By: Edward T. F. Wei PhD
Over the following few days she had severe abdominal pain extreme diabetes in dogs buy discount losartan 25 mg online, a numb foot managing diabetes type 1 with diet 25 mg losartan free shipping, diarrhoea and an ongoing need for analgesia including opiates diabetes insipidus quality of life order 50mg losartan with mastercard. Staf were aware of her pain but interpreted it as normal post caesarean discomfort and she was not seen by a consultant diabetes type 2 early warning signs purchase generic losartan line. Two days later diabetes insipidus urine output cheap 50mg losartan mastercard, she was seen by the community midwife, her pain was worse, her abdomen was bruised and her foot numb. She was taken to labour ward, where she was in extremis with rectal bleeding, a grossly distended and bruised abdomen, hypotension and acidosis. She was taken straight to theatre for emergency surgery but died from complications of her extensive aortic dissection. This womans aortic dissection is likely to have occurred when she became hypertensive in the postpartum period, and was the cause of her severe postpartum pain. Her symptoms were typical of a descending aortic dissection, but not of the more common ascending aortic dissec tion, with severe pain, neurological features and symptoms of an ischaemic bowel. Escalation for senior review did not take place during her postnatal hospital care despite unexpected and unexplained severe symptoms. These enquiries have emphasised repeatedly the importance of senior review, and recognition that severe pain requiring opiates is a red fag. Given the increasing complexity of the maternity population, revision of this guidance is warranted to ensure that consultant review is appropriately triggered. N Repeated presentation with pain and/or pain requiring opiates should be considered a red fag and warrant a thorough assessment of the woman to establish the cause. She was an asylum seeker and engaged with care sporadically due to childcare issues. She had proteinuria noted on several occasions in the second trimester and received a single dose of methyldopa. Out of hospital resuscitation was stopped until it was realised she was pregnant, when it was recommenced. On arrival in the emergency department no scalpel was available, there was disagreement over the need for a perimortem caesarean section, and obstetric staf were delayed. Coronary atheroma and evidence of hypertensive heart disease were evident at postmortem. This woman had multiple problems, including multiple medical pathologies, social issues and sole responsibility for child care. The reasons for her non attendance and discharge against medical advice were never explored and the impact of her social situation was therefore not considered. Ensuring obstetric staf were in the Emergency Department when she arrived would have helped. All local maternity systems should ensure that there are defned pathways of referral for women with multiple and complex problems, both medical and social. The majority of women who died from cardiac conditions had multiple pathologies, and there should be a role for providing integrated advice on their care within new maternal medicine networks in England (Department of Health 2017) and similar services in the devolved nations. The new maternal medicine networks being developed in England and similar structures in the devolved nations should defne pathways of referral for women with multiple and complex problems. N Charging overseas visitors There was a suggestion that this woman and two others whose deaths are considered in this chapter may have been reluctant to access care because of concerns over the costs of care and the impact of their immigration status. Although no woman will be refused emergency treatment, this may not be commonly known. The importance of maternity care is recognised and is the only service explicitly classed as being immediately necessary in the regulations, meaning it cannot be withheld even if a woman has no means to pay. However, women may believe they will be asked to pay in advance for planned treatment and this may act as a disincentive to seeking care. Aortic dissection Most aortic dissections in women of reproductive age occur in and around pregnancy, thus awareness of the spec trum of clinical presentations and a low threshold for considering the diagnosis is important. Dissection occurs most often in the last trimester of pregnancy (50%) or the early post-partum period (33%) (Regitz-Zagrosek et al. Recognition of risk As noted above in the section relating to family history, with the currently evolving state of knowledge, ruling out known genetic mutations does not rule out an inherited aortopathy. Recognition of the risk of dissection will allow the signifcance of symptoms to be recognised. She had received tertiary care at a diferent hospital, but as her aortic root was not dilated she was not thought to be at risk of aortic dissection. Shortly after arrival in the emergency department she had a cardiac arrest due to an aortic dissection from which she could not be resuscitated. However, as with other women discussed in this chapter, there is no mention of a discussion about adequate contraception. Importantly, this womans death illustrates that aortic dissection can occur without aortic dilation in individuals with an underlying aortopathy. Consideration of the diagnosis Aortic dissection classically presents with severe sudden onset pain in the chest, back, neck or abdomen. However, a dissection extending into the abdominal aorta or head and neck vessels may cause additional symptoms and signs. Depending on the organs afected by the dissection, there may be neurological symptoms, haematuria or rectal bleeding. The combination of severe sudden onset pain and neurological symptoms should always raise the possibility of dissection. Underdiagnosis of aortic dissection is an important issue in the wider population and the subject of the current “Think Aorta campaign to increase identifcation and early diagnosis. A postnatal woman with known poorly controlled hypertension presented to the emergency department with sudden onset severe central chest pain and collapse. The following day she was found unresponsive at home and despite all attempts to resuscitate her she died from an aortic dissection and asso ciated cardiac tamponade. The assessment of this woman when she attended the emergency department was very thorough, but aortic dissec tion could have been higher in the diferential diagnosis given her symptoms. A specifc indication on the request to radiology that aortic dissection is a likely diferential diagnosis will lead to diferent consideration of which imaging is most appropriate in pregnant or postpartum women with chest pain. On both occasions she was investigated for presumed pulmonary embolism and discharged when investigations were negative. She collapsed at home a few days after her caesarean birth at which time the ischaemic heart disease from which she died was diagnosed. This woman had several risk factors for ischaemic heart disease and a strong family history, but no-one recognised their relevance. Women with established coronary artery disease are known to be at increased risk of adverse events during pregnancy (Regitz-Zagrosek et al. Echocardiography is recommended in any