Linda Cardozo MD FRCOG

• Professor of Urogynaecology, King? College Hospital, London

The hallmark of nephrotic syndrome is severe proteinuria gastric spasms order 500mg methocarbamol with amex, most reliably diagnosed using a 24-hour urine collection spasms right side under rib cage generic 500 mg methocarbamol with amex. Spot urinalysis is also informative and reveals +3 to +4 proteinuria (300 to 1000 mg/dL) spasms lower left side cheap methocarbamol 500 mg mastercard, with a specific gravity usually greater than 1 back spasms 32 weeks pregnant purchase 500mg methocarbamol amex. Because of the hypoalbuminemia spasms near heart discount methocarbamol 500mg line, hypocalcemia is often seen spasms calf muscles generic methocarbamol 500mg with visa, with calcium levels less than 9. Hyponatremia and hyperkalemia can be seen, with hyperkalemia developing in patients who are oliguric. Renal biopsy is not necessary for the child with newly diagnosed nephrotic syndrome and the initial treatment will be the same, regardless of the cause. If the response is good and renal function is normal, the diagnosis of minimal change disease may be presumed. If relapses respond to corticosteroids and there is no proteinuria during disease free periods, this diagnosis is strengthened. Biopsy is generally obtained in cases where there is poor or no response to corticosteroids, the patient is less than 1 year old (high likelihood of congenital nephrotic syndrome) or over 10 years old, secondary nephrotic syndrome is suspected, there is corticosteroid toxicity, or the use of a cytotoxic agent is being considered. Patients with low serum complement levels or hypertension on presentation may require biopsy since these conditions are not characteristic of minimal change disease and may indicate other renal lesions. The treatment of primary idiopathic nephrotic syndrome of childhood is corticosteroid therapy and supportive care. Many patients may be treated on an outpatient basis, although the newly diagnosed patient is sometimes admitted for diagnostic and educational purposes. Edema is managed with sodium restriction (the "no added salt diet") and diuretics such as hydrochlorothiazide. If hypokalemia develops, an oral potassium supplement or spironolactone may be added. Aggressive use of loop diuretics may be harmful since most patients initially presenting with nephrosis are hypovolemic. Patients need to monitor their weight closely and consume adequate amounts of protein. Conditions that require immediate attention and hospitalization are severe scrotal edema, dehydration (more than 10% dehydrated), respiratory compromise due to pulmonary edema or pleural effusions, and peritonitis or suspected bacterial infection. Despite their edematous appearance, most patients have decreased intravascular volumes. Therapy is aimed at the restoration of intravascular volume and preventing volume overload. Intravenous fluids are used, sometimes with the infusion of albumin to increase the serum oncotic pressure. The albumin must be given slowly, over 8-12 hours, to prevent fluid overload from rapid intravascular volume expansion. There is some debate over the use of albumin, since the effect seems to be transient and it is presumably excreted rapidly (1). Once the intravascular volume is restored, diuretic therapy is used to mobilize the fluid and prevent volume overload. Paracentesis is performed if there is respiratory compromise secondary to severe ascites. Antibiotic therapy to cover for the most common pathogens should be started if there is evidence of bacterial infection (discussed below). Minimal change disease is characteristically responsive to corticosteroid therapy and once the diagnosis is confirmed with laboratory testing, steroid therapy should be started. Prednisone is initiated with a dose of 60 mg/sq-meter/day or 2 mg/kg/day divided in 2-3 doses. Regardless, the corticosteroids are continued and then tapered over the course of 3-6 months. In patients with minimal change nephrotic syndrome, approximately 98% will eventually have satisfactory therapeutic responses. This disease is one of frequent relapse, with two thirds of patients having a single relapse and roughly one third experiencing repeated relapses over many years. Most patients with steroid-responsive nephrotic syndrome will continue to have relapses until they are in their late teens. With repeated relapses or severe steroid toxicity (growth retardation, elevated blood pressure), cytotoxic agents such as cyclophosphamide are added to a lower corticosteroid dose. This agent has been shown to prevent relapses and to increase the duration of remission. Chlorambucil and less commonly cyclosporine have also been used for remission induction. The most common complications of nephrotic syndrome are bacterial infection and thromboembolism. There are also complications secondary to medications such as the gastric irritation and insulin resistance seen with corticosteroids or the hemorrhagic cystitis, sterility and leukopenia seen with cyclophosphamide. The tendency to develop infections, especially "primary peritonitis" (a type of pneumococcal sepsis), is thought to be due to IgG excretion, decreased complement function, and diminished splanchnic blood flow. The organisms causing peritonitis are most commonly Streptococcus pneumoniae and Escherichia coli. Peritonitis should always be considered in a patient who has nephrotic syndrome and abdominal pain or fever. Antibiotics such as ampicillin or vancomycin with a third generation cephalosporin or an aminoglycoside would provide good empiric coverage. Other infections such as sepsis, cellulitis, pneumonia and urinary tract infection are also seen. The signs of infection may be masked if the patient is currently on corticosteroid therapy. Any child with nephrotic syndrome and a fever must be thought of as having an infection until proven otherwise, since they are at high risk for sepsis, similar to splenectomy patients. Venous thrombosis is most common, especially in the renal vein, pulmonary artery, and deep vessels of the extremities. In patients with refractory nephrosis, low dose anticoagulants are sometimes used. The prognosis for children with minimal change nephrotic syndrome is good, with most patients ultimately becoming disease free and living a normal life. Mortality is approximately 2% with the majority of deaths being secondary to complications such as peritonitis or thromboembolic disease. Minimal change disease or "nil disease" accounts for 80-85% of cases of primary idiopathic nephrotic syndrome in childhood. Infection, especially peritonitis and thrombosis account for the majority to nephrotic syndrome mortality. The decision to perform a renal biopsy is usually deferred until the initial course of corticosteroid is initiated, unless there are specific risk factors such as age below one or above 10, hypertension on presentation or decreased complement on presentation. Nephrotic syndrome in a child less than 1 year old may indicate congenital nephrotic syndrome and renal biopsy is often performed. Shirakawa A one month old female is brought to her pediatrician with a chief complaint of an abdominal mass. Her mother