Healthcare analytics, AI solutions for biological big data, providing an AI platform for the biotech, life sciences, medical and pharmaceutical industries, as well as for related technological approaches, i.e., curation and text analysis with machine learning and other activities related to AI applications to these industries.
Today’s fundamental challenge in Prostate cancer screening
Author and Curator: Dror Nir, PhD
Article 8.2.Todays fundamental challenge in Prostate cancer screening
The management of men with prostate cancer is becoming one of the most challenging public health issues in the Western world. It is characterized by: over-diagnosis; over-treatment; low treatment efficacy; treatment related toxicity; escalating cost; and unsustainability [Bangma et al, 2007; Esserman et al, 2009]. How come? Well, everyone accepts that most prostate cancers are clinically insignificant. It is well known that all men above 65 harbor some sort of prostate cancer. Due to the current aggressive PSA-based screening, one in six men will be diagnosed with prostate cancer. Yet, the lifetime risk of dying of prostate cancer is only 3%. The problem is that, once diagnosed with prostate cancer, there is no accurate tool to identify those men that will die of the disease (in my previous post I mentioned 1:37). Currently, screening practices for prostate cancer are relying on the very unspecific prostate-specific-antigen (PSA) bio-marker test to determine which men are at higher risk of harboring prostate cancer and therefore need a biopsy. The existing diagnostic test is a transrectal ultrasound (TRUS) guided prostate biopsy aimed at extracting representative tissue from areas where cancer usually resides. This procedure suffers from several obvious faults:
1. Since the imaging tool used (B-mode ultrasound) is poor at detecting malignancies in the prostate, the probability of hitting a clinically significant cancer or missing a clinically insignificant cancer is subject to random error.
2. TRUS biopsy is also subjected to systematic error as it misses large parts of the prostate which might harbor cancer (e.g. apex and anterior zones). 3. TRUS guided biopsies are often unrepresentative of the true burden of cancer as either the volume or grade of cancer can be underestimated.
In the last ten years I was leading the development of an innovative ultrasound-based technology, HistoScanningTM, aimed at improving the aforementioned faults;
In my future posts I will go into more detail on how these imaging modalities fit into routine workflow, how much they stay within budget constraints and what level of promise they bear for promoting personalized medicine. Stay tuned… Footnote: According to the final report by an advisory panel to the USA government: Doctors should no longer offer the PSA prostate cancer screening test to healthy men because they’re more likely to be harmed by the blood draw, and the chain of medical interventions that often follows than be helped; (http://www.usatoday.com/news/health/story/2012-05-21/prostate-cancer-screening-test-harmful/55118036/1)But then; what should be offered instead?
Other posts on this Scientific Website addressing Prostate Cancer
Prostate Cancers Plunged After USPSTF Guidance, Will It Happen Again?
Aspirin-clopidogrel combination no better than aspirin alone.
Antiplatelet drugs such as aspirin are routinely prescribed to help prevent new strokes in people with a history of lacunar stroke. The Secondary Prevention of Small Subcortical Strokes (SPS3) trial was designed to determine if adding clopidogrel to aspirin would offer better protection than aspirin alone. The results appear in the Aug. 30th New England Journal of Medicine.* They show that the aspirin-clopidogrel combination was about equal to aspirin in reducing the risk of any type of stroke, but it almost doubled the risk of gastrointestinal bleeding.
“For all stroke therapeutics, there is a need to balance the potential benefits against the risks. The SPS3 findings establish that for lacunar stroke, dual therapy with aspirin and clopidogrel carries significant risk and minimal benefit,” said Walter Koroshetz, M.D., deputy director of National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.
In addition to comparing dual antiplatelet therapy with aspirin, the trial was designed to test two levels of blood pressure control. After an interim data analysis in August 2011, the antiplatelet component of the trial was stopped. NIH also issued a clinical alert, warning that there was “little likelihood of benefit in favor of aspirin plus clopidogrel [for] recurrent stroke should the study continue to conclusion.” The blood pressure component of the trial is ongoing, and the trial participants have been encouraged to continue taking aspirin without clopidogrel.
Strokes occur when blood vessels that supply the brain rupture or become blocked, such as by a blood clot. Antiplatelet drugs interfere with the formation of blood clots.