pregnant patient with unexplained or new cardiovascular signs or symptoms. She was discussed with a locum emergency medicine consultant and sent home with a diagnosis of refux oesophagitis. Postmortem revealed acute myocardial infarction and a single vessel coronary artery thrombosis. This woman clearly had an acute coronary syndrome she had classical symptoms of angina and a raised troponin. There were at least four opportunities to make a diagnosis and provide life-saving treatment. The message repeated in previous maternal mortality reports did not reach the medical staf who cared for this woman: • Severe chest pain needs a positive diagnosis • Women of child-bearing age can have coronary disease • Chest pain at rest radiating to the jaw and left arm, associated with sweating and nausea represents an acute coronary syndrome (Box 3. During her ongoing haemorrhage she developed symptoms of acute myocardial infarction. She was treated with carboprost and transferred to theatre for management of her haemorrhage. Postmortem revealed atherosclerotic coronary arteries with no evidence of thrombus. Once venous access was established, the team quickly and appropriately managed her severe haemorrhage. However, carboprost is known to raise blood pressure and this may have worsened her cardiac ischaemia. Although this woman was not known to have cardiac disease, she had several risk factors for premature coronary disease, and in this instance, given her chest pain at the time, there should have been careful consideration before administering carboprost. She was found to be in ventricular fbrillation and paramedics therefore attempted resuscitation and transferred her to the emergency department. Postmortem showed triple vessel coronary atherosclerosis with a single thrombosed vessel. Following resuscitation from an arrest with a likely cardiac cause, coronary angiography ± percutaneous coronary intervention is the appropriate initial diagnostic investigation. However, recent analyses have started to identify some genetic associations which may help illuminate the pathogenesis (Adlam et al. In the absence of means of prevention or prediction, the mainstay of treatment remains rapid recognition and early intervention. A postpartum woman in her mid 30s collapsed at home after experiencing chest pain and breathlessness the day beforehand. She had a cardiac arrest after their arrival and was resusci tated and transported to hospital within 30 minutes. She had good immediate care in hospital with an early cardiology review, bedside echocardiography and coronary angiography which revealed a spontaneous coronary artery dissection. Postmortem examination suggested two areas of myocardial infarction possibly consistent with her history of previous chest pain. Myocardial disease Cardiomyopathies are diseases of the heart muscle; the heart may be afected in isolation (primary) or the disease process may involve other organs and be part of a systemic disorder. Some primary cardiomyopathies which are genetically determined are included in the group of inherited cardiovascular conditions such as aortopathies and ion channel diseases. Others are acquired however, even non genetic forms of cardiomyopathy may be shaped by an individuals genetic profle and a family history of early onset cardiomyopathy is important. In a number of cases the symptoms and signs of heart failure were not appreciated. One woman, with multiple co-morbidities, died despite having been counselled against a further pregnancy. In addition, four women died from a dilated cardiomyopathy, two from arrhythmogenic right ventricular cardiomyopathy and one from Danon cardiomyopathy. A further three women had an unspecifed cardiomyopathy; the autopsy was not of sufcient quality to determine the type (see section 3. Four women died with left ventricular hypertrophy; in two of these women it was associated with morbid obesity. A further two women died from myocarditis, two dysrhythmias with structural heart disease, and one from post-heart transplant heart failure. She was initially admitted to a surgical ward and investigated for a gastrointestinal cause and then a small pulmonary embolus, but her severe left ventricular dysfunction was diagnosed quickly and treated appropriately.
Shifting dullness on percussion to the abdominal wall near surgical scars and a is more specific but less sensitive than flank dullness needle inserted close to a scar may enter the intestine diabetes medications renal failure generic 50mg losartan amex. Occasionally Analysis of the ascitic fluid is useful in the differential massive ovarian or hydatid cysts and pregnancy with diagnosis of ascites diabetes symptoms glucose in urine buy 25mg losartan overnight delivery. The gross appearance of the hydramnios can masquerade as ascites as they can fluid may be helpful in determining the pathologic also be associated with fluid thrill diabetes mellitus quadro clinico losartan 50 mg free shipping. In ascites due to portal hypertension or reported to detect as little as 120 ml of fluid clinically hypoalbuminaemia blood sugar effect on blood pressure generic losartan 50 mg overnight delivery, the fluid is clear and straw requires the patient to be in knee-elbow position coloured; turbid ascites may indicate infection diabetes type 1 symbol purchase losartan 50 mg amex. It provides immediate thrombosis, recent abdominal punctures or due to a information about the possible bacterial infection. Dark brown fluid may indicate the Samples with a predominance of neutrophils and an presence of bile. Lymphocytes predominate in suspected infection of ascitic fluid, suspected tuberculosis. Low Portal vein thrombosis Bowel obstruction or infarction protein ascites with total protein concentration of less than 2. A higher protein ascites with total Myxoedema protein concentration of more than 2. However, a total protein Culture of the ascitic fluid for bacteria should be concentration of greater than 2. The gradient secondary peritonitis due to gut perforation but is is calculated by substracting the ascitic fluid albumin only about 10 percent sensitive in detecting bacteria level from the serum level obtained on the same day. Low glucose can also be found in malignant corresponding difference in oncotic forces. Triglyceride levels are low in 84 Journal of Indian Academy of Clinical Medicine Vol. This procedure is rarely needed to detect presence of large number of degenerating peritoneal carcinomatosis because of the sensitivity of malignant or inflammatory cells. Rarely, fluid may be mucinous in character Umbilical hernia suggesting pseudomyxoma peritonei. Some patients may develop or may show an increase in the size of already existent umbilical hernia. Most Role of imaging hernias recur after surgical repair unless the ascites Radiologic studies are useful in detecting small amounts is controlled. Abdominal sonography may Hydrothorax detect as little as 100 ml of intraperitoneal fluid20. Pleural effusion, particularly on the right side can Although sonography is more cost-effective than develop in some patients with ascites. In patients with Bactericidal activity parallels the total protein carcinomatosis or inflammatory peritonitis, a contrast concentration in the fluid. Similar results with peritoneal patients with protein concentrations lower than 1 g/ abnormalities have