noticed the mass earlier in the week and immediately made an appointment to see the pediatrician. The mother also notes that the infant has been frequently wetting her diapers, although there is no history of fever, vomiting or diarrhea. Her physical exam is unremarkable except for a nontender 7 cm by 8 cm left-sided abdominal mass. A renal ultrasound is ordered and reveals bilateral enlargement of her kidneys with diffuse echogenicity and microcysts. The infant is diagnosed with autosomal-recessive polycystic kidney disease and a possible urinary tract infection. Her renal function is sufficient, but it is anticipated that it will worsen as she grows. Cystic kidneys in children and adolescents present in various forms and can range from a single cyst to multiple bilateral cysts. In this chapter, a few of the more common disease conditions will be discussed: multicystic dysplastic kidneys, autosomal recessive polycystic kidney disease and autosomal dominant polycystic kidney disease. Other cystic kidney diseases that will not be discussed include nephronophthisis (a common genetic cause of chronic renal insufficiency in children which presents with polyuria and polydipsia, anemia and growth retardation), medullary cystic disease (autosomal dominant disease in which young adults develop renal failure), medullary sponge kidney (dilated intrapapillary collecting ducts and multiple small cysts that usually presents in adulthood), glomerulocystic kidney disease (seen in a variety of inherited syndromes), simple renal cysts (incidental findings that generally do not impair renal function), multilocular cysts (unilateral benign tumor), acquired cystic kidney disease (occurs in patients with renal failure), and syndromes with cystic kidneys (such as tuberous sclerosis, Meckel syndrome, and von Hippel-Lindau disease). The classic type contains multiple cysts of various size, with an abnormal renal shape and an atretic proximal ureter. The hydronephrotic type is rarer and consists of peripheral cysts that communicate with a large central cyst with a dilated pelvis and calyces (1). The most recent studies estimate that the incidence is 1 in 2400 livebirths, and it is more common in males (1,2). The disease usually occurs unilaterally, but can be seen bilaterally in as many as 20% of cases (2). The first proposes that abnormal induction of the metanephric blastema leads to dysplasia of the renal parenchyma that is non-uniform, resulting in cysts that increase in size and eventually compress normal renal tissue (1). In unilateral cases, there is a compensatory hypertrophy in the contralateral kidney. Other possible but rare presentations include urinary tract infection, abdominal pain, hematuria, hypertension, and compromised respiratory function (1,2). There is also an association with contralateral ureteropelvic junction obstruction (1). Other major anomalies can be seen in the cardiac, respiratory and gastrointestinal systems (1). Bilateral cystic kidneys are usually not compatible with life due to oligohydramnios and result in either stillborn babies or newborns requiring dialysis at birth (2). Hydronephrosis usually retains a reniform shape and shows apparent renal parenchyma around a central cyst (1). Hydronephrosis also retains communication of the cysts with the collecting systems (2). Autosomal dominant polycystic kidneys are usually bilaterally enlarged while autosomal recessive polycystic kidneys are generally small with a hyperechoic pattern. It is recommended to obtain sonography and perform a voiding cystourethrogram within the first 48 hours of life. Radionuclide studies are also performed after 1 month of age to determine renal functioning. Since most cases are asymptomatic, nephrectomy is not always performed and instead close follow-up is maintained. Ultrasound is performed every 3 months up to 1 year of age and then every 6 months up to 5 years of age. Nephrectomy is usually performed only if the child is symptomatic or the parents choose surgery after understanding the benefits and risks. In 73% of cases, the cysts decrease in size, with a 40% complete resolution rate (1). Uncommonly, children may have pain, infection, or hypertension and even rarer is the possibility of malignant degeneration into a Wilms tumor (1). In the 5% to 17% of cases that are bilateral, newborns generally do not survive and if they do, they require dialysis immediately (1). The kidneys are enlarged, while retaining their normal shape and have a spongy appearance. Three factors have been shown to contribute to the formation of renal cysts and their subsequent enlargement. The first factor is that tubular hyperplasia is present in all cystic diseases and contributes to cystic expansion (5). Second, secretion of tubular fluid leads to the accumulation of intratubular fluid and progressive enlargement (5). Third, abnormalities in extracellular matrix interactions appear to have an effect on cell growth and can lead to abnormal epithelial hyperplasia and secretion (5). Many cases are seen prenatally on ultrasound with oligohydramnios and large renal masses (5). Other presentations include enlarging abdominal masses, respiratory problems due to limited diaphragm mobility (or pulmonary hypoplasia), failure to thrive due to enlarged kidneys, proteinuria, pyuria, hypertension due to fluid overload, and urinary tract infections due to vesicoureteral reflux (4). Children eventually develop chronic renal failure and end-stage renal disease with associated electrolyte imbalances of hyperkalemia and hyperphosphatemia (4). Liver abnormalities may present as signs of portal hypertension such as esophageal varies, hepatomegaly, and spider nevi. Ultrasound is the diagnostic test of choice, although an intravenous pyelogram will also show enlarged kidneys (4). On renal ultrasound, there is increased echogenicity with a possible hypoechoic rim (4). Hypertension should be treated with medications, although it may be difficult to control. Urinary tract infections should be properly diagnosed and treated with antibiotics. Chronic renal failure and end-stage renal disease are treated by managing electrolyte abnormalities, anemia, and renal osteodystrophy, with eventual dialysis and transplantation (4). Nephrectomy may be an option if there are respiratory problems and/or feeding problems due to compression (4). Studies show that about 46% are alive at 15 years of age and those that survive through the first year of life have an even higher survival rate (79% alive at 15 years) (5). It is characterized by renal cysts in various locations and extrarenal manifestations in the gastrointestinal and cardiovascular systems. The variability in cyst formation and disease severity depends on the locus affected and how much protein is being made. Symptomatic children typically present in late childhood or adolescence with any of the following: hematuria, hypertension, abdominal or flank pain, abdominal mass, urinary tract infection, or proteinuria (4). The third pediatric presentation is severe neonatal disease that is frequently fatal. These neonates usually die from respiratory failure but they may also die of renal failure during the first year of life (4).

