Accelerated idioventricular rhythm (AIVR) was first described by Thomas Lewis in 1910.1 AIVR is currently defined as an enhanced ectopic ventricular rhythm with at least 3 consecutive ventricular beats, which is faster than normal intrinsic ventricular escape rhythm (≤40 bpm), but slower than ventricular tachycardia (at least 100-120 bpm).1 Importantly, there is rate overlap between AIVR and some slow ventricular tachycardia. AIVR should not be diagnosed solely based on ventricular rate. Other characteristics of AIVR are helpful for its correct diagnosis (see Differentials).
AIVR is generally a transient rhythm, rarely causing hemodynamic instability and rarely requiring treatment. However, misdiagnosis of AIVR as slow ventricular tachycardia or complete heart block can lead to inappropriate therapies with potential complications. AIVR is often a clue to certain underlying conditions, like myocardial ischemia -reperfusion, digoxin toxicity, and cardiomyopathies.2,3,4
Pathophysiology
In most cases, the mechanism of AIVR appears to be related to the enhanced automaticity in His-Purkinje fibers and/or myocardium5 , sometimes accompanied with vagal excess and decreased sympathetic activity.6 Ischemia, reperfusion, hypoxia, drugs, and electrolyte abnormalities can all accelerate the phase 4 action potential depolarization rates in His-Purkinje fiber and myocardium, leading to faster spontaneous cell depolarization (enhanced automaticity).7 When the enhanced automaticity in His-Purkinje fiber or myocardium surpasses that of sinus node, AIVR manifests as the dominant rhythm of the heart. Sinus bradycardia may facilitate the appearance of AIVR.
Under certain conditions such as acute ischemia and digoxin toxicity, triggered activity has been suggested as the mechanism for AIVR.8
Most AIVRs originate from a single focus. Occasionally, in patients with acute myocardial ischemia and myocarditis, AIVR can originate from multiple foci.9,10 The ventricular rate of AIVR is generally between 40 to 100-120 bpm.
Usually, AIVR is hemodynamically well tolerated due to its slow ventricular rate. It is self-limited and resolves as sinus rate surpasses the rate of AIVR. Rarely, AIVR can degenerate into ventricular tachycardia or ventricular fibrillation. In patients with severe myocardial dysfunction, AIVR may lead to hemodynamic instability due to the loss of AV synchrony or relatively rapid ventricular rate.
AIVR in accute myocardial infarction
Clinically, AIVR has been best studied in patients with acute ST-elevation myocardial infarction (STEMI). In the thrombolysis era, AIVR was noted to be a marker of reperfusion.11 However, not all patients with reopened coronary artery have AIVR. In patients with acute myocardial infarction treated with primary percutaneous coronary intervention, the reported incidence of AIVR varied significantly, raging from 15-50%, depending on methods of monitoring.7,12
Recently, studies in patients with STEMI treated with primary percutaneous coronary intervention support that AIVR is a marker of occluded coronary artery reopening, but is not necessarily a marker for complete reperfusion. In fact, AIVR seems to be associated with more extensive myocardial damage and delayed microvascular reperfusion12 , although the mortality rates are similar in patients with and without AIVR.
Frequency
United States
The true prevalence of AIVR is unknown.
International
The true prevalence of AIVR is unknown.
Mortality/Morbidity
In general, AIVR does not significantly affect the patients’ mortality and morbidity.
In a very small retrospective observation study, AIVR was found to be associated with lower 7 days survival in postresuscitation patients.13
Race
No racial preponderance exists.
Sex
Men and women are equally affected.
Age
No age predilection exists.
Clinical
History
History is helpful for identifying the underlying etiology for AIVR. The presence of the following conditions supports a potential diagnosis of AIVR.
•Most patients with AIVR have chest pain or shortness of breath, symptoms related to myocardial ischemia. They often have recent history of myocardial reperfusion with drugs or coronary artery interventions.
•Some patients with AIVR have chest discomfort, shortness of breath, peripheral edema, cyanosis, clubbing, symptoms related to cardiomyopathy, myocarditis, and congenital heart diseases.
•Occasionally, patients with AIVR have history of using digoxin, some anesthetic agents, or illicit drugs such as cocaine.
•Rarely, AIVR can occur in people without apparent heart disease and no identifiable triggers.
Physical
There are no specific physical findings for AIVR. The following physical signs may be present.
•Slow (<55 bpm) or fast (>100 bpm) pulse rate.
•Variable heart sound intensity and cannon A waves related to atrioventricular dissociation.
•Some irregularity of heart rate/pulse rate due to competing sinus rhythm and AIVR.
•Rarely, hypotension related to either AV asynchrony or relatively rapid ventricular heart rate during AIVR.
Causes
The AIVR can occur in people with and without apparent heart diseases.14 The most common cause of AIVR is myocardial ischemia-reperfusion. Other causes include the following:
•Buerger disease15 •Congenital heart disease16 •Dilated cardimyopathy4 •Myocarditis10 •Drugs: Digoxin toxicity3 , cocaine toxicity17 , and various anesthesia agents18,19 •Electrolyte abnormality
•Postresuscitation13
Friday, March 25, 2011
Blood Test for Emphysema
Endothelial microparticles (EMPs) in plasma may be an early marker for emphysema, according to a study published online March 11 in the American Journal of Respiratory and Critical Care Medicine.
Alveoli enable gas exchange between air and blood through the alveolar epithelium, interstitial connective tissue, and capillary endothelium. The stress of chronic smoking can destroy alveoli, resulting in emphysema. Increasing evidence suggests that apoptosis in alveolar endothelial cells is a key element in the pathogenesis of lung damage.
EMPs are small vesicles that are released from activated or apoptotic endothelial cells, and plasma levels are elevated in vascular disorders. The researchers hypothesized that in smokers, EMP levels in plasma could be used as a marker for emphysema.
Cynthia Gordon, PhD, from the Department of Genetic Medicine, and Ronald C. Crystal, MD, senior author and chief, Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, New York City, and colleagues assessed lung health using pulmonary function tests, including total lung capacity (DLCO) and normal spirometry, as well as chest X-ray. Smoking status was determined by urine nicotine and cotinine. The researchers classified EMP levels (CD42b−CD31+ microparticles) as activated or apoptotic.
The study included an initial cohort of 92 healthy nonsmokers (defined by pulmonary function test), healthy smokers, and smokers with early signs of lung destruction (normal spirometry, low DLCO). The researchers then tested 2 prospective cohorts: One group was similar to the first, and another was HIV1-positive.
Compared with healthy nonsmokers, there was a slight increase in EMP levels in healthy smokers with normal spirometry and normal DLCO, as well as symptomatic smokers (P < 10−4 for both comparisons). The researchers found no differences between healthy smokers and symptomatic smokers (P > .4).
However, EMP levels were significantly higher in healthy smokers with normal spirometry but low DLCO (P < 10−4 compared with healthy nonsmokers; P < 10−3 compared with healthy smokers). EMP levels in healthy nonsmokers were between 0 and 500 EMP/μL. In 50% of healthy smokers, EMP levels were above the normal range seen in healthy nonsmokers. EMP levels were above the range of healthy smokers in 95% of healthy smokers with normal spirometry and low DLCO: 52% were distributed between 500 and 1250 EMP/μL, and 43% had levels higher than1250 EMP/μL.
Ratios of CD62+/CD31+ were reduced (P < 10−4), and CD42b−CD31+ annexin V+ EMPs were elevated (P < 10−4). These results suggest involvement of endothelial apoptosis.
