood pressure is 88/42 mm Hg, pulse rate 97 beats per minute, and mucous membranes are dry. Blood pressure is 92/65 mm Hg, pulse rate 62 beats per minute, weight 132 lb, height 5 ft 9 in. She has decreased right basilar breath sounds and right-midlung crackles and rhonchi. His SpO2 is 89% on ambient air, and his respiratory rate is 11 breaths per minute. A 65-year-old man with a history of insulin-dependent diabetes, hypertension, and end-stage renal disease on hemodialysis is admitted to the hospital for treatment of lower extremity cellulitis. On presentation she is afebrile, her heart rate is 120 beats per minute, blood pressure is 105/45 mm Hg, respiratory rate is 23 breaths per minute and unlabored. Femoral vein cannulation carries a higher risk of arte rial puncture than internal jugular or subclavian site. Subclavian vein catheterization is associated with a higher infection rate than internal jugular vein catheterization. Routine exchanges of catheters every 7 days is asso ciated with a decreased rate of catheter infection. Which of the following interventions is not universally recom mended to reduce incidence of ventilatorassociated pneumonia On presentation, she has a respiratory rate of 28 breaths per minute with deep respirations. Cardio vascular examination shows a regular rate and rhythm with a normal S1 and S2. A decision is made to intubate an asthmatic patient for impending respiratory failure. During intubation, the patient receives sedation and a short-acting paralytic agent. Laboratory studies on presentation reveal serum sodium 140 mEq/L, white blood count 19,000/L (89% polys, 4% bands), potassium 4. A 60-year-old man is admitted with severe midepigastric abdominal pain radiating to the back. Decisions regarding end-of-life care are guided by which of the ethical principles outlined below He is currently afebrile, his heart rate is 96 beats per minute, his blood pressure is 104/62 mm Hg, and his respiratory rate is 32 breaths per minute with use of accessory muscles. A 67-year-old woman with a history of hypertension and coronary artery disease presents with 72 hours of progressive lethargy, fever, and dysuria. Her heart rate is 126 beats per minute and regular, blood pressure is 70/46 mm Hg, and respiratory rate is 24 breaths per minute unlabored. He is afebrile, his heart rate is 126 beats per minute, and his blood pressure is 92/58 mm Hg. Which of the following represented a signiicant risk of administration of activated protein C He has now developed bilateral pulmonary iniltrates requiring mechanical ventilation. A 19-year-old female intubated, unresponsive status post lorazepam overdose 2 hours earlier C. In summary, a variety of injuries can occur as a result of smoke inhalation, including direct thermal injury and toxic inhalations. A variety of complications can arise from central line placement, including bleeding (hematoma, arterial puncture), pneumothorax, air embolization (0. Risks of central line insertion vary by site, and it was traditionally believed that infection risks were highest at the femoral site (femoral > internal jugular > subclavian), arterial puncture risk highest at femoral site (femoral > internal jugular > subclavian), and pneumothorax risk higher at subclavian than at internal jugular vein site. Adoption of standardized techniques in line insertion has been shown to reduce rates of line-associated infections, and these protocols include hand hygiene, use of chlorhexidine skin prep, full barrier precautions and full body draping, avoidance of the femoral site, strict maintenance of sterile ield during insertion, and removal of catheters when no longer necessary (rather than routine exchange of catheters). In summary, risks of arterial puncture and line-associated infection are highest at the femoral site for line insertion. No beneit has been demonstrated for prophylactic changes of the ventilator circuit tubing. Oil of wintergreen (methyl salicylate) is a plant product that has been used in topical pain relief products and as a flavoring in small doses. Salicylate is the major metabolite of methyl salicylate, and one teaspoon of this substance contains approximately 7 g of salicylate, which is approximately equivalent to 23 tablets of 325 mg aspirin. Thus ingestion of 60 mL of oil of wintergreen likely has resulted in salicylate toxicity in this patient. Consistent with salicylate toxicity is the presence of an anion-gap metabolic acidosis and a respiratory alkalosis. Other features of salicylate intoxication can include lethargy, depressed mental status, tinnitus, noncardiogenic pulmonary edema, hepatic failure, and coma. In addition to supportive care, treatment for salicylate toxicity includes alkalinization of the urine to increase renal clearance of the drug and hemodialysis in severe cases of toxicity. In summary, salicylate intoxication classically presents with a combined anion-gap metabolic acidosis and respiratory alkalosis. Patients with severe asthma usually exhibit ele vated airways resistance with reasonably conserved lung compliance, and