Utilizing history and physical exam information spasms medication buy methocarbamol 500 mg line, it is important to classify the shock syndrome into one of 3 major etiologies: 1) hypovolemic shock muscle relaxant tinnitus cheap methocarbamol 500mg with mastercard, a) absolute zma muscle relaxant generic methocarbamol 500 mg line, b) relative muscle relaxant topical discount methocarbamol 500mg otc, 2) septic shock spasms and spasticity methocarbamol 500mg low cost, or 3) cardiogenic shock spasms 1983 imdb order 500mg methocarbamol otc. A loss of circulating blood volume results in decreased preload (the fuel) with resultant decreased cardiac output. Absolute hypovolemia has three major causes; 1) dehydration secondary to a) diarrhea and vomiting or b) poor intake; 2) hemorrhage or 3) renal losses of fluid from a) diabetes mellitus or b) diabetes insipidus. There are four major causes of this: 1) sepsis, 2) anaphylaxis, 3) spinal cord injury or 4) drug reactions secondary to drugs such as barbiturates, phenothiazines, and antihypertensives. Septic shock is a microcirculatory dysfunction that results from activation of a systemic inflammatory response from age-group specific bacterial pathogens. Those at risk for septic shock include: oncology patients, those with central venous (oncology) catheters, on chronic high dose steroids, or with a congenital or acquired immunodeficiency. Gram negative bacterial endotoxin-mediated septic shock results in activation of numerous mediators of circulatory failure. The end result is impaired myocardial contractility, alteration in vascular tone, and capillary leak. Lastly, cardiogenic shock (the pump) may be the primary cause of shock or a late manifestation of other forms of shock. Here, there is an abnormality in cardiac function due to depressed myocardial contractility. All patients should receive 100% supplemental oxygen by face mask, followed by the correction of the mismatch between metabolic supply and demand. Anticipation of the effects of shock as a dynamic, clinical syndrome with multi-system consequences, which can be reversed, with optimization of cardiac output is essential to prevent decompensation and irreversible shock. Treatment can be classified broadly into: 1) oxygenation, 2) vascular access, 3) fluid administration, and 4) drug therapy. Oxygenation includes providing 100% oxygen and also assuring adequate hemoglobin, stopping hemorrhage, and replacing blood if the hematocrit is less than 30%. Consider endotracheal intubation, but be aware of the cardiovascular effects that intubation and positive ventilation can cause, such as bradycardia, hypotension or reduced venous return. There are 2 major types of fluid that can be administered, crystalloid or colloid. Crystalloid is an effective volume expander in resuscitation but requires 2-4 times the volume of blood loss to restore hemodynamic parameters. Although there is less potential for edema as a result of its use, there are complications including increased serum osmolarity, increased serum Na and C1 levels, metabolic acidosis, and cerebral dehydration and hemorrhage. In addition, it can draw extravascular water into the intravascular space because of its oncotic pressure effect. Most often fluid administration in the form of volume resuscitation is accomplished by the infusion of 0. Central venous pressure monitoring will help fluid management in critical patients. General guidelines are to be liberal and aggressive with fluid resuscitation, giving 20 ml/kg initially and repeating as needed. For septic shock, more than 40ml/kg in the first hour has been shown to improve outcome. When approaching 80 ml/kg, consider the use of an inotropic agent such as dopamine or epinephrine. Pharmacologic support includes medications that: 1) augment cardiac contractility (inotropic/cardiotonic), vasoconstrictors to reverse inappropriate vasodilation, and sometimes vasodilator drugs to reduce preload and afterload in cardiogenic etiologies, 2) antibiotics (for septic shock), 3) sodium bicarbonate, 4) calcium, 5) immunotherapies, and 6) controversial therapy. However, before specific drugs are described, a review of adrenergic receptor physiology is indicated. Each receptor has a different physiologic response, as noted here: Alpha: Arteriolar constriction Beta-1: Increased myocardial contractility (inotropy) Increased heart rate (chronotropy) Beta-2: Peripheral vasodilation Bronchial smooth muscle relaxation Dopaminergic: Smooth muscle relaxation Increase renal blood flow Examples of classic agonists include phenylephrine (pure alpha), isoproterenol (pure beta, both beta-1 and beta-2), dobutamine (selective beta-1), albuterol (selective beta-2), epinephrine (both alpha and beta). Low dose (1-2 mcg/kg/min) results in vasodilation of the splanchnic (renal) and cerebral vascular beds. Mid-dose (3-10 mcg/kg/min) has primarily a beta effect (chronotropic and inotropic), while a higher dose (> 10 mcg/kg/min) has a pure alpha effect (pressor). Dobutamine has a pure beta-1 (chronotropic and inotropic) effect, the effective dose used ranging from 2-20 mcg/kg/min or greater. Examples of vasodilator drugs used for "afterload reduction" in a failing heart to ease the work of "pumping" are nitrates such as nitroprusside and nitroglycerine. Nitroprusside, infused continuously at a rate between 1-10 mcg/kg/min, is a vasodilator working on both resistance and capacitance sides of the circulation; however with time, a toxic cyanide metabolite is formed. Consider the use of sodium bicarbonate after assuring adequate volume resuscitation and ventilation, at a dose of 1-2 mEq/kg. Calcium: Hypocalcemia can occur after tissue hypoperfusion of any etiology and can result in myocardial depression and hypotension. If hypocalcemia is documented in a symptomatic patient not responding to inotropes and pressors, then consider treating the hypocalcemia. For ages less than 6 weeks, a combination of ampicillin plus cefotaxime can be used. These are beyond the scope of this chapter, but will be important adjuncts to antibiotics and intensive care treatment in the future. A more detailed description of additional medications utilized for resuscitation can be found in the chapter on pediatric pulmocardiac resuscitation. Ongoing assessment of the patient in shock includes repeated reassessments of the physical exam, and monitoring equipment including pulse oximetry, cardiorespiratory monitoring, repeated blood pressures, central venous pressure (if indicated), and urine output through a catheter. Physical exam findings will be reflected in signs of improved perfusion which will include improvement in appearance, including alertness (mental status), eye contact, skin capillary refill, color and temperature, heart rate and pulse strength, urine output, respiratory pattern and rate, and blood pressure. Resolving metabolic acidosis and declining serum lactate levels are lab findings indicating improvement of perfusion. Normal circulatory function depends on three factors: cardiac function (the pump), vascular