Lacunar strokes occur due to chronic high blood pressure, which in turn leads to progressive narrowing and finally blockage of small arteries that supply deep brain structures. They account for up to one-fifth of all strokes and are especially common among African-Americans, Hispanics and people with diabetes. Although lacunar strokes tend to produce relatively small lesions, they can cause disability depending on where they occur in the brain.
The SPS3 trial involves more than 3,000 participants at 82 clinical centers in North and South America and in Spain. The participants are age 30 and older, and all had a recent history of lacunar stroke prior to enrollment. About 52 percent are white, 31 percent Hispanic and 17 percent black.
For the antiplatelet component of the trial, about half of the participants received 325 milligrams of aspirin and 75 milligrams of clopidogrel daily, and the other half received aspirin and placebo. The participants were also randomly assigned to receive either standard control of systolic blood pressure (less than 130 mm Hg) or aggressive control (130-149 mm Hg).
After eight years of study, the annual risk of recurrent stroke was 2.7 percent in the aspirin-only group and 2.5 percent in the aspirin plus clopidogrel group. Most of the recurrent strokes in both groups were lacunar strokes. The rate of serious or life-threatening internal bleeding was 1.1 percent in the aspirin group and 2.1 percent in the dual therapy group. The difference was due mostly to a higher number of gastrointestinal bleeds in the dual therapy group. The percentage of brain bleeds in the two groups was not significantly different. Deaths from any cause were also higher in the aspirin-clopidogrel group.
For both groups, stroke recurrence was lower than the investigators had expected. When the SPS3 trial began in 2003, another large trial that tested warfarin vs. aspirin for stroke prevention had just ended. Warfarin is an anticoagulant, another class of drugs that interferes with blood clotting. That trial, called the Warfarin vs. Aspirin Recurrent Stroke Study (WARSS), found that patients with a history of lacunar strokes who took aspirin had an annual stroke recurrence rate of about 7 percent. (Warfarin and aspirin were about equal.)
This reflects a common trend, Dr. Benavente said. “What we see more and more often in stroke prevention trials is a significant decrease in stroke risk, compared to data from 10 years ago. We have better medications now to control stroke risk factors such as high blood pressure and cholesterol, and these are clearly having an impact.”
In prior studies, antiplatelet drugs including aspirin or clopidogrel alone, or a combination of aspirin and dipyridamole, have been shown to reduce stroke risk in patients with heart disease or prior stroke. In one trial, aspirin combined with clopidogrel was more effective than aspirin alone at reducing stroke risk in patients with atrial fibrillation, a type of abnormal heart rhythm. However, other trials involving broader stroke populations found no added benefit from combining aspirin and clopidogrel. Therefore, current practice guidelines recommend aspirin alone, clopidogrel alone, or aspirin plus dipyridamole for secondary prevention after most types of stroke. The SPS3 results are consistent with those guidelines.
Researchers continue to investigate whether the clopidogrel-aspirin combination might be beneficial for patients with other types of stroke, such as transient ischemic attack (TIA). This is a type of stroke in which symptoms fade away in less than 24 hours; it is also a warning that a more damaging stroke may be imminent. The Platelet-Oriented Inhibition in New TIA (POINT) trial is testing whether aspirin plus clopidogrel are effective at preventing major strokes when given within 12 hours of a TIA. That trial is also funded by NINDS.
WOEST (What is the Optimal Antiplatelet and Anticoagulant Therapy in Patients with Oral Anticoagulantion and Coronary Stenting): Get Rid Of The Aspirin In Triple Therapy
According to current guidelines and clinical practice, PCI patients already taking an oral anticoagulant generally end up on triple therapy comprising the anticoagulant plus clopidogrel and aspirin. However, there is no supporting evidence base for this approach and the triple therapy regimen is known to increase bleeding complications. Now a new study– the first randomized trial to address this situation, according to the investigators– may have a large impact on clinical practice by demonstrating that the omission of aspirin in this context appears to be safe and may reduce adverse events.
Results of the WOEST (What is the Optimal Antiplatelet and Anticoagulant Therapy in Patients with Oral Anticoagulantion and Coronary Stenting) trial were presented by Willem Dewilde at the ESC in Munich today. Investigators in the Netherlands and Belgium randomized 573 patients to triple therapy or dual therapy of an anticoagulant plus clopidogrel for at least one month after implantation of a bare-metal stent or one year after a drug-eluting stent. Two-thirds of the patients were receiving oral anticoagulation for atrial fibrillation.