option A is the only choice with this combination. Resistance and compliance are calculated using a plateau pressure measured at end inspiration (in a patient not actively exhaling against the ventilator). In summary, patients with obstructive lung diseases (such as asthma or chronic obstructive pulmonary disease) often exhibit an increased resistance, whereas patients with diseases predominantly afecting the alveolar space (such as pneumonia or congestive heart failure) may exhibit reduced compliance. Resistance and compliance can be calculated from the ventilator with use of an endinspiratory pause to measure the Pplat (see previous equations). Increasing the respiratory rate will likely worsen gas trapping with a further reduction in exhalation time. Neurologic symptoms often develop after respiratory symptoms and can include confusion, lethargy, sei zures, and focal deicits. In summary, consider fat embolism syndrome in patients who develop respiratory failure, mental status changes, and a petechial rash in the 24-hour to 72-hour window after long-bone fracture. Treat ment includes discontinuation of unfractionated hepa rin and initiation of a direct thrombin inhibitor such as argatroban. Solely stopping unfractionated heparin will not be suicient to treat the thrombosis. Transfusing platelets is not advised, given the theoretical risk of worsening thrombosis. Transition to longer-term warfarin (with at least 5 days of overlap with a direct thrombin inhibitor) should be considered only once the platelet count has recovered and once the patient has been stably anticoagulated on a direct thrombin inhibitor. Inadequate luid resuscitation can result in the development of acute tubular necrosis, and there is concern that volume depletion can worsen the pancreatic microcirculation and further aggravate pancreatic necrosis. In summary, patients with necrotizing pancreatitis require aggressive luid resuscitation and close monitoring, given third-space luid and intravascular volume depletion. Beneicence means that the physician ought to do and promote good and must remove evil or harm. Physicians must refrain from providing interventions that are more likely to be of harm than beneit. Contraindications to noninvasive ventilation use include cardiac/respiratory arrest, inability to protect the airway, copious secretions, altered mental status, facial trauma/deformity, and high risk of aspiration. Altered mental status, copious secretions, and signiicant aspiration risk are contraindications to use of noninvasive ventilation. In summary, early source control, appropriate antibiotics, and early targeted luid resuscitation in patients with sepsis are key management strategies. Although phenylephrine has sole alpha-adrenergic activity, inotropes (such as dobutamine) act to increase cardiac contractility predominantly through beta-1 adrenergic receptors. Omeprazole signiicantly reduced the need for endoscopic therapy at the irst endoscopy (primary endpoint), as well as length of hospital stay and the number of actively bleeding ulcers (secondary endpoints). In summary, high-dose omeprazole infusion before endoscopy reduced the need for endoscopic intervention and accelerated resolution of signs of bleeding. Interestingly, a more recent study did not ind that targeting a temperature of 91. Because cooling can induce a coagulopathy, there is concern for inducing therapeutic hypothermia in patients with active bleeding, especially if they are hemodynamically unstable and are bleeding from a noncompressible site. Once the glucose level falls below 200 mg/dL, it is advised to add D5 to the administered luids. She feels well; hypertension is the only medical problem identiied in her history. Her physical examination is normal, and routine laboratory studies (complete blood count and chemistry proile) are likewise normal. Obtain three induced sputum samples, and await the results of mycobacterial culture and smear. In a 65-year-old construction worker with a longstanding history of asbestos exposure, which of the following indings/diagnoses suggests that his lung disease is unrelated to his asbestos exposure Fibrocalciic parenchymal disease, predominantly involving the upper zones of the lung B. A 65-year-old woman with a 60-pack-year history of cigarette smoking presents with cough and shortness of breath. She reports an increase in her usual amount of sputum production with yellow discoloration of the sputum. Based on the history and Gram stain, an appropriate choice of antibiotics would be which of the following Which of the following outcomes can one expect from an outpatient pulmonary rehabilitation program in a patient with severe chronic obstructive pulmonary disease A complete blood count reveals pancytopenia with a white blood cell count of 400 cells/L, hematocrit of 24%, and platelet count of 12,000/L. A sample of induced sputum is obtained; Gram stain shows no polys or microorganisms. Which diagnosis its best with the following set of arterial blood gases obtained with the patient breathing air: Po2 40 mm