tone (the pipes), and blood volume (the fuel). A disturbance in one or more, resulting in inadequate delivery of oxygen and nutrients to the tissues, leads to shock. After 20 cc/kg of isotonic fluid has been administered without clinical response c. After 60 cc/kg of isotonic fluid has been administered without clinical response. After isotonic fluid administration has resulted in inadequate clinical response and the patient requires operative repair 4. Which circulatory finding is the hallmark of the diagnosis of late (decompensated) shock? Appropriate initial management for the child described in question 6 would include which of the following? Utility of an end-tidal carbon dioxide detector during stabilization and transport of critically ill children. Intraosseous infusion of fluids in the initial management of hypovolemic shock in young subjects. Textbook of Pediatric Intensive Care, Williams and Wilkins, Philadelphia 1996, pp. This represents a case of cardiomyopathy with four classic findings of congestive heart failure. Epinephrine may be used later in desperation since its alpha effect may have detrimental consequences on overall circulation. Today her parents report that she has had increased work in breathing with audible wheezing. Her weight is 8 kg (25th percentile for a 9 month old, corrected post conception age). Suspecting a plug in her tracheostomy, her tracheostomy tube is suctioned and then changed when there is some resistance to passage of the suction catheter. She is bag ventilated via her tracheostomy and subsequently placed on mechanical ventilation. In evaluating this child, multiple etiologies had to be considered, including problems with the tracheostomy. A plugged tracheostomy tube must always be considered as the cause of respiratory distress in a child with a tracheostomy. There are multiple etiologies of respiratory distress, and the treatment obviously depends on the cause. The goal is to recognize the early signs and symptoms of respiratory problems, intervene early, and hopefully prevent progression to respiratory failure. Basically, respiratory failure is the inadequate ventilation and oxygenation, resulting in hypercarbia and hypoxemia severe enough to require ventilatory assistance. Evidence of respiratory failure includes cyanosis, tachypnea, apnea, slow respiratory rate, retractions, poor aeration, and appearance of fatigue. She exhibited another common feature of respiratory failure, which is that she failed to adequately oxygenate despite maximal supplemental oxygen by mask. This can be easily assessed by monitoring the pulse oximeter readings while maximal supplemental oxygen by mask is administered. Note that in our case, the diagnosis of respiratory failure was made without obtaining a blood gas. Eventually in the therapy of a child with respiratory failure, blood gases will be helpful in managing therapy. There are many etiologies of respiratory failure including neurologic disorders, respiratory infections and foreign bodies. Managing the airway, supplying oxygen and assuring adequate ventilation are the goals regardless of the etiology. Specific treatments, however, depend on determining the location and cause of the respiratory distress. Given the limited scope of this chapter, only a few of the more common disorders will be described and their therapies outlined. If there is evidence of upper airway obstruction, such as snoring or harsh stridor, repositioning the airway may be useful. Suctioning the naso/oropharynx may be helpful, and in certain cases airway adjuncts such as an oral airway or nasopharyngeal tube may be necessary. Upper airway problems are generally manifested by stridor and include epiglottitis, croup, laryngomalacia, vocal cord problems and airway foreign bodies. Page - 484 Epiglottitis has become much less common since the wide spread use of the Haemophilus influenza B vaccine. Epiglottitis is characterized by high fever, a toxic appearance, drooling and a muffled voice. Croup is much more common, occurs predominately in infants, and is characterized by a barking or seal-like cough, stridor and low grade temperature. Laryngomalacia, vocal cord problems and foreign body aspiration are generally diagnosed by history and laryngoscopy/bronchoscopy. Oxygen is always an appropriate initial therapy, offered in the least threatening manner. Intubation may be required acutely for severe laryngomalacia and vocal cord dysfunction. Foreign body aspiration should be suspected in a previously healthy child with the acute onset of respiratory distress. Bronchoscopy and removal of the foreign body are usually the only therapy required for aspirated objects. In some cases where bronchospasm and airway swelling accompany the aspiration, bronchodilators, epinephrine aerosols and corticosteroids may be indicated. Neurologic conditions that lead to respiratory failure, in contrast to airway or pulmonary problems, are not usually associated with signs/symptoms of respiratory distress. Level of consciousness may be impaired, depending on the cause, but this may be difficult to assess due to muscle weakness. If the etiology is a sedative or narcotic overdose, oxygen and a reversal agent such as naloxone or flumazenil may be all that is necessary. For longer term conditions such as Guillain-Barre or botulism, intubation and mechanical ventilation are usually required until the neurologic problem resolves. Central hypoventilation and spinal cord injuries frequently result in the need for tracheostomy and long term ventilation. Reactive airway disease, characterized by distal airway swelling, increased secretions and airway constriction is a common cause of respiratory distress/failure. Corticosteroids are most helpful in those with a prior history of reactive airways disease. Frequently they will be on chronic bronchodilators and nebulized corticosteroids or steroid inhalers. It is important to ask this history since children on corticosteroids recently may be adrenal suppressed and require stress dose (high dose) corticosteroids with acute illnesses. The use of heliox and magnesium have been reported to be useful in some patients, but are not yet considered standard therapies. Helium/oxygen mixtures have a lower density than nitrogen/oxygen (room air) mixtures and therefore flow with less turbulence. Magnesium is a smooth muscle relaxant and has been reported to be useful for severe asthma by some investigators. Pneumonia reduces lung compliance and increases ventilation perfusion (V/Q) mismatching due to lung injury and filling of the alveoli. Treatment of the child with pneumonia and respiratory failure may include oxygen, antibiotics (if a bacterial process is thought to be present), chest physiotherapy to help open atelectatic areas and promote drainage, and mechanical ventilation. The disease involves alveolar filling as well as interstitial edema and infiltration with cells and fibrosis. Treatment includes tracheal intubation and ventilation, usually with "permissive hypercapnia" techniques to reduce barotrauma.