The primary endpoint, the total number of bleeding events, was dramatically reduced in the dual therapy group at one year:
44.9% in the triple therapy group versus 19.5% (HR 0.36, CI 0.26-0.50)
There were 3 intracranial bleeds in each group. Most of the difference in bleeding occurred in TIMI minor and minimal bleeding. The difference in TIMI major bleeding (3.3% versus 5.8%) did not achieve statistical significance.
Clinical events, the trials’s secondary endpoint, were numerically lower in the dual therapy group. The difference in mortality achieved statistical significance.
Mortality: 7 deaths (2.6%) in the dual therapy group versus 18 deaths (6.4%) in the triple therapy group, p=0.027
MI: 3.3% versus 4.7%, p=0.382
TVR: 7.3% versus 6.8%, p=0.876
Stroke: 1.1% versus 2.9%, p=0.128)
Stent thrombosis: 1.5% versus 3.2%, p=0.165
“The WOEST study demonstrates that omitting aspirin leads to less bleedings but does not increase the risk of stent thrombosis, stroke or myocardial infarction,” said Dewilde in an ESC press release. “Although the number of patients in the trial is limited, this is an important finding with implications for future treatment and guidelines in this group of patients known to be at high risk of bleeding and thrombotic complications.”
David Holmes said the trial addressed “an incredibly important issue” and predicted that it would “change the way we practice medicine, it will change practice right away.” Keith Fox said that the evidence base prior to WOEST was extremely limited and that the trial showed that there was no hazard in doing without aspirin. The ESC discussant, Marco Valgimigli, said the trial showed it was safe to drop aspirin and provided another demonstration that “we have hit the wall” with anticoagulation.
Republished with permission from CardioExchange, a NEJM group publication.
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco
MUNICH — For patients with unstable angina or non-ST-segment elevation myocardial infarction (non-STEMI) who do not undergo revascularization, increasing platelet inhibition may not improve outcomes, a randomized trial showed.
Added to a background of low-dose aspirin, prasugrel (Effient) did not significantly reduce the rate of MI, stroke, or cardiovascular death compared with clopidogrel (13.9% versus 16%, HR 0.91, 95% CI 0.79 to 1.05), according to Matthew Roe, MD, of Duke University in Durham, N.C.
The risk of severe bleeding was similar with both drugs, although minor and moderate bleeding were increased with prasugrel, Roe reported at the European Society of Cardiology meeting here. The findings were published simultaneously online in the New England Journal of Medicine.
“I think the outcome is a bit surprising because we think usually that more aggressive antiplatelet therapy, conceivably, in the face of an acute coronary syndrome and non-ST-elevation would lead to lesser adverse outcome from acute myocardial infarction or death,” said William Zoghbi, MD, from Methodist DeBakey Heart Center in Houston and president of the American College of Cardiology.
But he said clinicians need to respect the data “and start thinking about pathogenesis and what we’re trying to do with any of our new interventions.”
In patients with unstable angina or non-STEMI, practice guidelines call for angiography within 48 to 72 hours with provisional revascularization. Many of these patients do not ultimately undergo revascularization, placing them at greater risk compared with those who have their arteries opened with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG).
Recommended medical therapy is with clopidogrel and aspirin, which is an approach that will not change from the current findings, Zoghbi said.
The purpose of the TRILOGY ACS trial was to explore whether using a more powerful platelet inhibitor — prasugrel — would improve outcomes compared clopidogrel (Plavix) in this high-risk patient subset.
The primary analysis involved 7,243 patients younger than 75 (mean age 62) who were receiving aspirin and were randomized to prasugrel 10 mg daily (or 5 mg daily for those weighing less than 132 pounds) or to clopidogrel 75 mg daily. The researchers recommended a daily aspirin dose of 100 mg or less.
A secondary, exploratory analysis involved 2,083 patients, 75 or older, who were randomized to prasugrel 5 mg daily or to clopidogrel 75 mg daily.
The lack of efficacy seen in the primary analysis of patients younger than 75 remained when patients of all ages were combined. There were no between-group differences for any of the components of the primary endpoint.