Most elevated EMPs were positive for angiotensin converting enzyme, a sign that they might originate from pulmonary capillaries. The data from the initial cohort were confirmed in both prospective cohorts.
The results suggest that EMP levels could be a useful means of screening for early stages of emphysema without resorting to radiation exposure that is associated with chest high-resolution computed tomography.
"Interestingly, the smokers with the highest plasma EMP levels are healthy smokers with normal spirometry and isolated low DLCO. This suggests that the vascular-based contributions to the pathogenesis of emphysema may contribute to the early development of emphysema, and may identify a point in time where intervention with smoking cessation therapy may prevent the irreversible lung destruction associated with the development of (chronic obstructive pulmonary disease)," the authors write.
The study was supported in part by grant funding from the National Institutes of Health. The authors have disclosed no relevant financial relationships.
Alveoli enable gas exchange between air and blood through the alveolar epithelium, interstitial connective tissue, and capillary endothelium. The stress of chronic smoking can destroy alveoli, resulting in emphysema. Increasing evidence suggests that apoptosis in alveolar endothelial cells is a key element in the pathogenesis of lung damage.
EMPs are small vesicles that are released from activated or apoptotic endothelial cells, and plasma levels are elevated in vascular disorders. The researchers hypothesized that in smokers, EMP levels in plasma could be used as a marker for emphysema.
Cynthia Gordon, PhD, from the Department of Genetic Medicine, and Ronald C. Crystal, MD, senior author and chief, Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, New York City, and colleagues assessed lung health using pulmonary function tests, including total lung capacity (DLCO) and normal spirometry, as well as chest X-ray. Smoking status was determined by urine nicotine and cotinine. The researchers classified EMP levels (CD42b−CD31+ microparticles) as activated or apoptotic.
The study included an initial cohort of 92 healthy nonsmokers (defined by pulmonary function test), healthy smokers, and smokers with early signs of lung destruction (normal spirometry, low DLCO). The researchers then tested 2 prospective cohorts: One group was similar to the first, and another was HIV1-positive.
Compared with healthy nonsmokers, there was a slight increase in EMP levels in healthy smokers with normal spirometry and normal DLCO, as well as symptomatic smokers (P < 10−4 for both comparisons). The researchers found no differences between healthy smokers and symptomatic smokers (P > .4).
However, EMP levels were significantly higher in healthy smokers with normal spirometry but low DLCO (P < 10−4 compared with healthy nonsmokers; P < 10−3 compared with healthy smokers). EMP levels in healthy nonsmokers were between 0 and 500 EMP/μL. In 50% of healthy smokers, EMP levels were above the normal range seen in healthy nonsmokers. EMP levels were above the range of healthy smokers in 95% of healthy smokers with normal spirometry and low DLCO: 52% were distributed between 500 and 1250 EMP/μL, and 43% had levels higher than1250 EMP/μL.
Ratios of CD62+/CD31+ were reduced (P < 10−4), and CD42b−CD31+ annexin V+ EMPs were elevated (P < 10−4). These results suggest involvement of endothelial apoptosis.
Most elevated EMPs were positive for angiotensin converting enzyme, a sign that they might originate from pulmonary capillaries. The data from the initial cohort were confirmed in both prospective cohorts.
The results suggest that EMP levels could be a useful means of screening for early stages of emphysema without resorting to radiation exposure that is associated with chest high-resolution computed tomography.
"Interestingly, the smokers with the highest plasma EMP levels are healthy smokers with normal spirometry and isolated low DLCO. This suggests that the vascular-based contributions to the pathogenesis of emphysema may contribute to the early development of emphysema, and may identify a point in time where intervention with smoking cessation therapy may prevent the irreversible lung destruction associated with the development of (chronic obstructive pulmonary disease)," the authors write.
The study was supported in part by grant funding from the National Institutes of Health. The authors have disclosed no relevant financial relationships.
Monday, March 14, 2011
Fall of statues on Tank Bund
Statues on tank bund fell. Statues are of the ones, who were stalwarts, who were never petty or parochial nor had any viciousness of Seemandhra leadership. Never should we compare them with the crony capitalists and the Andhra ruling midgets. This destruction, in a way, slights their contribution; but these statues are caught up in the cross-fire between the indolent and intransigent state/central governments and the relentless Telanganites. These are destroyed out of anger against Andhra rulers rather than anger on them per se.
But I must also say that there is another side to it as well; more about flesh, blood and life of struggling Telangana people. A civilised world should be more worried about people than the statues.
The Andhra media is shouting hoarse describing the agitators as lumpen disturbing the order. It is similar to white right winger press crying hoarse when blacks revolted in America and South Africa.
Setting the illegality of the act aside and wishing that it would not happen again, let us look at the ones who installed them on the bund. By reading installers and their minds, we get the social construct and the deeper meaning behind the rise and fall of the statues. Let us look at it as social scientists and not as advocates of one cause or the other.
There is a social agenda in erecting them in Hyderabad. When British came to India they brought English language first. When laissez-faire (free market) enters in the name of reforms, coca cola heralds it. Europeans (Spanish) took their religious icons to subjugate after conquering Latin America.
Similarly, for cultural enslavement, Andhra elite have brought in these icons as cultural weaponry to dismiss our very own identity.
Tank bund was built by Hussain, a Sufi engineer 200 hundred years ago. NTR/TDP changed the very character of the region by wholesale importation of the Andhra culture, cultural and historical icons. Historically important Husain’s tank bund was defaced. This ‘period’ structure was distorted. It is an assault on native Hyderabadi and Telangana culture, as Shilparamam is an onslaught on NUMAISH and telangana cultural ethos. Victorious roman conquerors and British conquerors put their statues on the land of the vanquished in a similar way. Jagan wants to seal his grip on the people by YSR statues, like land mines are planted so that no one moves away from him. It is not about Krishna deveraya in that statue. He was great by himself. But there is also an Andhra social and political order in it. There is thought control in it. There is suzerainty and Andhra cultural hegemony in it. NTR’s carving out of the above statue in his own image tells it all, that it is symbolic of the Andhra ruling elite power over the natives.
By submerging it in Husain-sagar waters Telanganites have symbolically washed themselves of this. It is declaring their cultural independence and with their collective unconscious they have declared that they are a separate state and culture and they have nothing in common culturally with Andhra.
If one is non judgemental, in socio psychological perspective, this is the only explanation. Commoners of Andhra should understand the dynamics of statue installations and see the things through.
August Comte, father of sociology, says that society is an organism by itself and not sum total of individuals. On the day of million march the primal force of Telangana was expressed. It would be a blessing, if the social scientists of India study this phenomenon to understand the nation and guide in its policy and planning, instead of leaving the nation in the hands of blinkered bureaucrats and petty professional self seeking politicians.
PS: For better understanding of statues read Carl Jung’s books on symbolism, Books on semiotics and symbolism and also a classic Book fore worded by jean paul satre “ The colonizer and the colonized” written by Albert Memmi
Thursday, March 3, 2011
INR -- INTERNATIONAL NORMALIZED RATIO
The current method for monitoring vitamin K antagonist (AVK) anticoagulant therapy is the international normalized ratio (INR) that provides consistency and standardization for the prothrombin time (PT) assay value. Even after the standardization of the INR, inaccuracies of this value have still been reported. To make the INR even more accurate, better local assessments of INR parameters are becoming available. These new methods use plasmas with certified INR values to locally verify and, if necessary, recalculate the international sensitivity index (ISI) for the local laboratory's reagent and instrument system. This CE Update will discuss the concepts of local verification and calibration to better define the manufacturer's assigned ISI value, thus reporting more accurate INR results.