recently been reported for magnetic dl during hospitalisation than in those with 22 concentration higher than 2 g/dl24. The most common features are fever fluoroscopy can demonstrate leakage of pancreatic juice and abdominal pain, but patients may present with from the pancreatic duct. Definitive diagnosis requires diagnose the intraperitoneal origin of the thoracic fluid. The most important finding Laparoscopy in the ascitic fluid is an elevated neutrophil count. A count of 250 cells/mm3 or more is considered With the availability of new imaging techniques, the diagnostic25. Most of the episodes are due to single need for laparoscopy in determining the cause of ascites has decreased. Secondary bacterial unclear, laparoscopy with direct visualization of the peritonitis should be suspected if the infection is peritoneum may be indicated. Cefotaxime, a third generation Ascites in cirrhosis generally occurs within 10 years cephalosporin, is the best studied antibiotic for treating of diagnosis in about 50 % of patients. A 5-7 day course of parenteral antibiotics seems may present with moderate ascites, tense ascites, to be sufficient. Aminoglycosides should be avoided refractory ascites, hyponatraemia, or with because of increased risk of nephrotoxicity in patients hepatorenal syndrome. Thus, strict bed rest is often Treatment of Ascites recommended because of improved renal clearance in supine position. Ascites due to causes other than chronic liver Sodium intake needs to be restricted to about 800 disease 1000 mg (2g NaCl) in order to induce a negative Treatment of non-cirrhotic ascites is to be directed at sodium balance and permit diuresis. Appropriate chemotherapy is favourable to respond to bed rest and salt restriction needed for infective causes. The management of include recent onset ascites, a reversible liver disease, chylous ascites will depend upon the underlying cause. In about 20% triglycerides substituted for the normal long chain of cirrhotics with ascites, urinary sodium triglycerides may help decrease the triglycerides concentrations are relatively high. Treatment of pancreatic restriction of sodium and bed rest alone may result ascites is controversial. Fluid restriction is not to conservative measures like salt restriction, diuretics necessary unless hyponatraemia is present. Somatostatin infusion may of patients, a negative sodium balance can only be help by reducing the pancreatic exocrine secretion29. For a patient with mild to moderate ascites, therapy the management of malignant ascites is an important can be undertaken as an outpatient and should be clinical problem when ascites causes severe gradual and incremental. Repeated therapeutic paracentesis is treatment is a loss of weight of not more than 1. If malignant cells are present in the ascitic kg/day if both ascites and edema are present and fluid and there are no intra-abdominal tumour not more than 0. Spironolactone, an aldosterone antagonist is with chemosensitive malignancies by intraperitoneal preferred as the initial diuretic. The recommended without malignant cells in the ascitic fluid, a starting daily dose is 50 to 100 mg/day and a peritoneovenous shunt may be of value in the control maximum of upto 400 mg/day may be given in one of resistant ascites1. Spironolactone may not provide 86 Journal of Indian Academy of Clinical Medicine Vol. The most important factor paracentesis circulatory dysfuction, particularly in determining the unresponsiveness to aldosterone patients in whom more than 5 litres of ascitic fluid is antagonists is the presence of renal failure. When these patients are discharged from of a loop diuretic (furosemide) to spironolactone the hospital, they should be put on salt restriction and potentiates the effect of both drugs and reduces the diuretics to prevent reaccumulation of the fluid. A useful therapeutic approach may be to add 40 mg of furosemide for Management of refractory ascites 100 mg of spironolactone. The maximum dose of In about 10% of patients, the ascites is refractory to diuretics recommended is a combination of treatment with first line measures mentioned above. If a patient ascites is now defined as the ascites that cannot be fails to respond to these regimens, the physician mobilized or early recurrence of which. These include hyponatraemia, refractory ascites have severe disturbances of systemic renal failure due to depletion of intravascular volume haemodynamics and renal function36. Other side-effects development of refractory ascites usually indicates related to the use of spironolactone in cirrhotics are advanced underlying disease. The therapeutic options decreased libido, impotence and gynaecomastia in for this group of patients are discussed below. Muscle Repeated large volume paracentesis at intervals cramps may often be present. This can be performed on an removed to relieve dyspnoea, decrease early satiety, outpatient basis. Ascites recirculation with removal, and prevent pressure related leakage from the site of concentration and reinfusion of peritoneal fluid has paracentesis. Technical problems haemodynamically beneficial in patients with tense and life threatening complications like infection and ascites, contrary to the popular belief. The procedure randomized controlled clinical trials have has been performed at some centres as the standard demonstrated that large volume paracentesis with 37 therapy in diuretic refractory ascites. One limb of the shunt lies in the removed) is considered to be the treatment of choice peritoneal cavity and the other in the superior vena in patients with tense ascites33. A valve at required to prevent reduction in effective intravascular the venous end prevents backflow of blood into the volume. Flow is maintained by the peritoneovenous synthetic gelatins which are effective but may be pressure gradient. Moreover, this procedure has an postoperative period or at any time during follow up. However, obstruction of the prosthesis is the haemobilia and biliary vascular fistula, liver most common complication and occurs in 40-60% haematoma, stent migration and intra-abdominal of patients during first year of follow up39. Surgical portosystemic shunts in which the portal vein is used as an outflow tract (side to side portacaval References and mesocaval shunt. Cirrhosis, Portal hypertension, hypertension and are effective in clearing ascites. Oxford However, because of high incidence of hepatic University Press, 1996: 2085-100. Evaluation and hepatic and portal veins, resulting in an intrahepatic management of chylous ascites. The procedure is most commonly of the physical examination in the diagnosis of suspected used for the treatment of recurrent oesophageal ascites. A simple traditional surgical shunts is a decrease in morbidity bedside manoeuvre to detect ascites. Various studies have assessed the effects paracentesis in patients with liver disease. The serum associated with marked suppression of antinatriuretic ascites albumin gradient is superior to the exudate-transudate 88 Journal of Indian Academy of Clinical Medicine Vol. Am treatment in decompensated cirrhosis and congestive heart J Med 1984; 77: 83-5. Gastroenterology Bedside inoculation of blood culture bottles with ascitic fluid 1987; 93: 234-41. J Clin Microbiol 1990; 28: trial comparing albumin, Dextran-70 and polygeline in 2811-2. Am J comparing daily paracentesis with intravenous albumin with Roentgenol 1995; 165: 16-8. Paracentesis with comparison of contrast-enhanced fast multiplanar spoiled intravenous infusion of albumin as compared with gradient-recalled and spin-echo imaging. Should and investigative findings in 145 patients with tuberculous portosystemic shunt be reconsidered in the treatment of peritonitis diagnosed by peritoneoscopy and biopsy over a intractable ascites Incidence and predictive portosystemic stent-shunt procedure for refractory ascites. N factors of first episode of spontaneous bacterial peritonitis Engl J Med 1995; 332: 1192-7. Transjugular polymorphonuclear cell count and serum to ascites albumin intrahepatic portal-systemic shunt in the treatment of gradient in the diagnosis of bacterial peritonitis.