A prespecified secondary analysis taking multiple recurrent ischemic events into consideration showed a lower risk of MI, stroke, and cardiovascular death with prasugrel in the younger patients (HR 0.85, 95% CI 0.72 to 1.00, P=0.04), a finding consistent with the main results of the TRITON-TIMI 38 trial, which involved patients treated with PCI. The apparent benefit appeared after 12 months of treatment.
“Although this observation is exploratory, it raises the question of whether investigation of the multiplicity of ischemic events is warranted in future secondary-prevention trials, rather than solely analyzing the time to the first event, as has been traditional in studies involving patients who have had an acute coronary event,”the researchers wrote.
Rates of GUSTO severe or life threatening bleeding and TIMI major bleeding — as well as intracranial hemorrhage — were similar in the two groups in both the younger patients and in the overall study population. When minor and moderate bleeding events were added, the bleeding rate was higher with prasugrel.
There were no widespread differences between the groups in rates of nonhemorrhagic serious adverse events, but heart failure was more frequent with clopidogrel (1.8% versus 1.3%, P=0.045).
Douglas Weaver, MD, of Henry Ford Health System, said that he does not think the findings will have any impact on the use of prasugrel, which is not indicated for the patient population included in the study.
“It just doesn’t pass muster in improving value over clopidogrel,” said Weaver, a past president of the American College of Cardiology.
From a clinical perspective, he said, an important message from the study is the evidence of the safety of a reduced dose of prasugrel in the patients 75 and older, which is a consideration when prescribing prasugrel for patients undergoing PCI.
In comments following Roe’s presentation, Raffaele De Caterina, MD, PhD, of the G. d’Annunzio University in Chieti, Italy, provided context about how the findings fit in with the rest of the literature.
He compared the current results to those of a substudy of the PLATO trial, which involved ticagrelor (Brilinta).
In that trial, ticagrelor significantly reduced vascular death, MI, and stroke (HR 0.85, 95% CI 0.73 to 1.00, P=0.045) — the primary endpoint — and all-cause death (HR 0.75, 95% CI 0.61 to 0.93).
He then highlighted the ESC guidelines on treating patients with acute coronary syndromes without persistent ST-segment elevation.
In those, ticagrelor is recommended for all patients at moderate-to-high risk of ischemic events, regardless of initial treatment strategy and including those pre-treated with clopidogrel, and prasugrel is recommended for those who have not taken another P2Y12 inhibitor, who have a known coronary anatomy, and who are proceeding to PCI.
“I believe such statements and recommendations of the guidelines should not be changed,” De Caterina said.
Roe reported relationships with Daiichi Sankyo, Eli Lilly, AstraZeneca, Bristol-Myers Squibb, Janssen Pharmaceuticals, Merck, Hoffmann-La Roche, and sanofi-aventis. The other authors reported numerous relationships with industry.
Prematurely halted ALTITUDE trial showed When added to monotherapy with either an ACE inhibitor or an angiotensin receptor blocker (ARB), aliskiren (Tekturna) did not improve outcomes in patients with type 2 diabetes who had high cardiovascular and renal risk
ESC: Aliskiren Onboard No Help in T2D
By Todd Neale, Senior Staff Writer, MedPage Today
Published: August 26, 2012
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco
MUNICH — When added to monotherapy with either an ACE inhibitor or an angiotensin receptor blocker (ARB), aliskiren (Tekturna) did not improve outcomes in patients with type 2 diabetes who had high cardiovascular and renal risk, the prematurely halted ALTITUDE trial showed.
Through an average follow-up of 32 months, a composite of various cardiovascular and renal outcomes occurred in 17.9% of patients receiving the direct renin inhibitor and 16.8% of those receiving placebo (HR 1.08, 95% CI 0.98 to 1.20), according to Hans-Henrik Parving, MD, DMSc, of the University of Copenhagen and Aarhus University in Denmark.
As a Hot Line presentation European Society of Cardiology meeting here, Parving reported that there were no significant differences on any of the individual components of the endpoint — cardiovascular death, resuscitated sudden death, MI, stroke, unplanned hospitalization for heart failure, doubling of baseline serum creatinine, and onset of end-stage renal disease — or all-cause death.
The rate of stroke — mostly ischemic stroke — was numerically higher with aliskiren, although the result fell short of statistical significance (3.4% versus 2.8%; HR 1.25, 95% CI 0.98 to 1.60,P=0.07).