Introduction
Our understanding of the basic science and clinical issues surrounding hemostasis has skyrocketed within the last 10 to 15 years. These advances have: 1) established better treatment for patients at risk for hemorrhage or thrombosis; 2) identified new hereditary coagulation disorders; and 3) provided mechanism(s) for clinical hemostatic diseases. With this in mind, clinicians have begun to put more demand on the coagulation laboratory. The laboratory has had to keep pace by developing new coagulation tests and better standardizing those tests already in use. The cornerstones of clinical coagulation testing are the prothrombin time and/or international normalized ratio (PT/INR) and the activated partial thromboplastin time (aPTT) for identifying and monitoring clinical coagulation disorders and therapeutics. Manufacturers have varied the sensitivities of these reagents to more easily assess this variety of clinical conditions. It now has become important for each laboratory to evaluate the commercial reagents to determine the most appropriate one for their clinical needs. The criteria for how reagents should be evaluated include: sensitivity for intended use, compatibility with instrumentation, number of assays performed each day, and cost.
In this CE Update, we discuss: 1) how to determine the INR; 2) how to locally verify and calibrate the PT reagent for more accurate INR values; and 3) the clinical use of the INR for monitoring anti-vitamin K anticoagulant therapy.
Oral Anticoagulant Therapy Monitoring Using the PT/INR
Anticoagulant therapy is used to treat and/or prevent both arterial and venous thrombosis.[1] Currently in the United States, IV anticoagulants (heparin and direct thrombin inhibitors [DTI]) are administered to inhibit further clot formation. The oral drug Coumadin (or warfarin) is given for long-term prevention of new thrombus formation; however, it is an indirect acting drug requiring 3 to 5 days to reach therapeutic effectiveness.[1] Warfarin derivatives are the standard therapy worldwide.[3] Annually, there are more than 21 million prescriptions written in the United States.[3] Warfarin derivatives (generally known as vitamin K antagonists [AVK]) act by inhibiting the vitamin K-associated post-translational modifications of the vitamin K-dependent clotting factors.[1] Unfortunately, warfarin has a very narrow therapeutic window and dosing responses vary between individuals of up to 10-fold and 2–3 fold within an individual caused by changes in medications, diet, or health status.[4] Warfarin is the second most common mismanaged therapeutic drug, requiring more than 40,000 emergency room visits per year and about $40 million to $60 million in additional medical costs per year.[4] The therapeutic window for oral anticoagulant drugs is very narrow; therefore the accuracy for monitoring these drugs' INR is essential since inadequate dosing increases thrombotic risk and excessive doses significantly increase the bleeding risk.
Monitoring AVK anticoagulant therapy using the INR is in its final phases of a slow transition in the United States compared with most European countries routinely using the INR value. The INR is a mathematically transformed or calculated value converting the PT in seconds to a standard ratio value.[1,2] The INR theoretically eliminates the differences in sensitivity of various PT reagents. However, within individual coagulation laboratories, the INR may not eliminate all of the variables of the PT assay, requiring local adjustment to make the reagent's INR more accurate with a specific instrument within the local environment.
Sensitivity to AVK anticoagulant therapy using the INR is the most important consideration when choosing a PT reagent.[2] A single plasma sample from an anticoagulated patient may give clinically significant different PT clotting times when tested against a variety of PT reagents; theoretically the INR value should be the same. It is important to pick a reagent with clotting times based on a scientific rationale rather than one with clotting times "familiar" to your clinicians.
Concept of the INR
The differences in PT results are dependent upon the composition of the PT reagent.[2] The reagent is composed of thromboplastin (tissue factor and phospholipid), extracted from a variety of sources (human and rabbit are the most common). Historically, each laboratory extracted thromboplastin from the human brain, but as commercial reagents were made available the major tissue source became rabbit brain. This is still used in a number of commercial reagents today. Now manufacturers are again starting to make reagents using human thromboplastin (placenta and recombinant).[5] The therapeutic responsiveness of the PT reagent is different depending on the source and composition of the thromboplastin.[1]
When the PT assay was first used to monitor AVK therapy, most providers based their therapeutic decisions on PT values in the range of 1.5 to 2.5 times the control value. However, now with the production of different reagent sensitivities with new sources of thromboplastin, the 1.5 to 2.5 range is not an accurate reflection of therapeutic anticoagulation.
In 1983, the World Health Organization (WHO) adopted a method to establish consistency of the PT value for patients on AVK.[6] This mathematical expression of the PT value is termed INR.[2] The INR calculation is based on the international sensitivity index (ISI) value specific to each PT reagent[1] and is valid only for stable AVK anticoagulant therapy and only up to an INR of 4.5.[1,2] An ISI value is determined for each thromboplastin reagent by comparing the responsiveness of the PT reagent with a WHO international reference preparation (IRP).[6,7]
Theoretically, the INR of a patient receiving AVK therapy would be the same regardless of the reagent and instrument used or in which the laboratory the sample was tested.[1,2,6] The specific PT reagent ISI value is determined using a WHO standard protocol comparing both PT reagent and IRP values from 20 normal individuals and 60 stable AVK individuals.[6,7] The slope of the regression calculation (orthogonal) of the 2 values is the ISI value of the unknown reagent.[2,6] Variation in the assigned ISI calculated by the manufacturer can vary +5%. This type of error can contribute to clinically different INR results.[6]
The INR is calculated using the assigned ISI value and the mean normal PT (MNPT) value (Figure 1).[2] The MNPT is determined by the laboratory using 20 to 40 (40 being optimal) healthy individuals reflecting the laboratory's patient base.[2] The mean is calculated using the geometric mean rather than the arithmetic mean.[2,8] The geometric mean assumes a non-normally distributed set of values. Geometric mean calculation transforms the data to log values before determining the mean. The arithmetic mean assumes a normally distributed normal population. The use of the arithmetic mean instead of the geometric mean can lead to a clinically significant difference in the MNPT and INR value.
Accuracy of the Manufacturer-assigned ISI
The ISI value reported in the PT reagent package insert has been determined by the manufacturer using the WHO standard method.[6] However, there are potential sources of error associated with this assigned ISI value (Table 1).[2,9] When these errors are compounded, a significant difference in the reported INR value and the true INR value can be found. These types of errors must be reduced by each laboratory. A manufacturer usually reports 2 ISI values for any PT reagent.[9,10] The first is the "generic ISI" and is determined for instruments using the same end-point detection method but not a specific instrument. This ISI must be used when the reagent of 1 manufacturer is used on an instrument made by a second manufacturer. However, the accuracy of this ISI value for the reagent-instrument system may be of clinical concern. The second reported ISI value is specific to the PT reagent and instrument combination ("instrument-specific ISI"). In several studies, the accuracy of INR results was enhanced when instrument-specific ISI was used instead of the generic ISI.[10,11] The range of discrepancy between the manufacturer-derived ISI and the local validated ISI can vary between +15% and 30%, thus making clinically significant differences in the INR value. Therefore the ISI value should be verified, especially in laboratories using generic ISI values. If the local validated ISI value is significantly different from the reported ISI, then the ISI must be determined locally.
i Initially, the ISI is assigned by the manufacturer based on the WHO ISI IRP. The yellow-shaded area shows the validation of the ISI at the local laboratory level. Every new reagent lot must at least be verified by the local laboratory. For proper local verification, the locally determined ISI must agree within 15% to be acceptable. If greater than 15%, then the ISI must be locally calibrated and re-verified.