Consequently spasms back pain and sitting methocarbamol 500 mg cheap, it is not always possible to study exposure to prescription drugs as soon as they are available on the Canadian market muscle relaxant neck pain generic methocarbamol 500 mg without prescription. As well muscle relaxant with ibuprofen discount methocarbamol 500 mg online, there is no centralized computer database on inpatient drug use muscle relaxant agents cheap methocarbamol 500 mg fast delivery, over-thecounter drug use muscle relaxant and painkiller order methocarbamol 500mg visa, or use of alternative therapies muscle relaxant pills over the counter purchase methocarbamol 500 mg online. Diagnostic information is derived primarily from hospital separation or physician billing data. As well, if the outcome does not result in hospitalization, the diagnostic information is weaker because it is based on physician billing data, which have less complete and less specific diagnostic coding. The lack of a complete, centralized laboratory information database limits the ability to detect outcomes that must be identified and=or confirmed by specific test results. The databases do not contain information on some potentially important confounding variables. Study designs must consider alternative methods of obtaining the necessary information on confounding factors. Some of these limitations may be offset by the ability to access individual patient records to obtain information not included in the computer databases. This is a manual process, however, and is therefore more time consuming and expensive. Policies and procedures are in place that enable the data to be used for research while maintaining beneficiary and provider confidentiality and database integrity. Researchers using the data have included those from academia, other governments, the pharmaceutical industry, other private companies, and practitioners. The prime consideration for use of the databases is confidentiality of both recipients and providers of services. Identifiable information including, for example, the identity of the patient, physician, pharmacy, or hospital will not be released. As well, Saskatchewan Health will not allow source files, even if pseudo-identified, to be released; only aggregated information or limited fields of information at a person level may be released. Further, information collected directly from study subjects will not be linked with the administrative data without the explicit consent of the study subjects. The Research Services Unit of the Population Health Branch has responsibility for conducting and=or facilitating pharmacoepidemiology and other outcomes research, and is the point of contact for investigators who are interested in using the data for research. Personnel in the Unit have combined expertise in project management, research methodology, and analyses as well as extensive experience in using the large computerized databases for pharmacoepidemiology and epidemiology research. Metformin, a biguanide oral antihyperglycemic agent, was a recent new chemical entity in the United States, but had been on the market in Canada since 1972 and listed in the Saskatchewan Formulary since 1981. Subject selection, based on information in the outpatient prescription drug database, identified 11 797 beneficiaries who received one or more prescriptions for metformin, for 22 296 person years of exposure. An incidence rate of nine cases per 100 000 person years (95% confidence interval (0, 21)) was calculated based on the person years of exposure and two cases of lactic acidosis with substantiating lactate levels. One case had a possible spurious laboratory value which, if discounted, resulted in an incidence of 4. This was the first known population based longitudinal (16 years) postmarketing study with complete ascertainment of patients dispensed metformin and hospitalizations associated with lactic acidosis. Because the rate of lactic acidosis in metformin users is low, this study had the advantage of having enough accumulated person time of metformin exposure for detection of cases. A study of the use of statin cholesterol lowering drugs and the risk of cancer is being conducted by Beck et al. A feasibility study was conducted to determine whether there were enough users of statins exposed to these drugs for a sufficiently long period to be able to detect an association between their use and the incidence of cancer. Based on the findings of the feasibility study, work on a historical cohort study is proceeding. Four study groups, defined based on their exposure or lack of exposure to certain lipid lowering drugs, are being identified for followup. The exposed cohort consists of those individuals identified as having received one or more prescriptions for statins during the period January 1989 to June 1997. For the breast cancer analyses, 13 592 female statin users were identified, with a total of 20 953 person years of exposure. The nonexposed comparison group was selected from the population of eligible beneficiaries who did not have any prescriptions for lipid lowering drugs during the study period. The remaining two comparison groups were selected based on their exposure to other commonly used lipid lowering drugs (cholestyramine or gemfibrozil). Use of these comparison groups will help to control for the presence of potentially confounding variables that may be associated with the use of lipid-lowering drugs. Each study member was followed until admission to hospital for a renal disorder, death, emigration from Saskatchewan, or the end of the study period. As well, information was abstracted from hospital records by trained abstractors to validate cases and to obtain other clinical information not available in the computerized databases. Controls were selected from the 228 392 members of the study population according to certain criteria. The data compiled for this research project have also been used to study several outcomes related to gastrointestinal and liver effects. A total of 45 716 individuals were identified as being diabetic in Saskatchewan during the study period. Analyses are ongoing and will include descriptions of comorbidities and investigation of drug outcomes among the diabetic cohort. The dataset will be updated regularly to enable ongoing measurement of trends in diabetes in Saskatchewan. The general methodology will be applied to other chronic diseases for broader surveillance activities. These patients were then followed for a year after their initial prescription to identify all medical ``events' experienced while on the medication. In this study, an ``event' was defined as any diagnosis or medical service recorded in the physician services or inpatient hospital databases as well as any prescription recorded in the outpatient drug data. Two of the drugs selected for this project were nonsteroidal anti-inflammatory drugs: piroxicam and sulindac. The drugs were selected because their adverse effect profiles were reasonably well known and each drug had been covered by the Saskatchewan Drug Plan for an appropriate time period. Analyses examined age, sex, patterns of treatment continuation, and diagnostic ``event' rates. The cost of using such a system is relatively inexpensive and there are no followup problems. Studies of Drug Use In Pregnancy A study was carried out as a rapid response to a report from France of a highly significant association between maternal use of valproate for epilepsy during pregnancy and spina bifida in the offspring. The drug records of the 95 valproate users were then linked to their hospitalization files via their unique identification number for the period January 1980 to June 1982, and women who had a pregnancy