Thus, Parving said, using aliskiren with ACE inhibitors or ARBs in these high-risk patients “is not recommended and may even be harmful.”
The data monitoring committee for the ALTITUDE trial decided to stop the study early in December 2011 both for futility and for adverse events. Then, earlier this year, the FDA issued a warning about using aliskiren with ACE inhibitors or ARBs and changed the drug label to reflect a contraindication for such combinations in patients with diabetes or renal impairment.
The trial included 8,561 patients with type 2 diabetes who had a high risk of cardiovascular or renal disease who were randomized to aliskiren — at 150 mg daily for 1 month followed by 300 mg daily thereafter — or placebo in addition to monotherapy with either an ACE inhibitor or an ARB (but not both).
Adding aliskiren did not improve outcomes, and in fact, may have caused harm, Parving said, as indicated by the apparent increase in stroke risk.
He said that could be explained by the impaired autoregulation of patients with diabetes or by chance, as there are no indications of a stroke risk in other studies of the drug.
Johannes Mann, of Friedrich Alexander University in Erlangen, Germany, and McMaster University in Hamilton, Ontario, who served as the discussant following Parving’s presentation, agreed that it could be a chance finding, but said that it could also be a direct effect of aliskiren itself.
He concluded that the stroke risk was not explained, however, by dual renin system inhibition, because such a signal was not seen in the ONTARGET trial, which compared the combination of ramipril (an ACE inhibitor) and telmisartan (an ARB) with each drug as monotherapy.
As noted when the trial was halted last year, adverse events were more frequent in the aliskiren group.
The percentage of patients who had a potassium level of 5.5 to less than 6.0 mmol/L was greater with active treatment (21% versus 16%), as was the percentage of those with a potassium level of 6.0 mmol/L or greater (8.8% versus 5.6%).
Aliskiren carried higher risks of hyperkalemia (38.7% versus 28.6%), hypotension (12.1% versus 8%), diarrhea (9.6% versus 7.2%), and falls (2.8% versus 2.6%). There was one death caused by hyperkalemia.
Douglas Weaver, MD, of the Henry Ford Health System in Detroit, said that the findings were disappointing, but that they likely wouldn’t change how aliskiren is used in practice.
“I don’t think this is going to have a negative or a positive effect on it,” said Weaver, who is a past president of the American College of Cardiology.
ALTITUDE was sponsored by Novartis Pharma AG.
The executive committee and other investigators or their institutions received a consultancy fee. Some of the authors are employees of Novartis and therefore eligible for stock and stock options.
Primary source: European Society of Cardiology
Source reference:
Parving H-H, et al “The Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)” ESC 2012; Abstract 399.
Aliskiren (INN) (trade names Tekturna, U.S.; Rasilez, U.K. and elsewhere) is the first in a class of drugs called direct renin inhibitors. Its current licensed indication is essential (primary) hypertension.
In December 2011, Novartis had to halt a clinical trial of the drug after discovering increased incidence of non-fatal stroke, renal complications, hyperkalemia and hypotension in patients with diabetes and renal impairment.[4]
The following recommendations are being added to the drug labels for aliskiren-containing products as of 4/20/12:
I) A new contraindication against the use of aliskiren with ARBs or ACEIs in patients with diabetes because of the risk of renal impairment, hypotension, and hyperkalemia. II) A warning to avoid use of aliskiren with ARBs or ACEIs in patients with moderate to severe renal impairment (i.e., where glomerular filtration rate [GFR] < 60 mL/min).
Mechanism of Action
Renin is the first enzyme in the renin-angiotensin-aldosterone system which plays a role in blood pressure control. Renin cleaves angiotensinogen to angiotensin I, which is in turn converted by angiotensin-converting enzyme (ACE) toangiotensin II. Angiotensin II has both direct and indirect effects on blood pressure. It directly causes arterial smooth muscle to contract, leading to vasoconstriction and increased blood pressure. Angiotensin II also stimulates the production of aldosterone from the adrenal cortex, which causes the tubules of the kidneys to increase reabsorption of sodium, with water following thereby increasing plasma volume and blood pressure.
Aliskiren binds to the S3bp binding pocket of renin, essential for its activity.[5] Binding to this pocket prevents the conversion of angiotensinogen to angiotensin I.