Hg, Pco2 80 mm Hg, and pH 7. A 60-year-old man was recently seen in the emergency department following a fall from a ladder. No other nodules were seen, and no abnormal hilar or mediastinal lymph node enlargement was found. A 56-year-old man presents with a 6-week history of nonproductive cough, moderate exertional dyspnea, and intermittent low-grade fevers (to 100. He had been in good health but smoked a pack of cigarettes each day for the last 35 years. Chest examination reveals inspiratory crackles in the lower posterior lung zones bilaterally and no wheezing. Laboratory studies include the following: hematocrit 34%; white blood cell count, 11,100/L with 18% lymphocytes, 64% polys, 7% bands, 6% monocytes, and 5% eosinophils; platelets 250,000/L. Leukotriene receptor antagonists such as montelukast (Singulair) are indicated in patients with mild or moderate disease. Antibiotics are generally indicated for exacerbations of the disease when the patient reports cough and discolored sputum. A deinitive infectious pathogen has been identiied as the cause Questions 20 to 24. She had no previous skin testing but has been tested now because her husband has just had active tuberculosis diagnosed after a 6-month illness. A pneumonia localized to the anterior segment of the upper lobe is unlikely to be tuberculosis. What is surprising in the brief description of her condition, and what may cause some doubt about the correct answer, is that she is asymptomatic, free of cough, sputum production, fever, or weight loss. Do not let this observation dissuade you from the possibility that she has active pulmonary tuberculosis. She may develop a cough any day, and the risk of contagion is real, especially in a nursing home residence where she will likely be in contact with a vulnerable population of people, many with chronic illness. With active tuberculosis as a possibility, your proper management plan is to attempt diagnosis (such as with analysis of sputum induced by inhalation of nebulized hypertonic saline or with bronchoscopy with bronchoalveolar lavage) and, while awaiting the results of sputum acid-fast stain and culture (possibly with nucleic acid ampliication to detect Mycobacterium tuberculosis and primary rifampin resistance), initiate therapy for presumed active tuberculosis (answer D). A three-drug regimen of antituberculous medications, such as ofered in answer D, is appropriate if she is a patient at low risk for primary drug-resistant tuberculosis. Watchful waiting, as in answer A, puts both the patient and those around her at risk. Until you are certain that this patient does not have active pulmonary tuberculosis, it would be inappropriate to treat with a single antituberculous medication for latent tuberculous infection (answer B). Waiting several weeks without initiating antituberculous therapy (answer C) again places the patient at risk for worsening disease and those around her at risk for acquiring tuberculous infection.

Other presenting symptoms include gynecomastia or sequel from metastases essential oils for arthritis in dogs purchase diclofenac amex, such as back/lank pain arthritis medication starting with t buy diclofenac cheap. When a suspicious testicular mass is detected on physical examination arthritis qualify for disability order diclofenac once a day, the irst diagnostic test to order is a testicular ultrasound arthritis pain feels like purchase diclofenac 100mg without prescription. Ultrasound is speciic for tumor and can distinguish a solid mass from other conditions such as hydrocele or epididymitis rheumatoid arthritis x ray purchase diclofenac 75mg mastercard. Observation is often recommended in this setting because metastatic recurrences are reliably salvageable with chemotherapy arthritis eye pain generic diclofenac 50mg overnight delivery. Men with metastatic disease are stratiied into good-, intermediate-, and high-risk categories based on sites of metastases and tumor marker levels. Alternative regimens are available for patients with compromised pulmonary function who are at increased risk of bleomycin-induced lung injury. For men who recur after chemotherapy, cure is less likely, but salvage therapies, including autologous stem cell transplant, can meaningfully prolong survival. Recurrence after 2 years is exceedingly unlikely, and routine follow-up for recurrence can be discontinued after 5 to 10 years. Adenocarcinoma of the prostate was detected in 2/12 prostate needles cores, both in the left lobe of the gland, involving 5% of each of the two cores. A 56-year-old presents to his primary care physician with a cough and productive sputum. Radical prostatectomy followed by radiation therapy to all visible sites of disease C. A 69-year-old smoker presents to her primary care physician with recent onset hematuria. Biomarkers in prostate cancer surveillance and screening: past, present, and future. Systemic, perioperative management of muscle-invasive bladder cancer and future horizons. Patient-reported outcomes after monitoring, surgery, or radiotherapy for prostate cancer. A