related admission were identified. During the study period of interest, the Vital Statistics file did not use the unique identification number, so the file was searched by name for that period to validate the births found in the hospital file and also to identify stillbirths among the 95 women. Finally, the outpatient drug histories were reviewed for the eight women to look more closely at the timing of the valproate prescriptions relative to the pregnancy. In this study, the exposed population was too small to provide sufficient statistical power to detect an association. The project did, however, demonstrate the potential of using the Saskatchewan databases to study certain effects of drugs used during pregnancy. In addition, complete review of the records was finished within eight days of the initial decision to conduct the study, illustrating the value of relatively current and linkable health databases. Study participants included all those patients who received at least one prescription for risperidone between July 1993 and December 1993. Utilization information from the databases was collected for equivalent periods (an average of 10 months) before and after initiation of risperidone therapy. The results demonstrated that treatment with risperidone produced substantial reductions in the utilization of health care services which translated to cost savings across hospital, physician, and mental health services. The Saskatchewan databases were used to examine information on care received and cost of that care as one component of a study of the cost-effectiveness of home care as a substitute for hospital care. The study was designed to provide health care providers and decision makers with information on whether this shift has affected patient health and whether it truly saves money. The results showed that about half of all adult medical and surgical patients could be discharged from hospital an average of two days sooner and that these patients could be provided with alternate care, mostly home care, to achieve the same health outcomes at less cost. The use of cholesterol testing and drug treatment for lowering blood cholesterol have grown rapidly in the past decade. The researchers found that the proportion of new users stopping medication after filling only one prescription ranged from 30 to 38%. The estimated median time on medication for these new users was 111 days, and the proportion of new users remaining on medication at one year was 25%. Drug type was the single strongest predictor of time on drug therapy with the pattern of adherence paralleling known drug side effects. For example, new users of niacin and cholestyramine were most likely to stop their medication, while those dispensed a statin were most likely to continue. The researchers concluded adherence to lipid lowering drug therapy in the Saskatchewan population was poor. The prescription drug database was used to examine recent trends in use of inhaled 2-adrenergic agonists and inhaled corticosteroids and to determine whether these trends were in keeping with widely publicized guidelines recommending a reduction in the use of agents to treat symptoms. There was a steady increase in the proportion of the population receiving prescriptions for drugs to treat asthma over the five-year period. There was also a marked change in the patterns of prescriptions for drugs used to treat asthma with a shift toward the use of inhaled corticosteroids. In contrast, the proportion of patients who received 2-adrenergic agonists remained fairly constant. The authors concluded that the trends suggest many physicians adopted current guidelines advocating increased attention to prevention of airway inflammation in the treatment of asthma. Product Assurance Evaluations the databases have been used to provide information for ``product assurance' agreements with the Saskatchewan Drug Plan. Depending on the differences between actual and expected use, an intervention may occur and a financial adjustment may be made against the manufacturer. The data (either drug data alone or in combination with other health services data) have been used to provide the information on the actual utilization and outcomes in Saskatchewan for such agreements. One of the objectives integral to this principle is the effective use and development of information, technology, planning, and reporting management systems. For example, one information system under development will support the provincial immunization program. When fully implemented, it will operate through the Internet, and data will be collected from all public health offices in the province with infants and pre-schoolers being the priority. Through the information network, health service providers would be able to access the data when authorized, examine records and tests, and consult with clients and colleagues. Collection of appropriate information and preservation of confidentiality of personal health information will continue to be of paramount importance. In 1997 and 1998, Saskatchewan Health held extensive consultations within the province on the protection of personal health information. As a result of those consultations and in order to put a legal framework around good information practices, the Health Information Protection Act was passed in the legislature in the spring of 1999 with proclamation anticipated in 2000. It will emphasize protection of privacy of personal health information while ensuring that, with proper precautions, information is available to provide efficient health services. Research under specific conditions will continue to be a permitted use of health service information. The value of the Saskatchewan health databases as a resource for pharmacoepidemiology research has been demonstrated. As enhancements of the databases continue and as the information is used in a responsible manner, the databases will continue to contribute to providing valuable information on public health issues related to drug use. We also thank our colleagues in Saskatchewan Health, in particular Margaret Baker, Jim Engel, Patrick Melia, and Valerie Phillips, for their review of the manuscript. Epidemiologic Research Using Linked Computerized Health Care Datafiles in Saskatchewan, Canada, Tecnical Report 2. Saskatoon, Saskatchewan: Psychiatric Pharmacoepidemiology Research Consortium; 1992. Hospitalization for renal impairment among users and nonusers of nonsteroidal anti-inflammatory drugs in Saskatchewan, Canada, 1983. Comparative efficacy of long-acting depot and oral neuroleptic medications in preventing schizophrenic recidivism. Fatal upper gastrointestinal hemorrhage or perforation among users and nonusers of nonsteroidal anti-inflammatory drugs in Saskatchewan, Canada 1983. Clinical complexity and epidemiologic uncertainty in case-control research: fenoterol and asthma management. Nonsteroidal anti-inflammatory drugs and gastrointestinal hospitalizations in Saskatchewan: a cohort study. Increased risk of hospitalizations for acute liver injury in a population with exposure to multiple drugs. Ongoing measurements of data quality within Saskatchewan's linkable health databases [abstract]. Validity of rheumatoid arthritis diagnoses listed in the Saskatchewan hospital separations database. Record linkage to conduct an epidemiologic study on the association of rheumatoid arthritis and lymphoma in the province of Saskatchewan, Canada. Is the association between inhaled beta-agonist use and life-threatening asthma because of confounding by severity? The Saskatchewan oral contraceptive cohort study of oral contraceptive use and cardiovascular risks. An acute adverse drug reaction alerting scheme using the Saskatchewan Health datafiles.