Many drugs control blood pressure by interfering with angiotensin or aldosterone. However, when these drugs are used chronically, the body increases renin production, which drives blood pressure up again. Therefore, doctors have been looking for a drug to inhibit renin directly. Aliskiren is the first drug to do so.[7][8]
Aliskiren may have renoprotective effects that are independent of its blood pressure−lowering effect in patients with hypertension, type 2 diabetes, and nephropathy who are receiving the recommended renoprotective treatment. According to the AVOID study, researchers found that treatment with 300 mg of aliskiren daily, as compared with placebo, reduced the mean urinary albumin-to-creatinine ratio by 20% (95% confidence interval, 9 to 30; P<0.001), with a reduction of 50% or more in 24.7% of the patients who received aliskiren as compared with 12.5% of those who received placebo (P<0.001). Furthermore, the AVOID trial shows that treatment with 300 mg of aliskiren daily reduces albuminuria in patients with hypertension, type 2 diabetes, and proteinuria who are receiving the recommended maximal renoprotective treatment with losartan and optimal antihypertensive therapy. Therefore, direct renin inhibition will have a critical role in strategic renoprotective pharmacotherapy, in conjunction with dual blockade of the renin−angiotensin−aldosterone system with the use of ACE inhibitors and angiotensin II–receptor blockers, very high doses of angiotensin II−receptor blockers, and aldosterone blockade.[9]
Rarely: allergic swelling of the face, lips or tongue and difficulty breathing
Contraindications
Pregnancy: other drugs such as ACE inhibitors, also acting on the renin-angiotensin system have been associated with fetal malformations and neonatal death[10]
Breast feeding: during animal studies, the drug has been found present in milk.[10]
Aliskiren has not yet been evaluated in patients with significantly impaired renal function.
Drug interactions
Aliskiren is a minor substrate of CYP3A4 and, more important, P-glycoprotein:
Atorvastatin may increase blood concentration, however no dose adjustment needed.
Possible interaction with ciclosporin (the concomitant use of ciclosporin and aliskiren is contraindicated).
Caution should be exercised when aliskiren is administered with ketoconazole or other moderate P-gp inhibitors (itraconazole, clarithromycin, telithromycin, erythromycin, amiodarone).
Doctors should stop prescribing aliskiren-containing medicines to patients with diabetes (type 1 or type 2) or with moderate to severe kidney impairment who are also taking an ACE inhibitor or ARB, and should consider alternative antihypertensive treatment as necessary.[11]
References
^ Gradman A, Schmieder R, Lins R, Nussberger J, Chiang Y, Bedigian M (2005). “Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients”. Circulation111 (8): 1012–8. doi:10.1161/01.CIR.0000156466.02908.ED. PMID15723979.
^ Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK. “Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy,” N Engl J Med 2008;358:2433-46.
When myocardial infarction (MI) is complicated by cardiogenic shock, use of intraaortic balloon counterpulsation (IABP) did not reduce mortality among patients scheduled for revascularization–a finding that calls into question current guidelines for treating cardiogenic shock in this population.
SHOCK II: IABP Use Questioned
By Peggy Peck, Editor-in-Chief, MedPage Today
Published: August 27, 2012
When myocardial infarction (MI) is complicated by cardiogenic shock, use of intraaortic balloon counterpulsation (IABP) did not reduce mortality among patients scheduled for revascularization, a finding that calls into question current guidelines for treating cardiogenic shock in this population.
Note that authors of an editorial wrote that data from IABP-SHOCK II, and a number of recent meta-analyses, “do not support the routine use of IABP in patients with acute myocardial infarction complicated by cardiogenic shock, and the level I guideline recommendation is now strongly challenged.”
When myocardial infarction (MI) is complicated by cardiogenic shock, use of intraaortic balloon counterpulsation (IABP) did not reduce mortality among patients scheduled for revascularization — a finding that calls into question current guidelines for treating cardiogenic shock in this population.
At 30 days, only 60% of the patients treated with IABP were still alive, a mortality that was no different from the rate in the control group (39.7% versus 41.3% relative risk 0.96, 95% CI 0.79-1.17, P=0.69), according to findings from the IABP-SHOCK II trial reported online by the New England Journal of Medicine.