variety of mutations can occur in either the stem cell or in a more committed cell, which result in excessive proliferation, failure of diferentiation, or both. An estimated 333,975 people are currently living with leukemia in the United States (National Cancer Institute, 2013). Blast transformation is a form of acute leukemia and manifests with weight loss, manifestations of anemia and thrombocytopenia, fever, bruising, and abdominal pain. In contrast to acute leukemia, there is no defect in maturation, so the cells mature normally and carry on their speciic functions without compromise. If untreated, new mutations will be acquired that result in failure of diferentiation and transformation into acute leukemia. Hydroxyurea is a palliative therapy, not a remission-inducing agent, primarily used to control progressive leukocytosis. On the other hand, interferon- is a remission-inducing agent, although only a minority of patients enter remission. Young patients (<50 years) with fully matched donors transplanted in stable phase generally do the best. It is administered orally and may be associated with luid retention, rash, or nausea, but most people tolerate it very well. Disease response to treatment is evaluated at the hematologic, cytogenetic, and molecular level. Most responses occur within 30 days of starting therapy, and 95% of patients in chronic phase will have a clinical response. Major cytogenetic responses are more likely to occur in patients with less advanced disease. In fact, an early response (faster and deeper) at 3 months predicts for a 3-year overall survival of >96%. It is a disease of aging, and the incidence increases in individuals over 65 years of age to as many as 25 cases per 100,000 per year. When possible, there should be consideration for treatment on a clinical trial because there has yet to be an optimal therapy for the older patient population. Reasons for the poor results in the older cohort include poor stem cell reserve, comorbid disease, and intrinsic resistance to chemotherapy marked by adverse risk cytogenetics. For patients <60 years of age the complete remission rate is approximately 70%, with an overall survival of about 30%. However, for patients >60 years of age, the remission rate is only 45% and the survival rate is 10%. Cytogenetics and molecular markers are critical determi nants of outcome in younger patients. For instance, in the presence of t(15:17) or t(8:21) there is a 60% to 80% long term diseasefree survival, whereas monosomy 7 results in a <10% longterm diseasefree survival. Males are slightly more afected than females, and African Americans have a 60% lower risk. Diagnosis Usually signs and symptoms are associated with bone marrow failure: pallor, fatigue, mucosal bleeding, bruising, or fever and infection. Leukemic iniltrates of the meninges are common, although usually later in the course. Typical leukemic blast morphology is supplemented by low cytometry, cytogenetics, and molecular analysis. Chromosome abnormalities include hyperdiploidy and hypodiploidy as well as speciic translocations. Patients who have t(9;22) are treated with imatinib or dasatinib in addition to intensive chemotherapy. Therapy hose patients who are asymptomatic and who have better prognosis disease. In general, treatment is indicated when there is progressive lymphadenopathy or hepatosplenomegaly, disease-related symptoms, or autoimmune hemolytic anemia or thrombocytopenia unresponsive to corticosteroids. Fludarabine-based therapy has largely replaced chlorambucil (Leukeran) as the mainstay of treatment. However, chlorambucil is inexpensive, nontoxic, and easy to administer, making it appealing for some elderly patients. Bendamustine (Treanda), an alkylating agent, has shown high response rates in combination with chlorambucil and with rituximab (Rituxan). Other patients may have some combination of lymphadenopathy, splenomegaly, anemia, thrombocytopenia, and hypogammaglobulinemia. Examination of the blood reveals mature-appearing lymphocytes, although some cells will be damaged in processing the slide resulting in "smudge cells. Ibrutinib (Imbruvica), an irreversible inhibitor of Bruton tyrosine kinase that targets the B-cell receptor signaling pathway, has signiicant monotherapy activity in patients with del(17p), who are poor risk. Both ibrutinib and idelalisib-based treatments induce response in patients in whom chemoimmunotherapy has failed. Patients must be monitored for tumor lysis syndrome when initiating venetoclax because of a rapid reduction in tumor volume. Coombs-positive hemolytic anemia and/or immune thrombocytopenia occur in about 20% of patients. Failure of immune surveillance results in an increased risk of solid tumors such as skin and colon cancers. Moreover, transformation to large cell lymphoma (so-called Richter transformation) occurs in 15% of patients. It is heralded by increasing lymphadenopathy, hepatosplenomegaly, fever, abdominal pain, weight loss, anemia, and thrombocytopenia with a rapid rise in lactate dehydrogenase, and it has a poor