Lone atrial brillation in nel variation on cardiac repolarization and atrial brillation risk diabetes medications side effects purchase 50 mg losartan with mastercard. Patterns of ventricular tachyarrhythmias asso lation with Brugada electrocardiographic pattern: prevalence diabetes insipidus glycosuria purchase generic losartan from india, management diabetes mellitus zinc buy 25mg losartan, and ciatedwith training diabetes diet create your healthy-eating plan purchase losartan toronto, deconditioning and retraining in elite athletes without cardio correlation with prognosis blood sugar pills buy discount losartan line. Sodium channel mutations and susceptibility to heart Alzand B, Willems R, Heidbuchel H. Heart Delise P, Blomstrom-Lundqvist C, Vanhees L, Ivarhoff P, Dorwarth U, 2004;90:1487–1488. Oral beta-blockersfor mild to moderatehypertension during cationforarrhythmiceventsinpatientswithasymptomaticpre-excitation:Asys pregnancy. 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Is the risk of atrial brillation higher in athletes than in the American College of Chest Physicians. Europace 2009;11: apy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th 1156–1159. Postoperative atrial brillation is rillation: a prospective study of 309,540 men and women. Atrial remodeling, Interventions for preventing post-operative atrial brillation in patients undergo autonomic tone, and lifetime training hours in nonelite athletes. Andersen K, Farahmand B, Ahlbom A, Held C, Ljunghall S, Michaelsson K, tion and subsequent outcomes in contemporary patients undergoing cardiac sur Sundstrom J. Interventions for prevention of post the incidence of atrial brillation after coronary artery bypass grafting surgery Timing and route of management of de novo atrial brillation after cardiac and thoracic surgery. Eur J amiodarone for prevention of postoperative atrial brillation after cardiac sur Cardiothorac Surg 2006;30:852–872. Postoperative atrial brillation signi cantly increases mortality, hospital re one versus beta-blocker as a prophylactic therapy against atrial brillation follow admission, and hospital costs. Statin therapy and atrial brillation: systematic postoperative atrial brillation as an independent predictor for worse early and review and updated meta-analysis of published randomized controlled trials. Curr late outcomes after isolated coronary artery bypass grafting (multicenter Austra Opin Cardiol 2013;28:7–18. Zheng Z, Jayaram R, Jiang L, Emberson J, Zhao Y, Li Q, Du J, Guarguagli S, Hill M, 954. Postoperative atrial brillation in pa Prophylactic magnesium does not prevent atrial brillation after cardiac surgery: tients undergoing aortocoronary bypass surgery carries an eightfold risk of future a meta-analysis. Mariscalco G, Klersy C, Zanobini M, BanachM, Ferrarese S, Borsani P, Cantore C, meta-analysis of randomized controlled trials. Postoperative atrial brillation and mortality after coron patients by preoperative supplementation of n-3 polyunsaturated fatty acids: an ary artery bypass surgery. N-3 polyunsaturated fatty acids to prevent atrial brillation: updated systematic review. Rate Control versus Rhythm Control for Atrial Fib Coll Cardiol 2013;62:1457–1465. Chirillo F, Comoglio C, Cugola D, Cumetti D, Dyrda O, Ferrua S, Finkelstein Y, 968. Anticoagulation in Flocco R, Gandino A, Hoit B, Innocente F, Maestroni S, Musumeci F, Oh J, adults with congenital heart disease: the who, the when and the how Management of late atrial tachyarrhythmia long after Fontan oper randomized clinical trial. Transesophageal echocardiographic detection of atrial Protective effects of steroids in cardiac surgery: a meta-analysis of randomized thrombi in patients with non brillation atrial tachyarrhythmias and congenital double-blind trials. Giamberti A, Chessa M, Abella R, Butera G, Negura D, Foresti S, Carminati M, selective antiarrhythmic agent and its place in current treatment of atrial brilla Cappato R, Frigiola A. Van De Bruaene A, Delcroix M, Pasquet A, De Backer J, Paelinck B, Morissens M, 439–442. Scaglione M, Caponi D, Ebrille E, Di Donna P, Di Clemente F, Battaglia A, Sledge I. Meta-analysis of ablation of atrial utter and supraventricular tachycar Raimondo C, Appendino M, Gaita F. Acute and long-term results of radiofrequency ablation complex congenital heart disease. Incidence and management of dysrhythmias after Fontan on the occurrence of atrial brillation. Surgical therapy of arrhythmias in single Wetzel U, Hilbert S, Kircher S, Eitel C, Piorkowski C. Huo Y, Schoenbauer R, Richter S, Rolf S, Sommer P, Arya A, Rastan A, Doll N, tients. Maze pro patient perceptions of atrial brillation and anticoagulation therapy: the West cedureforatrial brillationassociatedwithatrialseptaldefect. Ef cacy of the maze procedure for tions for anticoagulant therapy in patients with atrial brillation. Update on interventional electrophysiology intervention on patients knowledge of Atrial brillation and anticoagulant ther in congenital heart disease: evolving solutions for complex hearts. Warfarin knowledge in patients with atrial brillation: implica ablation of atrial utter: clinical course and predictors of atrial brillation occur tions for safety, ef cacy, and education strategies. Int J Cardiol 2013;168: the effect of atrial brillation on outcomes in patients undergoing carotid end 1422–1428. Philippart R, Brunet-Bernard A, Clementy N, Bourguignon T, Mirza A, Babuty D, forpeoplefacinghealthtreatmentorscreeningdecisions. Elwyn G, Frosch D, Thomson R, Joseph-Williams N, Lloyd A, Kinnersley P, Valley Atrial Fibrillation Project. Valvular heart disease among non-valvular atrial making: a model for clinical practice. Completely thoracoscopic bilateral pul search Forum on the Treatment and Prevention of Atrial Fibrillation, Washing monary vein isolation and left atrial appendage exclusion for atrial brillation. J Thorac Car Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated diovasc Surg 2010;139:1269–1274. A randomised controlled trial to in study protocol for a randomised controlled trial. Arrhythmic complications after electrical cardioversion of acute with pre-existing atrial brillation. Ef cacy and safety of ablation for patients with non Electrophysiol Rev 2003;7:359–365. Catheter ablation in patients with persistent atrial brilla salicylic acid for patients undergoing carotid endarterectomy: a randomised tion. Each meeting between a physician and a child is an oppor Serious neurologic syndromes include unexplained focal tunity to assess developmental and behavioral issues. Focal Lesions