Initially, the ISI is assigned by the manufacturer based on the WHO ISI IRP. The yellow-shaded area shows the validation of the ISI at the local laboratory level. Every new reagent lot must at least be verified by the local laboratory. For proper local verification, the locally determined ISI must agree within 15% to be acceptable. If greater than 15%, then the ISI must be locally calibrated and re-verified.
The definition of verification is "the confirmation through the provision of objective evidence that the specified requirements have been fulfilled" (within a pre-established set of criteria).[2,9] Verification is usually a 1-time process completed to confirm test performance before the INR system is used for patient testing. If significant differences in the INR test system are present, then calibration is performed followed by repeating the verification process. Calibration is "a set of operations establishing, under specified conditions, the relationship between true quantitative values indicated by the measuring test system."[9] For the INR test system, if the verification is not different from the reported ISI value, then calibration does not need to be performed. If significant differences (>15%) are found between the ISI values, then calibration of the ISI is required, followed by re-verification to ensure INR accuracy.[9,10]
The local verification and calibration (if necessary) of the ISI is performed with FDA-approved kits that provide all of the certified plasmas, the procedure, and data calculations. This ISI verification can be performed by any technologist or supervisor in all laboratories performing patient PT/INR results. The procedure usually takes 3 days of performing PT/INR testing on the certified plasmas and about 20 to 30 minutes of calculations that can be performed either by the manufacturer of the kit or through the manufacturer's Web-based program. This local verification and calibration procedure should be included in all new reagent and/or instrument contracts, cost per test, and cost per reportable result contracts. International sensitivity index verification and calibration (if necessary) should be performed (as part of the contract) at installation of the instrument, when starting a new reagent, for lot changes, and after instrument repair or internal or external QC issues. The procedure itself is relatively straightforward and has safeguards built in to provide a more accurate local ISI with clinically correct INR values.
Verification of the ISI in the Local Laboratory
The laboratory should not accept the initial ISI value assigned by the manufacturer as the local laboratory's working parameters, and conditions may significantly affect the patient's calculated INR results. With this in mind, it becomes the laboratory's responsibility to verify the validity of the ISI (Table 2).[9]
Two basic methods for local verification of ISI are available.[9] The first is the impractical method of using the WHO standard protocol. It is not feasible since it requires fresh plasma samples, an IRP, and the ability to perform the labor-intensive tilt tube assays. The second, more practical method uses certified plasmas to determine the ISI. These plasmas are purchased from the manufacturer of the reagent system or from an independent vendor especially for the reagent system. The verification kit should be part of the validation process for new installations, new reagents, and changes in reagents lots (Table 2). The procedure for verification per the provided instructions must be followed. The verification kit should be FDA approved following the established guidelines of Clinical and Laboratory Standards Institute (CLSI).[2,9] In brief, the procedure requires a minimum of 3 certified plasmas in the range of 1.5 INR to 4.5 INR. These plasmas can be lyophilized or frozen. The certified plasmas are evaluated exactly as patient samples. The PT and INR values are determined for each plasma tested in duplicate once per day for 3 days. The INR values obtained are compared to the assigned INR of the certified plasma. If these values compare within 15%,[2,9] then the ISI has been verified, and the PT reagent can be used with the assigned ISI value. If the verification procedure fails (INR values >15%), then a local calibration must be performed (see below).[2,9] Table 3 and Table 4 show examples of a passing verification and a failing verification, respectively. In Table 3, the mean INR values are within 15% of the assigned value for all 3 plasmas, the ISI is verified, and the assigned ISI value is correct. In Table 4, the highest INR certified plasma failed verification (>15%), so the assigned ISI cannot be used, and local calibration must be performed to determine a local valid ISI.
Local System Calibration of the ISI for the Local Laboratory
If verification fails, then the laboratory must not report patient results until the correct ISI is determined.[9] The laboratory must establish that: 1) instrument(s) was(were) working properly; 2) reagents were reconstituted correctly; 3) MNPT was determined accurately (geometric mean); and 4) no clerical or mathematical errors were made. If these are correct, then proceed to local calibration of the ISI.
Local calibration can be accurately determined using 2 methods: 1) calculating a local ISI, or 2) generating a PT/INR calibration line on which PT values are read as the INR value.[9] Whichever method is used, the calibration kit must be FDA approved. The certified plasmas must be compatible for the reagents and instruments used in the laboratory.[9] As an example, if the laboratory is using recombinant human thromboplastin, the calibration kit should be certified for use with human thromboplastin. The local ISI calibration procedure is a modification of the WHO protocol.[8,9] The PT values for each of the certified plasmas are determined using the local PT reagent and instrument. The local PT values are plotted against the assigned PT values of the certified plasma and an orthogonal regression line is calculated. The ISI calibration is considered valid if the slope has a CV of <3%.[9] The resulting slope of the line is the correct local ISI.[8,9] The procedure is similar to the verification method. The certified plasmas must be run in duplicate for at least 3 days to account for variation due to random error.
The necessary number of certified plasmas depends on a variety of factors, such as the source of the plasma (immuno-depleted or treated individual), type of plasma (frozen or lyophilized), single donor or multiple donors, and the IRP used for the certification of the plasma.[9] The manufacturer of the calibration kit in consultation with and approval by the FDA has determined the minimum number of certified plasmas needed. Most manufacturers will help the local laboratory determine the ISI value through either the Internet or as a "send-in" service. The manufacturer must provide detailed documentation of these ISI determination calculations for accreditation documentation. Of important note, after local calibration, the ISI must again be re-validated to confirm that the calibration and changed ISI are truly correct.
The second method to determine the local ISI is the direct INR calibration line, which is independent of the ISI value and the MNPT.[9] A disadvantage of this method is that many laboratory information systems and/or instrument systems are not programmed for calculating the INR by this method. Using this protocol, the PT values of certified plasmas are determined using the laboratory's system, also testing for 3 days in duplicate. The PT values determined locally are plotted on the y axis against the assigned certified plasma INR values (x axis). Using orthogonal regression, the best fit line is plotted. For a valid calibration curve, the r2 value of the regression line must be >0.95. The patient's INR is mathematically or graphically determined from this calibration line. Significant changes in the reagent-instrument system, such as lot changes, instrumentation repair, QC validity changes, and proficiency testing problems will all require establishing the INR calibration line and recertification
The INR is an important clinical tool for monitoring AVK therapy. The introduction of the INR has added several orders of magnitude of accuracy to anticoagulant monitoring. Still, more accuracy is needed to further reduce clinical problems associated with anticoagulation. To this end, the development of local reagent accuracy through the use of local ISI verification and ISI calibration adds even greater confidence to the correct reporting of INR values. The methods for ISI verification and the local ISI calibrations are just beginning to be used in the United States. The College of American Pathologists (CAP) Laboratory Accreditation program checklist (HEM.23220) requires documentation that the ISI is validated. The local ISI verification and calibration method fulfills that requirement. The methods may appear complex and the mathematics difficult, but kit manufacturers should assist with these calculations. Local determination of the ISI will significantly increase clinical confidence in oral anticoagulant monitoring.