prognosis. Patients with hairy cell leukemia often have symptoms related to marrow depression with little in the way of leukocytosis, although characteristic hairy cells are usually seen in the blood. Treatment is indicated in the setting of massive or progressive splenomegaly, serious cytopenias, recurrent infections, or bulky lymphadenopathy. Prognosis Younger patients with stage 0 disease or good prognosis chromosomes often have a survival that is similar to an age-matched population. Patients with more advanced disease may have a median survival of 6 to 7 years, whereas patients with the most aggressive forms have a median survival of 1 to 3 years. Prognosis is related to staging, but cytogenetic abnormalities as established by luorescence in situ hybridization have proven to be more helpful. Normal karyotypes and trisomy 12 are the next most common and have intermediate outcomes. Deletions of 17p or of 11q as well as complex abnormalities have the worst outcome but fortunately are least common as well (see Table 14. A frequent cause of morbidity and mortality is infections related to hypogammaglobulinemia. He had been playing touch football but felt that the bruising was unexpectedly severe. Physical examination conirmed several 5- to 10-cm ecchymoses on the arms and legs including bruises on the medial surfaces. Postviral immune thrombocytopenic purpura is the most likely diagnosis, and a course of prednisone is warranted. A 70-year-old man is found to have an enlarged spleen (5 cm below the costal margin) on routine annual evaluation. He has been feeling well, although on close questioning may have lost 5 pounds in the last 6 months, and he has had a few episodes of night sweats. Cytogenetic analysis of the bone marrow is unlikely to provide useful information. Six months later, she reports having fatigue with gradual, increased shortness of breath and pleuritic chest discomfort. Perform an infectious workup, and immediately start intravenous antibiotics because she is at high risk for bacterial infections. A stat referral to cardiology for cardiac catheterization because she is at high risk for a myocardial infarction. A chest x-ray and consideration of diuretics plus supportive care for suspected pleural efusion. Longterm outcome of a pediatricinspired regimen used for adults aged 1850 years with newly diagnosed acute lymphoblastic leukemia. Central lymphoid organs are the sites where immature lymphoid cells develop into mature B and T cells; these sites are the bone marrow (for Bcell devel opment) and the thymus (for Tcell development). Mature B and T cells exit the bone marrow and thymus, respectively, and migrate to the peripheral lymphoid organs. Somatic hypermutation of mature rearranged Ig genes further modiies the repertoire of antigenic speciicities in activated B cells. Within each lymph node a ibrous capsule surrounds a central parenchyma, which is divided into an outer cortex, a paracortex, and an inner medulla. Central lymphoid organs (red) are the bone marrow, where B-cell development occurs, and the thymus, where T-cell development occurs. Features suggestive of malignancy include nodesthatare>1cmindiameter;haveairm,rubbery consistency; are ixed or immobile; are nontender to pal pation; are located in the posterior cervical, supraclavicu lar, or epitrochlear chains; or are difusely distributed. Oral petechiae may indicate thrombocyto penia or disseminated intravascular coagulation. In select cases, low cytometry may be performed to evaluate for circulating monoclonal lymphoid popula tions. Creatinine and liver function tests assess for end organ damage caused by lymphomatous iniltration. Calcium, potassium, phosphorus, and uric acid assess for tumor lysis, which may be seen with aggressive or highly aggressive lymphomas. In patients with mul tiple enlarged peripheral lymph nodes, supraclavicular nodes have the highest diagnostic yield, followed by cer vical or axillary nodes. Inguinal nodes are of low diagnos tic utility because their enlargement is often reactive. Because of the small size of tissue obtained, diagnostic ability is reduced with core needle biopsy as compared with excisional biopsy. These translocations place c-myc protooncogene (chromosome 8) next to the enhancer elements of the lg heavy chain (chromosome 14), light chain (chromosome 8), or light chain (chromosome 22). This generates a tyrosine kinase that is the molecular target of imatinib (Gleevec). Individual lymphoid and nonlymphoid cells are observed for malignant characteristics such as irregular shape, uniform or monotonous appearance, or nucleoli. Immunophenotyping may be per formed by immunohistochemistry or low cytometry; these techniques measure binding of antibodies directed against speciic molecular targets. T Lymphoblastic Leukemia/Lymphoma T lymphoblastic leukemia/lymphoma is the Tcell counter part to B lymphoblastic leukemia/lymphoma and is treated similarly. B lymphoblastic leukemia/lymphoma is more common in children but may present in older adults.

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