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Arcanobacterium haemolyticum is a rare cause of pharyngitis that usually occurs in adolescents or young adults muscle relaxants kidney failure purchase methocarbamol 500mg visa. The illness may mimic group A streptococcal infection including a scarlatiniform rash muscle relaxant homeopathic purchase methocarbamol 500mg overnight delivery. Neisseria gonorrhoeae may cause a pharyngitis if inoculated into the pharynx by oral contact with infectious material muscle relaxant medications order 500mg methocarbamol. Usually muscle relaxant uk proven methocarbamol 500 mg, the infection is asymptomatic but clinical pharyngitis and tonsillitis may develop muscle relaxant otc order 500 mg methocarbamol. The characteristic finding is the grayish brown diphtheric pseudomembrane which may involve the tonsils unilaterally or bilaterally and can extend to involve the soft palate spasms of the bladder discount 500 mg methocarbamol overnight delivery, nares, pharynx, larynx or even the tracheobronchial tree (3). Case fatality rates range from 3% to 23%, the usual mechanisms of morbidity and mortality being upper airway obstruction from extensive membrane formation and myocarditis. Edema of the soft tissues in the neck and prominent cervical and submental adenopathy may give the patient a "bull-neck" appearance (3). The disease is best prevented by Page - 189 immunization, but if necessary, is treated with equine antitoxin and antibiotics, erythromycin or penicillin G intravenously. Mycoplasma pneumoniae may cause pharyngitis, but since it is also commonly isolated from controls, the significance of such infections remains unknown. Chlamydia pneumoniae has also been reported to cause pharyngitis either by itself or preceding a pneumonia. Since routine testing does not diagnose either of these organisms, treatment is not likely to be offered. The incidence of these organisms is likely seen in only a small percentage of infections and since serious complications are not commonly observed, it is likely that these infections resolve without treatment in most instances. Acute tonsillopharyngitis precedes the formation of abscess, usually with an afebrile period noted or unresolving fever before the onset of severe throat pain. There may be trismus (pain on opening the mouth) and refusal to speak or swallow because the pain may be so intense. On exam, one of the tonsils is usually markedly swollen, with effacement of the anterior tonsillar pillar and deviation of the uvula to the opposite side. Treatment involves incision and drainage of the abscess and intravenous antibiotics. Penicillin may be used although some prefer clindamycin for better anaerobic coverage. Authorities vary on whether tonsillectomy should be performed after the initial episode (2,10). Retropharyngeal abscess can also manifest as a complication of bacterial pharyngitis or less commonly from extension of vertebral osteomyelitis or penetrating injury to the posterior pharynx. The potential space between the posterior pharyngeal wall and the prevertebral fascia contains lymphatic tissue that involutes around age 3 to 4 years, making infection less common after that age. A child with a preceding acute nasopharyngitis or pharyngitis who refuses to eat, has high fever, severe distress, hyperextension of the neck or noisy gurgling respirations may have a retropharyngeal abscess. Imaging (lateral neck radiographs) is essential to confirm the diagnosis, although in an uncooperative child, a bulge in the posterior pharynx may be seen. To obtain a proper soft tissue lateral neck x-ray, the neck should be in full extension (lordotic) and the x-ray should be taken in end-inspiration. False positive x-rays (false widening of the prevertebral soft tissue) may occur with poor positioning. Untreated retropharyngeal abscesses may rupture into the airway or spread down the fascial planes to the mediastinum. Treatment includes incision and drainage under general anesthesia and empiric intravenous antibiotics with coverage for Staphylococcus aureus until culture and sensitivity information is available (2,10). Mechanical problems such as tonsillar hypertrophy leading to obstructive sleep apnea and chronic mouth breathing may cause pharyngitis. Foreign body must always be included in the differential of sore throat that does not appear infectious. Asymmetric swelling of the tonsils without infection may be a clue to malignancy (2,11). Adult type epiglottitis should be considered in older children and teens complaining of a severe throat without much clinical findings. Diagnoses such as chronic fatigue syndrome contain sore throat as part of their criteria but continue to be controversial. The latter symptoms occur for 3 to 6 days with three weeks during which the patient is entirely well interspersed with clockwork periodicity. As one author puts it, is periodic fever an infectious disease or immune dysregulation? Pharyngitis can have a myriad of causes, but for the most part, the causes are easily managed viral infections. The physician has to have a certain awareness of the more serious problems which can present as pharyngitis and the appropriate workup and management once the diagnosis is suspected. Certain clues can help the physician diagnose the more serious causes of sore throat and treat them appropriately. He has been afebrile, has rhinorrhea, cough and one day of diarrhea associated with his sore throat. Exam shows an adherent grayish-white membrane over both tonsils and the soft palate that, when removed, leaves an edematous, bleeding area of tissue. In children, nonsuppurative sequelae of group A strep infection of the pharynx include (circle all that apply): a. Section 3-Summaries of Infectious Diseases-Diptheria, Enterovirus (Nonpolio) Infections, Epstein-Barr Virus Infections (Infectious Mononucleosis), Group A Streptococcal Infections. Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis. Her past medical history is significant for atopic dermatitis (uses topical hydrocortisone), as well as multiple visits for wheezing episodes which respond well to nebulized albuterol. A presumptive diagnosis of reactive airway disease is made, and he is discharged to home on oral albuterol and prednisone. She returns 2 days later with increased coughing and tachypnea with an oxygen saturation of 94% in room air. A presumptive diagnosis of pneumonia is made and she is admitted to a general hospital for further evaluation and management of pneumonia and asthma exacerbation. She returns to the office 3 days later with increasing coughing and hypoxia (oxygen saturation 92%). Based on her clinical presentation of hypoxia and repetitive coughing; a working diagnosis of pertussis is made. Household contacts are subsequently interviewed, and erythromycin prophylaxis is started in all contacts. After 7 days, she improves and is discharged to home to complete her course of erythromycin. Bordetella pertussis is a gram negative coccobacilli that is the cause of an acute respiratory illness initially characterized by protracted coughing. With respect to the differential diagnosis, protracted coughing can also be caused