Rules of thumb are principles with broad applications that A focal lesion must be considered in a seizure disorder. The rules are Focal lesions are likely in hemiparesis, ataxia, and blurred or easily learned and easily applied. As in children with autism and attention deficit hyperactivity disorder, children with global the purpose of this article is to outline red flags and to developmental delay virtually never have focal lesions. Regression and Stagnation When there is regression or marked stagnation, delayed the Role of Parents in Assessing Development development is a concern (Figure 1. Most presentations of A thorough history is essential to understanding develop global developmental delay result from a previous injury or mental concerns. William Osler once said, “Listen to the patient; he is trying to Chronological Age (years) Normal tell you the diagnosis. Developmental screening using Illness/Trauma parental reports or other instruments can be more accurate than clinical judgments. Promptly refer a child who has an established diagnosis associated with developmental delay (such as Saltatory Loss Neurodegenerative Down syndrome or autism. There are comprehensive lists of organic and psycho-social risk factors, but among the most Chronological Age (years) worrisome are a very low birth weight, a clear case of asphyxia, and neonatal complications. If childrens abilities do not improve with time, those Red Flags in Development children might be regressing. It is important to recognize When assessing a childs development, it is essential to pay that developmental delay or regressing skills can be caused attention to serious neurologic syndromes or other by raised intracranial pressure secondary to a tumor, conditions that raise important red flags. It might include such presentations as a child losing the ability to walk or an unexplained change in mental status (such as occurs in a school-aged child with adrenoleukodystrophy who fails to respond to psychostimulants for attention problems. Absent reflexes or a positive Gowers sign can be signs of spinal muscular atrophy or Duchenne muscular dystrophy. Midline lumbosacral abnormalities, such as sacral dimples, might indicate occult spinal dysraphism; other spinal or orthopaedic abnormalities can suggest a neuromuscular cause of delay. Seizures Psychomotor regression is often a feature of severe epilepsies, such as Lennox-Gastaut syndrome or infantile fetal alcohol and Down syndrome. Infantile spasms are a variety of generalized, signs of a neurocutaneous disorder, such as hypo or myoclonic seizures marked by brief motor spasms of the head hyperpigmentation — should be noted. The worry is that there might be an the skin for cafe au lait macules or ash-leaf spots enhanced underlying neurologic disease, such as tuberous sclerosis, with a Woods lamp examination can help diagnose neuro cerebral dysgenesis, and hypoxic-ischemic encephalopathy. The fundi might show a cherry-red spot with hepatomegaly and alert clinicians to the Head Circumference presence of a lysosomal disorder, such as Tay-Sachs. Developmental delay occurs when Macrocephaly, delay and regression might suggest there is a “substantial delay in one developmental domain Canavan/Alexander, Krabbe or metachromatic leuko or more. Microcephaly with delay and regression might be equal to or greater than two standard deviations below a clue to Rett syndrome or infantile neuronal lipofuscinoses. Note that developmental quotients are reported as and whether it crosses percentiles. Any attempt to be more accurate — for example, to differentiate a 71 from a 70 — can only lead to error. Skin and Facial Features Other features on physical exam ought to give cause for Another rule of thumb is that delays in one developmental concern.
The driver of the vehicle experienced a possible medical emergency diabetes icd 9 generic losartan 50mg on line, and the pickup crashed into woods in the median metabolic disease symptoms in dogs 25 mg losartan amex. There were a total of nine frefghters riding in the crew carrier on an interstate highway diabetes insipidus symptoms urine discount losartan 25mg mastercard. For unknown reasons diabete walk purchase genuine losartan, the vehicle left the roadway treatment diabetes elderly cheap losartan 50 mg on-line, struck the median cable barriers, and rolled. The driver of the vehicle later told law enforcement ofcials that he was sleep deprived and had consumed illegal drugs in the days and hours before the crash. As it approached the responding engine, the empty trailer began to hydroplane, and the entire tractor trailer unit drifted into the opposing lane of trafc. The tractor trailer struck the engine apparatus, which went of of the roadway and rolled. He was transported to the hospital, but was pronounced dead shortly after his arrival. The driver of the tractor trailer was charged with driving too fast for conditions and failure to remain in the travel lane. As the apparatus entered a left-hand curve, the vehicle went of of the right side of the roadway. The frefghter attempted to steer the apparatus back onto the roadway, but the rear of the apparatus came around counter-clockwise, and the vehicle began to roll. All three frefghters on the apparatus were wearing their seat belts at the time of the crash, but the passenger compartment had been so compromised during the rollover that all three frefghters were fully ejected from the vehicle. The frefghter was a passenger in the tanker as it drove from a hotel to its assigned work site for the day. At approximately 0630 hours, as the apparatus entered a roundabout, the left-front tire of the vehicle struck a raised curb. The driver attempted to brake and gain control of the vehicle, but 24 Firefghter Fatalities in the United States in 2016 it rolled, coming to rest on its right side. The frefghter was restrained by a seat belt, but he received fatal injuries in the crash. As he drove to the fre station, he crossed the center line to pass another vehicle, lost control, hit the guardrail, came back across the driving lanes, struck the other guardrail, and rolled. The frefghter, who was intoxicated by a combination of drugs and alcohol, was killed in the collision. Firefghter fatalities in vehicle collisions (including aircraft) 40 35 30 28 25 27 20 19 18 15 16 10 11 9 9 5 5 5 0 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Year Setting an example In 2016, of the 16 vehicle collision deaths where the frefghters could have been using seat belts, 10 of them were wearing seat belts at the time of the crash, setting an example even in a tragic loss. While the status of seat belt use remains unknown in three cases, in only three other cases were the deceased frefghters not wearing seat belts (and all three were fully ejected from their vehicles. The number of frefghters whose lives were saved by wearing seat belts in 2016, like any year, remains unreported. Cause of Fatal Injury 25 Other In 2016, fve frefghters died from causes of fatal injuries not previously categorized. Firefghters were dispatched to the scene and transported the frefghter to a hospital where he later died. His death was caused by undiagnosed hypertrophic cardiomyopathy, a disease where the heart muscle becomes abnormally thick and pumping blood becomes difcult. Shortly after assisting with placing the unit back in