Introduction
Our understanding of the basic science and clinical issues surrounding hemostasis has skyrocketed within the last 10 to 15 years. These advances have: 1) established better treatment for patients at risk for hemorrhage or thrombosis; 2) identified new hereditary coagulation disorders; and 3) provided mechanism(s) for clinical hemostatic diseases. With this in mind, clinicians have begun to put more demand on the coagulation laboratory. The laboratory has had to keep pace by developing new coagulation tests and better standardizing those tests already in use. The cornerstones of clinical coagulation testing are the prothrombin time and/or international normalized ratio (PT/INR) and the activated partial thromboplastin time (aPTT) for identifying and monitoring clinical coagulation disorders and therapeutics. Manufacturers have varied the sensitivities of these reagents to more easily assess this variety of clinical conditions. It now has become important for each laboratory to evaluate the commercial reagents to determine the most appropriate one for their clinical needs. The criteria for how reagents should be evaluated include: sensitivity for intended use, compatibility with instrumentation, number of assays performed each day, and cost.
In this CE Update, we discuss: 1) how to determine the INR; 2) how to locally verify and calibrate the PT reagent for more accurate INR values; and 3) the clinical use of the INR for monitoring anti-vitamin K anticoagulant therapy.
Oral Anticoagulant Therapy Monitoring Using the PT/INR
Anticoagulant therapy is used to treat and/or prevent both arterial and venous thrombosis.[1] Currently in the United States, IV anticoagulants (heparin and direct thrombin inhibitors [DTI]) are administered to inhibit further clot formation. The oral drug Coumadin (or warfarin) is given for long-term prevention of new thrombus formation; however, it is an indirect acting drug requiring 3 to 5 days to reach therapeutic effectiveness.[1] Warfarin derivatives are the standard therapy worldwide.[3] Annually, there are more than 21 million prescriptions written in the United States.[3] Warfarin derivatives (generally known as vitamin K antagonists [AVK]) act by inhibiting the vitamin K-associated post-translational modifications of the vitamin K-dependent clotting factors.[1] Unfortunately, warfarin has a very narrow therapeutic window and dosing responses vary between individuals of up to 10-fold and 2–3 fold within an individual caused by changes in medications, diet, or health status.[4] Warfarin is the second most common mismanaged therapeutic drug, requiring more than 40,000 emergency room visits per year and about $40 million to $60 million in additional medical costs per year.[4] The therapeutic window for oral anticoagulant drugs is very narrow; therefore the accuracy for monitoring these drugs' INR is essential since inadequate dosing increases thrombotic risk and excessive doses significantly increase the bleeding risk.
Monitoring AVK anticoagulant therapy using the INR is in its final phases of a slow transition in the United States compared with most European countries routinely using the INR value. The INR is a mathematically transformed or calculated value converting the PT in seconds to a standard ratio value.[1,2] The INR theoretically eliminates the differences in sensitivity of various PT reagents. However, within individual coagulation laboratories, the INR may not eliminate all of the variables of the PT assay, requiring local adjustment to make the reagent's INR more accurate with a specific instrument within the local environment.
Sensitivity to AVK anticoagulant therapy using the INR is the most important consideration when choosing a PT reagent.[2] A single plasma sample from an anticoagulated patient may give clinically significant different PT clotting times when tested against a variety of PT reagents; theoretically the INR value should be the same. It is important to pick a reagent with clotting times based on a scientific rationale rather than one with clotting times "familiar" to your clinicians.
Concept of the INR
The differences in PT results are dependent upon the composition of the PT reagent.[2] The reagent is composed of thromboplastin (tissue factor and phospholipid), extracted from a variety of sources (human and rabbit are the most common). Historically, each laboratory extracted thromboplastin from the human brain, but as commercial reagents were made available the major tissue source became rabbit brain. This is still used in a number of commercial reagents today. Now manufacturers are again starting to make reagents using human thromboplastin (placenta and recombinant).[5] The therapeutic responsiveness of the PT reagent is different depending on the source and composition of the thromboplastin.[1]
When the PT assay was first used to monitor AVK therapy, most providers based their therapeutic decisions on PT values in the range of 1.5 to 2.5 times the control value. However, now with the production of different reagent sensitivities with new sources of thromboplastin, the 1.5 to 2.5 range is not an accurate reflection of therapeutic anticoagulation.
In 1983, the World Health Organization (WHO) adopted a method to establish consistency of the PT value for patients on AVK.[6] This mathematical expression of the PT value is termed INR.[2] The INR calculation is based on the international sensitivity index (ISI) value specific to each PT reagent[1] and is valid only for stable AVK anticoagulant therapy and only up to an INR of 4.5.[1,2] An ISI value is determined for each thromboplastin reagent by comparing the responsiveness of the PT reagent with a WHO international reference preparation (IRP).[6,7]
Theoretically, the INR of a patient receiving AVK therapy would be the same regardless of the reagent and instrument used or in which the laboratory the sample was tested.[1,2,6] The specific PT reagent ISI value is determined using a WHO standard protocol comparing both PT reagent and IRP values from 20 normal individuals and 60 stable AVK individuals.[6,7] The slope of the regression calculation (orthogonal) of the 2 values is the ISI value of the unknown reagent.[2,6] Variation in the assigned ISI calculated by the manufacturer can vary +5%. This type of error can contribute to clinically different INR results.[6]
The INR is calculated using the assigned ISI value and the mean normal PT (MNPT) value (Figure 1).[2] The MNPT is determined by the laboratory using 20 to 40 (40 being optimal) healthy individuals reflecting the laboratory's patient base.[2] The mean is calculated using the geometric mean rather than the arithmetic mean.[2,8] The geometric mean assumes a non-normally distributed set of values. Geometric mean calculation transforms the data to log values before determining the mean. The arithmetic mean assumes a normally distributed normal population. The use of the arithmetic mean instead of the geometric mean can lead to a clinically significant difference in the MNPT and INR value.
Accuracy of the Manufacturer-assigned ISI
The ISI value reported in the PT reagent package insert has been determined by the manufacturer using the WHO standard method.[6] However, there are potential sources of error associated with this assigned ISI value (Table 1).[2,9] When these errors are compounded, a significant difference in the reported INR value and the true INR value can be found. These types of errors must be reduced by each laboratory. A manufacturer usually reports 2 ISI values for any PT reagent.[9,10] The first is the "generic ISI" and is determined for instruments using the same end-point detection method but not a specific instrument. This ISI must be used when the reagent of 1 manufacturer is used on an instrument made by a second manufacturer. However, the accuracy of this ISI value for the reagent-instrument system may be of clinical concern. The second reported ISI value is specific to the PT reagent and instrument combination ("instrument-specific ISI"). In several studies, the accuracy of INR results was enhanced when instrument-specific ISI was used instead of the generic ISI.[10,11] The range of discrepancy between the manufacturer-derived ISI and the local validated ISI can vary between +15% and 30%, thus making clinically significant differences in the INR value. Therefore the ISI value should be verified, especially in laboratories using generic ISI values. If the local validated ISI value is significantly different from the reported ISI, then the ISI must be determined locally.
i Initially, the ISI is assigned by the manufacturer based on the WHO ISI IRP. The yellow-shaded area shows the validation of the ISI at the local laboratory level. Every new reagent lot must at least be verified by the local laboratory. For proper local verification, the locally determined ISI must agree within 15% to be acceptable. If greater than 15%, then the ISI must be locally calibrated and re-verified.
Initially, the ISI is assigned by the manufacturer based on the WHO ISI IRP. The yellow-shaded area shows the validation of the ISI at the local laboratory level. Every new reagent lot must at least be verified by the local laboratory. For proper local verification, the locally determined ISI must agree within 15% to be acceptable. If greater than 15%, then the ISI must be locally calibrated and re-verified.