by Mycoplasma, parainfluenza or influenza viruses, enteroviruses, respiratory syncytial virus, or adenoviruses. Pertussis is extremely contagious, with attack rates as high as 100% in susceptible individuals exposed to aerosol droplets at close range. Although a person may be fully immunized, either actively or passively, the rate of subclinical infection is as high as 50%. Neither natural disease nor vaccination provides complete or lifelong immunity against reinfection or disease (1). Protection against typical disease begins to wane 3-5 years after vaccination and is unmeasurable after 12 years. In addition, pertussis incites histamine sensitivity, insulin secretion and leukocyte dysfunction. There are 3 post-incubation stages: 1) catarrhal, 2) paroxysmal, and 3) convalescent. After an incubation period from 3 to 12 days, the catarrhal stage is marked by: congestion, rhinorrhea, low-grade fever, sneezing, and lacrimation. As symptoms wane, the paroxysmal coughing stage begins which can be characterized by one or more of the following: 1) Intermittent, irritative hacking paroxysmal coughing, 2) Choking, gasping, eyes watering and bulging, 3) Occasional coughing up of mucous plugs, 4) Post-tussive exhaustion, 5) Coughing in long spasms with the face turning red, or sometimes blue. Conjunctival hemorrhages and petechiae on the upper body are common due to all the coughing, Pertussis should be suspected in a patient who complains of incessant coughing for 2 weeks, especially if nothing else shows up on the physical exam. Chlamydia trachomatis presents with purulent conjunctivitis, tachypnea, rales or wheezes. Leukocytosis (normal small cells, rather than the large atypical lymphocytes seen with viral infections) due to absolute lymphocytosis occurs in the late catarrhal and paroxysmal stages. Neutrophilia would suggest a different diagnosis or secondary bacterial infection. The chest radiograph shows perihilar infiltrates or edema and variable degrees of atelectasis. However, a false negative can occur in those who have received amoxicillin or erythromycin. A flexible swab kept in the posterior nasopharynx until the patient coughs, is one way to obtain the specimen. Those under 2 months of age have the highest reported rates of pertussis-associated hospitalization (82%), pneumonia (25%), seizures (4%), encephalopathy (1%), and death (1%). The principal complications of pertussis are: apnea, secondary infections (such as otitis media and pneumonia), and physical sequelae of forceful coughing. Coughing transiently increases the intrathoracic and intra-abdominal pressure resulting in conjunctival hemorrhages, petechiae on the upper body, epistaxis, hemorrhage in the central nervous system and retina, pneumothorax and subcutaneous emphysema, and umbilical and inguinal hernias. Page - 192 Reversible bronchiectasis or pseudobronchiectasis occurs commonly after pertussis. The bronchi may appear cylindrically dilated on bronchography, but usually resolved in about 4 months. Patients with significant respiratory infections should be hospitalized if they are less than 3 months of age, (other causes of pneumonia presenting during the first weeks of life include C. Other indications for hospitalizations include: severe coughing paroxysms, cyanosis, poor social support, or an infection in a high risk patient (prematurity, cardiac disease, chronic pulmonary disease, neuromuscular disorder, etc. Admission orders should include: Cardiorespiratory monitoring, continuous pulse oximetry, apnea monitor. Detailed cough records (cyanosis, tachycardia, bradycardia, presence of coughed up mucus plug; post-tussive exhaustion and/or unresponsiveness). Prn oxygen, stimulation, or suctioning (note: suctioning of nose, oropharynx, or trachea always precipitates coughing, occasionally causes bronchospasm or apnea, and should be done prn only). Medication order should include: erythromycin (estolate form preferred) 40-50 mg/kg/day div qid (max 2 g/day 24 hr) x 14 days. Nursing orders should include: Respiratory isolation for at least 5 days after start of erythromycin. Restricting visitation of coughing family members who might be spreading pertussis to others in the hospital (until they have taken erythromycin for 5 days). Management orders of household close contacts should include: Erythromycin, 40-50 mg/kg/day divided qid (max 2 g/day 24 hr) for 14 days to all household and close contacts, i. Hospital discharge criteria should include clinical improvement plus: no intervention required during coughing, adequate nutrition, absence of complications, and the parents are prepared for further home care. The vaccine currently used in the primary immunization series is a safer acellular vaccine composed of a suspension of inactivated B. It resulted in more frequent pain, swelling, erythema, and systemic reactions, such as fever, fretfulness, crying, drowsiness, and vomiting. Febrile seizures, albeit rare, occurred within 48 hr and were brief, generalized, self-limited, and occurred more commonly in those with a history of seizures. Collapse or shock-like state (hypotonic-hyporesponsive episode) was rare, uniquely associated with pertussis vaccine, and has no permanent neurologic sequelae. Very rarely, pertussis vaccine was associated with acute neurologic illness in children who were previously normal. Severe adverse events, such as death, encephalopathy, onset of a seizure disorder, developmental delay, or learning or behavioral problems, have occurred in individuals temporally associated with pertussis immunization or alleged to be causally associated. The concept of herd immunity is that if 99% of the population is immune, then the infection can never find enough susceptible hosts to sustain itself and the few susceptible individuals within the population are unlikely to be exposed to the infection. However, herd immunity does not apply to pertussis since pertussis immunity declines substantially with age. Although teens and adults with pertussis will manifest with only mild to moderate respiratory symptoms, they represent a large population of susceptible individuals who can sustain an epidemic, and thus expose unimmunized infants and children, who may have more severe infections and complications. Upon admission to the ward you repeat the physical exam and also note retinal hemorrhages, which are confirmed by an ophthalmologist who just happens to be around. The parents have returned to the neighbor island for the weekend to fulfill important obligations and have already made arrangements to return on Monday. Given the presence of retinal hemorrhages, do you make a referral to Child Protective Services? Diphtheria, tetanus, and pertussis: recommendations for vaccine use and other preventive measures. Pertussis Vaccination: Use of acellular pertussis vaccines among infants and young children. Efficacy and immunogenicity of acellular pertussis vaccine by manufacturer and patient age. Choices a and e are the closest to being correct, but technically, these answers are incorrect. Suctioning of nose, oropharynx, or trachea always precipitates coughing, occasionally causes bronchospasm or apnea, and should be done prn only.