service, the frefghter complained of not feeling well to other frefghters. The frefghter was discovered deceased in his bunk at 0714 hours the following day. He drove to the training site, attached hoselines to a fre hydrant, and joined other frefghters at the side of a portable water tank. Shortly after arriving at the water tank, the frefghter collapsed and bent forward toward the tank. The frefghter was transported to the hospital where he later died as the result of a ruptured aortic dissection. The crew had selected non-contact pass-and-catch football drills as a cardiovascular warm-up for that day. His death was caused by cardiac ischemia related to rhabdomyolysis (a breakdown of muscle tissue that releases a damaging protein into the blood. Once on-scene, the frefghter assisted with the rescue of civilians over ground ladders. He was then directed to remove equipment from the apparatus in preparation for a dive. The dive was called of due to the current and due to the fact that everyone was accounted for. Heart attacks by type of duty (2016) Returning 1 Training 2 On-scene non re 5 Other on-duty 6 On-scene re 7 After 19 0 2 4 6 8 10 12 14 16 18 20 Number of deaths Nature of Fatal Injury 27 28 Firefghter Fatalities in the United States in 2016 Firefghter Ages Figure 11 shows the percentage distribution of frefghter deaths by age (at the time of injury) and nature of the fatal injury. Table 11 provides a count of frefghter fatalities by age and the nature of the fatal injury. Younger frefghters were more likely to have died as a result of traumatic injuries, such as injuries from an apparatus accident or becoming caught or trapped during frefghting operations. Stress-related deaths are rare below the 31 to 35-years-of-age category and, when they occur, often include underlying medical conditions. He was shot and killed as he responded to an emergency medical incident in a residence. As he entered the residence and walked down a hallway inside of the home, the patient shot him multiple times. He remained alone at the station to perform maintenance duties while other company members attended the drill. At some point, the frefghter ascended a ladder inside the station for these maintenance duties. When fre department personnel returned from the drill, they found the frefghter entangled in the fallen ladder. Fatalities by time of fatal injury (2016) 0100 0259 8 0300 0459 1 0500 0659 4 0700 0859 5 0900 1059 7 1100 1259 7 1300 1459 4 1500 1659 13 1700 1859 12 1900 2059 9 2100 2259 7 2300 0059 6 Unknown 6 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Number of deaths Firefghter Fatality Incidents by Month of Year Figure 13 illustrates the 2016 frefghter fatalities by month of year. Deaths by month of year (2016) January 5 February 5 March 7 April 4 May 4 June 8 July 15 August 9 September 11 October 5 November 8 December 8 0 2 4 6 8 10 12 14 16 18 20 Number of deaths Deaths by Time of Injury | Firefghter Fatality Incidents by Month of Year 31 32 Firefghter Fatalities in the United States in 2016 State and Region the distribution of frefghter deaths in 2016 by state is shown in Table 12. The highest number of firefighter deaths in 2016 (based on the location of the fire service organization) occurred in North Carolina with nine losses. Four states sufered six frefghter deaths: Michigan, New Jersey, New York, and Pennsylvania. Census Bureau defnes “urban as a place having a population of at least 2,500, or lying within a designated urban area. Fire department areas of responsibility do not always conform to the boundaries used by the Census Bureau. For example, fre departments organized by counties or special fre protection districts may have both urban and rural coverage areas. In such cases, where it may not be possible to characterize the entire coverage area of the fre department as rural or urban, frefghter deaths were listed as urban or rural based on the particular community or location in which the fatality occurred. These statistics are based on answers from the fre departments, and when no data from the departments were available, the data were based upon population and area served, as reported by the fre departments. Each organization uses a slightly diferent set of inclusion criteria that are based at least in part on the purposes of the information collection for each organization and data consistency. As a result of these difering inclusion criteria, statistics about frefghter fatalities may be provided by each organization that do not coincide with one another. This section will explain the inclusion criteria for each organization and provide information about these diferences. Detailed inclusion criteria for this report appear starting on page four of this report. The purpose of the study is to analyze trends in the types of illnesses and injuries resulting in deaths that occur while frefghters are on the job. This annual census of frefghter fatalities in its Appendix 41 current format dates back to 1977. Under this defnition, the study includes, besides uniformed members of local career and volunteer fre departments, those seasonal and full-time employees of state and federal agencies who have fre suppression responsibilities as part of their job description, prison inmates serving on frefghting crews, military personnel performing assigned fre suppression activities, civilian frefghters working at military installations, and members of industrial fre brigades. Impressed civilians would also be included if called on by the officer in charge of the incident to carry out specific duties. The term on duty refers to being at the scene of an alarm, whether a fire or nonfire incident; being en-route while responding to or returning from an alarm; performing other assigned duties, such as training, maintenance, public education, inspection, investigations, court testimony and fundraising; and being on call, under orders or on stand-by duty other than at home or at the individuals place of business. Fatalities that occur at a frefghters home may be counted if the actions of the frefghter at the time of injury involved frefghting or rescue. On-duty fatalities include any injury sustained in the line of duty that proves fatal, any illness incurred as a result of actions while on duty that proves fatal, and fatal mishaps involving nonemergency occupational hazards that occur while on duty. The types of injuries included in the frst category are mainly those that occur at an incident scene, in training, or in accidents while responding to or returning from alarms. Illnesses (including heart attacks) are included when the exposure or onset of symptoms are tied to a specifc incident of on-duty activity. Those symptoms must have been in evidence while the victim was on duty for the fatality to be included in the study. Fatal injuries and illnesses are included even in cases where death is considerably delayed. When the onset of the condition and the death occur in diferent years, the incident is counted in the year of the conditions onset. Medical documentation specifcally tying the death to the specifc injury is required for inclusion of these cases in the study. The study also does not include suicides as on-duty fatalities even when the suicide occurs on fre department property. In practice, there is no mechanism for identifying on-duty fatalities that are due to