The findings were simultaneously reported as a Hot Line presentation at the European Society of Cardiology meeting in Munich.
Holger Thiele, MD, from University of Leipzig-Heart Center, Leipzig, Germany, and colleagues recruited 600 patients for a randomized, prospective, open-label, multicenter trial and assigned 300 to IABP.
While there was no mortality benefit for IABP, there also was no apparent harm:
Rates of major bleeding: 3.3% versus 4.4% in controls (P=0.53)
Rates of sepsis: 15.7% versus 20.5% (P=0.15)
Rates of stroke: 0.7% versus 1.7% (P=0.28)
Rates of peripheral ischemic complications: 4.3% versus 3.4% (P=0.53)
Current American College of Cardiology/American Heart Association guidelines for treatment of STEMI support use of IABP in this population, but that recommendation comes from a trial “that did not address this question, it really looked at the question of revascularization of these patients,” said Mariell Jessup, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia.
The earlier trial, called SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock), “was really about bypass surgery in these patients,” she said.
Jessup, who is president-elect of the American Heart Association, told MedPage Today, that the results of the IABP-SHOCK II trial “may very well be the most important finding to be reported at this meeting.”
She said the current Class I recommendation is for use of IABP when the patient is not stable. “It is possible that this [IABP-SHOCK II] could completely change this guideline.”
Jessup noted that use of IABP has become the norm for treating these patients and she suggested that physicians will find it hard to resist using IABP because “it is hard for physicians to not do something for these patients.”
Christopher O’Connor, MD, and Joseph Rogers, MD, echoed Jessup’s view in an NEJM editorial. They are from Duke University in Durham, N.C.
Under the title, “Evidence for Overturning the Guidelines in Cardiogenic Shock” O’Connor and Rogers wrote that data from IABP-SHOCK II, and a number of recent meta-analyses, “do not support the routine use of IABP in patients with acute myocardial infarction complicated by cardiogenic shock, and the level I guideline recommendation is now strongly challenged. Members of guideline committees and clinicians should take note of another example of a recommendation that is based on insufficient data.”
Patients in the IAPB-SHOCK trial were recruited from June 16, 2009 through March 3, 2012 at 37 centers in Germany.
Thirty of the 299 patients assigned to the control group did eventually undergo IABP, usually within 24 hours of randomization, and 26 of those patients were classified as protocol violations. Likewise, 13 patients assigned to IABP did not undergo the treatment, with death being the most common reason.
The authors noted a number of limitations, starting with lack of blinding, and the failure to obtain “hemodynamic measurements or assess laboratory inflammatory markers other than blood pressure, heart rate, and C-reactive protein levels.”
Also, the mortality rate in both arms was lower than anticipated — 40% versus a range of 42% to 48% in other studies — suggesting that most patients in this study had mild or moderate cardiogenic shock, which could limit the generalizability of these results, they cautioned.
“Finally, we do no yet have any information about longer-term outcomes. Since a balloon intraaortic counterpulsation was used for a median of only 3 days, it seems unlikely that any beneficial effect will become evident later than 30 days,” they wrote.
The trial was supported by the German Research Foundation, the German Heart Foundation, the German Cardiac Society, Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte, the University of Leipzig-Heart Center, Marquet Cardiopulmonary, and Teleflex Medical.
Thiele disclosed financial support from Eli Lilly, Terumo, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, and the Medicines Company.
Primary source: New England Journal of Medicine
Source reference:
Thiele H, et al. “Intraaortic balloon support for myocardial infarction with cardiogenic shock” N Engl J Med 2012; DOI: 10.1056/NEJMoal208410.
Additional source: New England Journal of Medicine
Source reference:
O’Connor CM, Rogers JG. “Evidence for overturning the guidelines in cardiogenic shock” N Engl J Med 2012; DOI: 10.1056/NEJMel209601.
It is generally agreed by radiologists and oncologists that in order to provide a comprehensive work-flow that complies with the principles of personalized medicine, future cancer patients’ management will heavily rely on “smart imaging” applications. These could be accompanied by highly sensitive and specific bio-markers, which are expected to be delivered by pharmaceutical companies in the upcoming decade. In the context of this post, smart imaging refers to imaging systems that are enhanced with tissue characterization and computerized image interpretation applications. It is expected that such systems will enable gathering of comprehensive clinical information on cancer tumors, such as location, size and rate of growth.