The definition of verification is "the confirmation through the provision of objective evidence that the specified requirements have been fulfilled" (within a pre-established set of criteria).[2,9] Verification is usually a 1-time process completed to confirm test performance before the INR system is used for patient testing. If significant differences in the INR test system are present, then calibration is performed followed by repeating the verification process. Calibration is "a set of operations establishing, under specified conditions, the relationship between true quantitative values indicated by the measuring test system."[9] For the INR test system, if the verification is not different from the reported ISI value, then calibration does not need to be performed. If significant differences (>15%) are found between the ISI values, then calibration of the ISI is required, followed by re-verification to ensure INR accuracy.[9,10]
The local verification and calibration (if necessary) of the ISI is performed with FDA-approved kits that provide all of the certified plasmas, the procedure, and data calculations. This ISI verification can be performed by any technologist or supervisor in all laboratories performing patient PT/INR results. The procedure usually takes 3 days of performing PT/INR testing on the certified plasmas and about 20 to 30 minutes of calculations that can be performed either by the manufacturer of the kit or through the manufacturer's Web-based program. This local verification and calibration procedure should be included in all new reagent and/or instrument contracts, cost per test, and cost per reportable result contracts. International sensitivity index verification and calibration (if necessary) should be performed (as part of the contract) at installation of the instrument, when starting a new reagent, for lot changes, and after instrument repair or internal or external QC issues. The procedure itself is relatively straightforward and has safeguards built in to provide a more accurate local ISI with clinically correct INR values.
Verification of the ISI in the Local Laboratory
The laboratory should not accept the initial ISI value assigned by the manufacturer as the local laboratory's working parameters, and conditions may significantly affect the patient's calculated INR results. With this in mind, it becomes the laboratory's responsibility to verify the validity of the ISI (Table 2).[9]
Two basic methods for local verification of ISI are available.[9] The first is the impractical method of using the WHO standard protocol. It is not feasible since it requires fresh plasma samples, an IRP, and the ability to perform the labor-intensive tilt tube assays. The second, more practical method uses certified plasmas to determine the ISI. These plasmas are purchased from the manufacturer of the reagent system or from an independent vendor especially for the reagent system. The verification kit should be part of the validation process for new installations, new reagents, and changes in reagents lots (Table 2). The procedure for verification per the provided instructions must be followed. The verification kit should be FDA approved following the established guidelines of Clinical and Laboratory Standards Institute (CLSI).[2,9] In brief, the procedure requires a minimum of 3 certified plasmas in the range of 1.5 INR to 4.5 INR. These plasmas can be lyophilized or frozen. The certified plasmas are evaluated exactly as patient samples. The PT and INR values are determined for each plasma tested in duplicate once per day for 3 days. The INR values obtained are compared to the assigned INR of the certified plasma. If these values compare within 15%,[2,9] then the ISI has been verified, and the PT reagent can be used with the assigned ISI value. If the verification procedure fails (INR values >15%), then a local calibration must be performed (see below).[2,9] Table 3 and Table 4 show examples of a passing verification and a failing verification, respectively. In Table 3, the mean INR values are within 15% of the assigned value for all 3 plasmas, the ISI is verified, and the assigned ISI value is correct. In Table 4, the highest INR certified plasma failed verification (>15%), so the assigned ISI cannot be used, and local calibration must be performed to determine a local valid ISI.
Local System Calibration of the ISI for the Local Laboratory
If verification fails, then the laboratory must not report patient results until the correct ISI is determined.[9] The laboratory must establish that: 1) instrument(s) was(were) working properly; 2) reagents were reconstituted correctly; 3) MNPT was determined accurately (geometric mean); and 4) no clerical or mathematical errors were made. If these are correct, then proceed to local calibration of the ISI.
Local calibration can be accurately determined using 2 methods: 1) calculating a local ISI, or 2) generating a PT/INR calibration line on which PT values are read as the INR value.[9] Whichever method is used, the calibration kit must be FDA approved. The certified plasmas must be compatible for the reagents and instruments used in the laboratory.[9] As an example, if the laboratory is using recombinant human thromboplastin, the calibration kit should be certified for use with human thromboplastin. The local ISI calibration procedure is a modification of the WHO protocol.[8,9] The PT values for each of the certified plasmas are determined using the local PT reagent and instrument. The local PT values are plotted against the assigned PT values of the certified plasma and an orthogonal regression line is calculated. The ISI calibration is considered valid if the slope has a CV of <3%.[9] The resulting slope of the line is the correct local ISI.[8,9] The procedure is similar to the verification method. The certified plasmas must be run in duplicate for at least 3 days to account for variation due to random error.
The necessary number of certified plasmas depends on a variety of factors, such as the source of the plasma (immuno-depleted or treated individual), type of plasma (frozen or lyophilized), single donor or multiple donors, and the IRP used for the certification of the plasma.[9] The manufacturer of the calibration kit in consultation with and approval by the FDA has determined the minimum number of certified plasmas needed. Most manufacturers will help the local laboratory determine the ISI value through either the Internet or as a "send-in" service. The manufacturer must provide detailed documentation of these ISI determination calculations for accreditation documentation. Of important note, after local calibration, the ISI must again be re-validated to confirm that the calibration and changed ISI are truly correct.
The second method to determine the local ISI is the direct INR calibration line, which is independent of the ISI value and the MNPT.[9] A disadvantage of this method is that many laboratory information systems and/or instrument systems are not programmed for calculating the INR by this method. Using this protocol, the PT values of certified plasmas are determined using the laboratory's system, also testing for 3 days in duplicate. The PT values determined locally are plotted on the y axis against the assigned certified plasma INR values (x axis). Using orthogonal regression, the best fit line is plotted. For a valid calibration curve, the r2 value of the regression line must be >0.95. The patient's INR is mathematically or graphically determined from this calibration line. Significant changes in the reagent-instrument system, such as lot changes, instrumentation repair, QC validity changes, and proficiency testing problems will all require establishing the INR calibration line and recertification
The INR is an important clinical tool for monitoring AVK therapy. The introduction of the INR has added several orders of magnitude of accuracy to anticoagulant monitoring. Still, more accuracy is needed to further reduce clinical problems associated with anticoagulation. To this end, the development of local reagent accuracy through the use of local ISI verification and ISI calibration adds even greater confidence to the correct reporting of INR values. The methods for ISI verification and the local ISI calibrations are just beginning to be used in the United States. The College of American Pathologists (CAP) Laboratory Accreditation program checklist (HEM.23220) requires documentation that the ISI is validated. The local ISI verification and calibration method fulfills that requirement. The methods may appear complex and the mathematics difficult, but kit manufacturers should assist with these calculations. Local determination of the ISI will significantly increase clinical confidence in oral anticoagulant monitoring.
Tuesday, March 1, 2011
WORK SMARTER NOT HARDER
1) Aim for effectiveness, not neatness. Neatness as an end in itself can even be risky: Putting things away just to clear off your desk can cause you to lose or forget them.
2) Clutter is rarely caused by insufficient space or time. The culprit is usually indecisiveness. So be selective about what you bring into your office and home. If you know what you value and what your goals are, being selective is not hard.
3) Have a place for everything. Open your mail in the same place everyday so it doesn't get strewn everywhere. Put unpaid bills together, separate from paid bills. Store all office supplies together to prevent duplicate purchases.
4) Do not use your entire desk surface as a giant In-box. Instead, determine your next action on every piece of paper and file accordingly. Tasks to be done soon (phone calls to make, questions to ask business associates) and current projects go into your "Action Files," which should not be mixed with Reference Files. Action Files must be kept close at hand.