illnesses that develop over long periods of time. This creates an incomplete picture when comparing occupational illnesses to other factors as causes of frefghter deaths. This is recognized as a gap the size of which cannot be identifed at this time because of the limitations in tracking the exposure of frefghters to toxic environments and substances, and the potential long-term efects of such exposures. National Fallen Firefghters Foundation In 1997, fre service leaders formulated new criteria to determine eligibility for inclusion on the National Fallen Firefghter Memorial. The National Fallen Firefghters Memorial was built in 1981 in Emmitsburg, Maryland. The names listed there begin with those frefghters who died in the line-of-duty that year. Since 1992, the tax-exempt, nonprofit foundation has developed and expanded programs to honor our fallen fire heroes and assist their families and co-workers by providing them with resources to rebuild their lives. Since 1997, the Foundation has managed the National Memorial Service held each October to honor the frefghters who died in the line-of-duty the previous year. As of this writing, the Foundation will be honoring 95 frefghters who died in the line-of duty at the October 2017 Memorial Weekend.
A clearing house for diagnostic testing: the solution to ensure access to and use of patented genetic inventions The Potential Effect of Patents and Licensing Practices on Clinical Whole-Genome Sequencing As noted in the introduction to this section latenter diabetes definition buy losartan 50 mg visa, affordable clinical whole-genome sequencing is on the horizon diabetic diet 50 carbs buy losartan us. Once it is developed diabetes mellitus gestational order losartan 25mg with amex, clinicians hope to use a patients genomic information to guide near-term preventive strategies and treatment decisions diabetes type 1 psychological effects purchase losartan 25mg online. Given the promise of affordable whole genome sequencing diabetes medicine online shopping buy cheap losartan 50mg on line, the Committee explored whether a patent thicket could delay or prevent the development of this technology. In other words, would whole-genome sequencing infringe the majority of existing patents on isolated genes and association patent claims To answer that question, one must consider how whole-genome sequencing is accomplished. A variety of methods exist, but most rely on the massively parallel amplification and analysis of small sections of the genome and then assembly of the resulting sequences by sophisticated 175 information technology algorithms. The question then becomes whether such a process would infringe typical claims to isolated genes and association patent claims. At this time, there is uncertainty in the legal community concerning whether whole-genome sequencing would infringe patent claims on genes. Furthermore, differences in claim language among patent claims on genes may lead to differing infringement determinations. However, because of the distinct possibility that some patent claims on genes will be infringed by whole genome sequencing, these patents remain a concern as a potential barrier to the development of whole-genome sequencing. Although uncertainty exists as to whether patent claims on specific isolated genes would be infringed by whole-genome sequencing, one can be more confident that association patent claims would be infringed by whole-genome sequencing. These claims do not refer to particular molecular methods of detecting a gene or proteins presence. Thus, the claims could be interpreted as protecting multiple, unspecified methods, which would include whole-genome sequencing (as well as multiplex testing. The infringement of this claim, however, would further depend on using the presence of the gene to infer that the patient was at increased risk for late onset Alzheimer disease. If other association patent claims have a breadth similar to the above claims, association patent claims may create a patent thicket that challenges the development of 176 whole-genome sequencing. Finally, before whole-genome sequencing is performed routinely in the clinical diagnostic laboratory, it is likely that parallel sequencing of multiple genes will be routinely performed. This process relies on oligonucleotides that include partial or complete gene sequences that are typically protected by patent. Therefore, the use of these oligonucleotides may well infringe patent claims on probe molecules or genes, and these patents may create a thicket that prevents or delays the development of parallel sequencing of multiple genes. As in the case of multiplex tests, patent pools and clearinghouses are potential solutions to any thickets that arise in the area of whole-genome sequencing or parallel sequencing of multiple genes, but questions remain as to the viability of these potential solutions. Test Developers Have Limited Protection from Infringement Liability the challenges patents pose to innovations in testing are not limited to patent thickets and their associated problems. Patents can also constrain developers ability to conduct research needed to create new innovations. Existing exemptions from liability for patent infringement provide only limited protection to those who wish to use patent-protected isolated gene molecules or associations during research and experimentation to develop improved genetic tests. First, the common law experimental use exemption most likely would not protect test developers from liability for using patent-protected isolated gene molecules or associations in the course of developing a new test. The narrow exemption is limited to “actions performed for amusement, to satisfy idle curiosity, or for 177 strictly philosophical inquiry. So, these patents do not appear to pose as substantial a barrier to clinical access to whole-genome sequencing. That is, a laboratory that was not licensed rights to a particular patented platform could rely on another platform or develop its own platform for whole-genome sequencing. Indeed, several competing proprietary whole-genome sequencing platforms already exist. Duke University, the Federal Circuit described Duke Universitys legitimate business as “educating and enlightening students and 180 faculty participating in. An example is provided by a developer creating a multiplex test that includes a patented gene fragment. Experiments to develop and validate this test might involve testing patients or known samples to verify the tests performance. Such experiments would necessarily involve the use of the patent-protected gene fragment. Validation of the test by testing patients would also likely infringe any patent claims to testing patients and associating the designated gene with a phenotype. In the case of an academic medical center, such uses of the patented gene fragments and associations would be arguably commercial in nature because any test that was ultimately developed from these experiments would be offered as a laboratory-developed test. Even if this use somehow was not commercial, one could argue that the use of the gene fragment or association to develop a genetic test would not be eligible for the exemption because it would relate to the legitimate business of an academic medical center in developing clinically useful diagnostics that improve patient care. In the case of companies using a patented gene fragment in the course of experiments to develop tests that involve those fragments, such experimental use would almost certainly be commercial in purpose and related to the companys business of developing biotechnology products or services; in that case, the company would not be entitled to the exemption. One jurist has observed that such limitations on research are at odds with the role of patents in disclosing knowledge: the purpose of a patent system is not only to provide a financial incentive to create new knowledge and bring it to public benefit through new products; it also serves to add to the body of published scientific/technologic knowledge. The requirement of disclosure of the details of patented inventions facilitates further knowledge and understanding of what was done by the patentee, and may lead to further technologic advance. The right to conduct research to achieve such knowledge need not, and should not, await expiration of the patent. Yet today the court disapproves and essentially eliminates the common law research exemption. This change of law is ill-suited to todays research-founded, technology-based 181 economy. Even if one were to argue that Madeys interpretation of experimental use was confined to research tools such as the invention used in Madey, genes claimed in some patent claims can serve as research tools in some contexts. The case did not involve the common law research exemption—instead, it was about the statutory research exemption, which is discussed in subsequent paragraphs of this report. This statutory exemption is found in the Hatch-Waxman Act and provides an exemption from patent infringement liability for using a patented invention for the purpose of 182 developing and submitting information under a Federal law regulating drugs. As part of the review process, the test developer would have to demonstrate the tests analytical validity, which could involve performing the kits 184 genetic test on patients. Therefore, any clinical testing done as research to develop a laboratory-developed test likely 187 would not fit within the Hatch-Waxman exemption. The majority of genetic tests are offered as laboratory-developed tests, rather than as testing 188 kits. In sum, it appears that test manufacturers are eager to develop—and clinicians are eager to use— multiplex tests, rather than single-gene tests, to carry out genetic testing. Patent claims on isolated genes and association patent claims, however, appear to have already created a thicket of intellectual property rights that may prevent innovators from creating these multiplex tests. Similar concerns arise when envisioning the clinical application of whole-genome sequencing. Such scenarios threaten to diminish the usefulness of these promising technologies and their application to patient care. The creation of a patent pool or clearinghouse is a possible, but uncertain, solution to the patent thicket facing multiplex tests and whole-genome sequencing. Such information would enable technology developers to more easily determine the necessary licenses for planned innovations. As multiplex testing and whole-genome sequencing become commonplace in medicine, challenges to innovators in obtaining access to licensing information may discourage the development of advanced tests and their application to medicine. Several public commenters were of the view that recent legal decisions have obviated any need for change; others suggested that the decisions did not alter what were viewed as existing threats to patient access. Congressional committee reports accompanying the Patent Act of 1952 indicate that Congress intended patentable statutory subject matter under § 101 to “include anything under the sun that 190 is made by man. Based on this legal principle, the genes found in nature—the genes within a humans cells, for example—cannot be patented. In that case, Judge Learned Hand held that adrenaline purified from a gland was patentable. In finding the invention patentable, Judge Hand reasoned that purified adrenaline differed “not in degree, but in kind from the adrenaline 189 the case was decided in March 2010 after the approval of this report. No major opinion apparently has addressed whether the exclusion of laws of nature from patent-eligibility is constitutionally mandated, although this may be the case, because patents on laws of nature would not serve to promote the progress of useful arts. The isolation and purification exception to the general unpatentability of products of nature. Oysters and oligonucelotides: concerns and proposals for patenting research tools. Purification and isolation here refer not to absolute purity, but to the general absence of other large molecules and biological substances. Supreme Court considered a different inquiry: whether a living thing that did not occur naturally was patentable. A case that was closely watched by the biotechnology community, Charkrabarty concerned the patentability of a bacterium that had 196 been genetically altered by introducing plasmids that enabled it to degrade oil. The Supreme Court held that the bacterium qualified as a patentable manufacture or composition of matter because it was “a new bacterium with markedly different characteristics from any found in 197 nature and one having the potential for significant utility. No case, however, has squarely considered the question of whether 199 isolated, purified nucleic acid molecules are patentable subject matter. Conley and Makowski argue that the focus of the patentability inquiry, as established in Parke-Davis and Charkrabarty, is not on purification per se, but on whether an invention derived from nature differs “in some substantial and material 194 Parke-Davis & Co. At least some cases before Parke-Davis that considered whether claimed inventions derived from nature were patentable found that they were not patentable—see, for example, American Wood-Paper Co. Even some cases after Parke-Davis found such inventions not to be patentable—see, for example, General Electric Co. Different perspectives on the evolution of “products of nature jurisprudence can be found in Gipstein, op. Back to the future: rethinking the product of nature doctrine as a barrier to biotechnology inventions (Part I. Journal of the Patent & Trademark Office Society 85:371-398; and L Andrews and J Paradise. Paper presented at the Conference on Living Properties: Making Knowledge and Controlling Ownership in the History of Biology. District Court, Southern District of New York, the plaintiffs argue that patents on isolated nucleic acid molecules and association patent claims violate “long established principles 206 that prohibit the patenting of laws of nature, products of nature, and abstract ideas. If the defendants prevail, the Committees recommendation will still be relevant because gene patents and associations will remain enforceable. But even if the plaintiffs prevail, the decision would not lead to the automatic 208 invalidation of all existing patents on genes and associations. Conley and Makowskis statement that the invention must have material differences over the product of nature is simply a way of rephrasing the Parke-Davis requirement that the invention differ in kind from the product of nature.
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