5) That maxim, "Handle each piece of paper only once," is too extreme to be realistic. But it contains a grain of truth. Do try to take the next action that's required each time you handle a piece of paper. How about that seminar advertisement you left on your desk, as a reminder to decide whether to sign up -- you know, that paper you've shuffled ten times today already? Either call right now to get the information you need, or make a note in your appointment book to call later. Then you're that much closer to being done with it.
6) Don't save paper that you're not willing to spend time filing. If you don't file it properly, you either will forget you have it, or you won't be able to find it when you need it. It does you no good, and the result is the same as if you'd thrown it out in the first place. If you are set up to scan information into your computer, be selective. If you cannot imagine a specific situation when you'd need to refer to the information again, don't scan it. Most of us save a great deal of paper we'll never use again.
7) Use your day planner to help clear your desk. If you avoid filing things out of fear you'll forget to follow up, jot down a reminder in your appointment book or computer software.
8) Often we are own worst enemies, interrupting ourselves by jumping from one half-finished task to another. Stop doing "the desktop shuffle" - moving papers aimlessly around on your desk. Every time you handle an item, take an action towards completing it.
9) Learn to say "No." You could live to be a hundred and still not have time to do everything you want---that's the curse and blessing of being intelligent and having high expectations of yourself. The good news is you can choose what to focus on. You have far more freedom than you may realize. Aside from obligations like caring for vulnerable family members and paying taxes, very little of what you "have" to do is morally or legally mandatory. Review everything in your life and ask, "What's the worst that can happen if I stopped doing this?" Saying "No" sometimes is the only way you can "Yes" to what you really value.
10) Beware of stuff. The more stuff you have, the more you must find a place to put, and the more you'll have to clean, repair, and eventually replace. Stop buying things you don't really need just because they're on sale. You can always get more stuff, and you can always get more money. But you can never get more time.
11) Do buy more of things you use continually. Frantic last-minute shopping trips can be averted by purchasing things before your supply runs out.
12) Schedule appointments with yourself to get things done. Appointments aren't only for business lunches or seeing your doctor. They're for you, too. Commit to spending time on the things you keep "not getting around to." This works for everything -- from taking the next step on that back-burner project, to making sure you get yourself to the gym twice a week.
13) Beware of perfectionism. Most routine work doesn't need to be done perfectly. Ask yourself -- Is your effort disproportionate to the value of the task? Will other, more important projects be delayed as a result? Can you reduce the frequency or level of detail of this task?
Haiti's Cholera Outbreak
February 11, 2011 (Vienna, Austria) — The cholera epidemic that developed in Haiti became a multifocal event as it spread throughout South America, due to factors such as air travel and immigration that act as "vectors" of infectious disease, a new report suggests.
The findings were reported by Jennifer Malaty, from the Georgetown University Medical Center, in Arlington, Virginia, here at the IMED 2011: International Meeting on Emerging Diseases and Surveillance.
"Cholera's sudden emergence in the Americas and the Caribbean after 100 years of silence was a tragic reminder of how mobile pathogens have become," Ms. Malaty told Medscape Medical News. "The [Haitian] population also had the disadvantage of being immunologically naïve," she said.
According to the researchers, local laboratories confirmed that the form of cholera detected in Haiti is commonly found in South Asia and Africa, and that the outbreak originated from contaminated water near a facility that housed Nepalese troops.
Subsequent to the cholera outbreak in Haiti, the migration of humans led to sporadic clusters of cholera cases in new and previously unaffected regions.
By November 16, 2009, the Dominican Republic detected its first case of cholera in a migrant worker who had returned home from Haiti after the outbreak.
Suspected cases of cholera have since been reported in Bolivia, Brazil, Chile, Colombia, Nicaragua, Panama, Peru, and Venezuela. Confirmed imported cases have been reported in Florida. The CDC has reported 13 suspected imported cases, with 5 confirmed as of December 2010.
Based on models of previous cholera spread, the researchers estimate that up to 200,000 cases could arise in the Caribbean in the next 18 months.
"International bonds, the ease of direct flights, and better medical and professional opportunities abroad [compared with in Haiti] have turned the cholera outbreak into a multifocal disease event," the researchers conclude.
According to Ms. Malaty, the study of emerging outbreaks must have both a microscope and a macroscope. Although there is value in case counts and case fatality ratios, diseases are never bound by national borders, she said.
"Biosurveillance is a multidisciplinary field that is influenced by culture, language, history, economics, and sadly, politics," she added. "Monitoring of diseases must be flexible, both in sources of data and in analysis."
Scott F. Dowell, MD, MPH, from the CDC's Division of Global Disease Detection and Emergency Response, and colleagues from the CDC recently authored a Perspective in the New England Journal of Medicine (2011;364:300-301). According to Dr. Dowell and colleagues, when cholera struck in mid-October, it "moved easily from sewage to drinking water sources and spread within 2 months to all departments (provinces) of the country, sickening more than 170,000 people and killing more than 3,600 by December 31, 2010."
"Cholera spreads easily across international borders, and it is likely that occasional importations to other countries in the region will continue," Dr. Dowell told Medscape Medical News. "Fortunately, it is unlikely to cause epidemic disease in places like Florida, where clean water and improved sanitation systems are in place."
He added that "clinicians in the region should remain aware of the possibility of importation, take careful travel histories, recognize the clinical features of cholera and the potential for rapid and dangerous dehydration, and be prepared to treat individual cases and report them to the local public health authorities."
According to the CDC, rehydration is the cornerstone of treatment for cholera. Oral rehydration salts and, when necessary, intravenous fluids and electrolytes, if administered in a timely manner and in adequate volumes, will reduce fatalities to well below 1%. In addition, antibiotics, indicated in severe cases, reduce fluid requirements and duration of illness.
The findings were reported by Jennifer Malaty, from the Georgetown University Medical Center, in Arlington, Virginia, here at the IMED 2011: International Meeting on Emerging Diseases and Surveillance.
"Cholera's sudden emergence in the Americas and the Caribbean after 100 years of silence was a tragic reminder of how mobile pathogens have become," Ms. Malaty told Medscape Medical News. "The [Haitian] population also had the disadvantage of being immunologically naïve," she said.
According to the researchers, local laboratories confirmed that the form of cholera detected in Haiti is commonly found in South Asia and Africa, and that the outbreak originated from contaminated water near a facility that housed Nepalese troops.
Subsequent to the cholera outbreak in Haiti, the migration of humans led to sporadic clusters of cholera cases in new and previously unaffected regions.
By November 16, 2009, the Dominican Republic detected its first case of cholera in a migrant worker who had returned home from Haiti after the outbreak.
Suspected cases of cholera have since been reported in Bolivia, Brazil, Chile, Colombia, Nicaragua, Panama, Peru, and Venezuela. Confirmed imported cases have been reported in Florida. The CDC has reported 13 suspected imported cases, with 5 confirmed as of December 2010.
Based on models of previous cholera spread, the researchers estimate that up to 200,000 cases could arise in the Caribbean in the next 18 months.
"International bonds, the ease of direct flights, and better medical and professional opportunities abroad [compared with in Haiti] have turned the cholera outbreak into a multifocal disease event," the researchers conclude.
According to Ms. Malaty, the study of emerging outbreaks must have both a microscope and a macroscope. Although there is value in case counts and case fatality ratios, diseases are never bound by national borders, she said.
"Biosurveillance is a multidisciplinary field that is influenced by culture, language, history, economics, and sadly, politics," she added. "Monitoring of diseases must be flexible, both in sources of data and in analysis."
Scott F. Dowell, MD, MPH, from the CDC's Division of Global Disease Detection and Emergency Response, and colleagues from the CDC recently authored a Perspective in the New England Journal of Medicine (2011;364:300-301). According to Dr. Dowell and colleagues, when cholera struck in mid-October, it "moved easily from sewage to drinking water sources and spread within 2 months to all departments (provinces) of the country, sickening more than 170,000 people and killing more than 3,600 by December 31, 2010."
"Cholera spreads easily across international borders, and it is likely that occasional importations to other countries in the region will continue," Dr. Dowell told Medscape Medical News. "Fortunately, it is unlikely to cause epidemic disease in places like Florida, where clean water and improved sanitation systems are in place."
He added that "clinicians in the region should remain aware of the possibility of importation, take careful travel histories, recognize the clinical features of cholera and the potential for rapid and dangerous dehydration, and be prepared to treat individual cases and report them to the local public health authorities."
According to the CDC, rehydration is the cornerstone of treatment for cholera. Oral rehydration salts and, when necessary, intravenous fluids and electrolytes, if administered in a timely manner and in adequate volumes, will reduce fatalities to well below 1%. In addition, antibiotics, indicated in severe cases, reduce fluid requirements and duration of illness.
Haiti's Cholera Outbreak
February 11, 2011 (Vienna, Austria) — The cholera epidemic that developed in Haiti became a multifocal event as it spread throughout South America, due to factors such as air travel and immigration that act as "vectors" of infectious disease, a new report suggests.
The findings were reported by Jennifer Malaty, from the Georgetown University Medical Center, in Arlington, Virginia, here at the IMED 2011: International Meeting on Emerging Diseases and Surveillance.
"Cholera's sudden emergence in the Americas and the Caribbean after 100 years of silence was a tragic reminder of how mobile pathogens have become," Ms. Malaty told Medscape Medical News. "The [Haitian] population also had the disadvantage of being immunologically naïve," she said.
According to the researchers, local laboratories confirmed that the form of cholera detected in Haiti is commonly found in South Asia and Africa, and that the outbreak originated from contaminated water near a facility that housed Nepalese troops.
Subsequent to the cholera outbreak in Haiti, the migration of humans led to sporadic clusters of cholera cases in new and previously unaffected regions.
By November 16, 2009, the Dominican Republic detected its first case of cholera in a migrant worker who had returned home from Haiti after the outbreak.
Suspected cases of cholera have since been reported in Bolivia, Brazil, Chile, Colombia, Nicaragua, Panama, Peru, and Venezuela. Confirmed imported cases have been reported in Florida. The CDC has reported 13 suspected imported cases, with 5 confirmed as of December 2010.
Based on models of previous cholera spread, the researchers estimate that up to 200,000 cases could arise in the Caribbean in the next 18 months.
"International bonds, the ease of direct flights, and better medical and professional opportunities abroad [compared with in Haiti] have turned the cholera outbreak into a multifocal disease event," the researchers conclude.
According to Ms. Malaty, the study of emerging outbreaks must have both a microscope and a macroscope. Although there is value in case counts and case fatality ratios, diseases are never bound by national borders, she said.
"Biosurveillance is a multidisciplinary field that is influenced by culture, language, history, economics, and sadly, politics," she added. "Monitoring of diseases must be flexible, both in sources of data and in analysis."
Scott F. Dowell, MD, MPH, from the CDC's Division of Global Disease Detection and Emergency Response, and colleagues from the CDC recently authored a Perspective in the New England Journal of Medicine (2011;364:300-301). According to Dr. Dowell and colleagues, when cholera struck in mid-October, it "moved easily from sewage to drinking water sources and spread within 2 months to all departments (provinces) of the country, sickening more than 170,000 people and killing more than 3,600 by December 31, 2010."
"Cholera spreads easily across international borders, and it is likely that occasional importations to other countries in the region will continue," Dr. Dowell told Medscape Medical News. "Fortunately, it is unlikely to cause epidemic disease in places like Florida, where clean water and improved sanitation systems are in place."
He added that "clinicians in the region should remain aware of the possibility of importation, take careful travel histories, recognize the clinical features of cholera and the potential for rapid and dangerous dehydration, and be prepared to treat individual cases and report them to the local public health authorities."
According to the CDC, rehydration is the cornerstone of treatment for cholera. Oral rehydration salts and, when necessary, intravenous fluids and electrolytes, if administered in a timely manner and in adequate volumes, will reduce fatalities to well below 1%. In addition, antibiotics, indicated in severe cases, reduce fluid requirements and duration of illness.
The findings were reported by Jennifer Malaty, from the Georgetown University Medical Center, in Arlington, Virginia, here at the IMED 2011: International Meeting on Emerging Diseases and Surveillance.
"Cholera's sudden emergence in the Americas and the Caribbean after 100 years of silence was a tragic reminder of how mobile pathogens have become," Ms. Malaty told Medscape Medical News. "The [Haitian] population also had the disadvantage of being immunologically naïve," she said.
According to the researchers, local laboratories confirmed that the form of cholera detected in Haiti is commonly found in South Asia and Africa, and that the outbreak originated from contaminated water near a facility that housed Nepalese troops.
Subsequent to the cholera outbreak in Haiti, the migration of humans led to sporadic clusters of cholera cases in new and previously unaffected regions.
By November 16, 2009, the Dominican Republic detected its first case of cholera in a migrant worker who had returned home from Haiti after the outbreak.
Suspected cases of cholera have since been reported in Bolivia, Brazil, Chile, Colombia, Nicaragua, Panama, Peru, and Venezuela. Confirmed imported cases have been reported in Florida. The CDC has reported 13 suspected imported cases, with 5 confirmed as of December 2010.
Based on models of previous cholera spread, the researchers estimate that up to 200,000 cases could arise in the Caribbean in the next 18 months.
"International bonds, the ease of direct flights, and better medical and professional opportunities abroad [compared with in Haiti] have turned the cholera outbreak into a multifocal disease event," the researchers conclude.
According to Ms. Malaty, the study of emerging outbreaks must have both a microscope and a macroscope. Although there is value in case counts and case fatality ratios, diseases are never bound by national borders, she said.
"Biosurveillance is a multidisciplinary field that is influenced by culture, language, history, economics, and sadly, politics," she added. "Monitoring of diseases must be flexible, both in sources of data and in analysis."
Scott F. Dowell, MD, MPH, from the CDC's Division of Global Disease Detection and Emergency Response, and colleagues from the CDC recently authored a Perspective in the New England Journal of Medicine (2011;364:300-301). According to Dr. Dowell and colleagues, when cholera struck in mid-October, it "moved easily from sewage to drinking water sources and spread within 2 months to all departments (provinces) of the country, sickening more than 170,000 people and killing more than 3,600 by December 31, 2010."
"Cholera spreads easily across international borders, and it is likely that occasional importations to other countries in the region will continue," Dr. Dowell told Medscape Medical News. "Fortunately, it is unlikely to cause epidemic disease in places like Florida, where clean water and improved sanitation systems are in place."
He added that "clinicians in the region should remain aware of the possibility of importation, take careful travel histories, recognize the clinical features of cholera and the potential for rapid and dangerous dehydration, and be prepared to treat individual cases and report them to the local public health authorities."
According to the CDC, rehydration is the cornerstone of treatment for cholera. Oral rehydration salts and, when necessary, intravenous fluids and electrolytes, if administered in a timely manner and in adequate volumes, will reduce fatalities to well below 1%. In addition, antibiotics, indicated in severe cases, reduce fluid requirements and duration of illness.
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