What is the main incentive for promoting cancer patients’ management based on smart imaging?
It promises to enable personalized cancer patient management by providing the medical practitioner with a non-invasive and non-destructive tool to detect, stage and follow up cancer tumors in a standardized and reproducible manner. Furthermore, applying smart imaging that provides valuable disease-related information throughout the management pathway of cancer patient will eventually result in reducing the growing burden of health-care costs related to cancer patients’ treatment.
Let’s briefly review the segments that are common to all cancer patients’ pathway: screening, treatment and costs.
Screening for cancer:It is well known that one of the important factors in cancer treatment success is the specific disease staging. Often this is dependent on when the patient is diagnosed as a cancer patient. In order to detect cancer as early as possible, i.e. before any symptoms appear, leaders in cancer patients’ management came up with the idea of screening. To date, two screening programs are the most spoken of: the “officially approved and budgeted” breast cancer screening; and the unofficial, but still extremely costly, prostate cancer screening. After 20 years of practice, both are causing serious controversies:
In trend analysis of WHO mortality data base [1], the authors, Autier P, Boniol M, Gavin A and Vatten LJ, argue that breast cancer mortality in neighboring European countries with different levels of screening but similar access to treatment is the same: “The contrast between the time differences in implementation of mammography screening and the similarity in reductions in mortality between the country pairs suggest that screening did not play a direct part in the reductions in breast cancer mortality”.
In prostate cancer mortality at 11 years of follow-up [2], the authors,Schröder FH et. al. argue regarding prostate cancer patients’ overdiagnosis and overtreatment: “To prevent one death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected”.
The lobbying campaign (see picture below) that AdmeTech (http://www.admetech.org/) is conducting in order to raise the USA administration’s awareness and get funding to improve prostate cancer treatment is a tribute to patients’ and practitioners’ frustration.
Treatment: Current state of the art in oncology is characterized by a shift in the decision-making process from an evidence-based guidelines approach toward personalized medicine. Information gathered from large clinical trials with regard to individual biological cancer characteristics leads to a more comprehensive understanding of cancer.
Quoting from the National cancer institute (http://www.cancer.gov/) website: “Advances accrued over the past decade of cancer research have fundamentally changed the conversations that Americans can have about cancer. Although many still think of a single disease affecting different parts of the body, research tells us through new tools and technologies, massive computing power, and new insights from other fields that cancer is, in fact, a collection of many diseases whose ultimate number, causes, and treatment represent a challenging biomedical puzzle. Yet cancer’s complexity also provides a range of opportunities to confront its many incarnations”.
Personalized medicine, whether it uses cytostatics, hormones, growth inhibitors, monoclonal antibodies, and loco-regional medical devices, proves more efficient, less toxic, less expensive, and creates new opportunities for cancer patients and health care providers, including the medical industry.
To date, at least 50 types of systemic oncological treatments can be offered with much more quality and efficiency through patient selection and treatment outcome prediction.
Figure taken from presentation given by Prof. Jaak Janssens at the INTERVENTIONAL ONCOLOGY SOCIETY meeting held in Brussels in October 2011
For oncologists, recent technological developments in medical imaging-guided tissue acquisition technology (biopsy) create opportunities to provide representative fresh biological materials in a large enough quantity for all kinds of diagnostic tests.
Health-care economics: We are living in an era where life expectancy is increasing while national treasuries are over their limits in supporting health care costs. In the USA, of the nation’s 10 most expensive medical conditions, cancer has the highest cost per person. The total cost of treating cancer in the U.S. rose from about $95.5 billion in 2000 to $124.6 billion in 2010, the National Cancer Institute (www.camcer.gov) estimates. The true sum is probably higher as this estimate is based on average costs from 2001-2006, before many expensive treatments came out; quoting from www.usatoday.com : “new drugs often cost $100,000 or more a year. Patients are being put on them sooner in the course of their illness and for a longer time, sometimes for the rest of their lives.”
With such high costs at stake, solutions to reduce the overall cost of cancer patients’ management should be considered. My experience is that introducing smart imaging applications into routine use could contribute to significant savings in the overall cost of cancer patients’ management, by enabling personalized treatment choice and timely monitoring of tumors’ response to treatment.
Latest Medical Devices, Equipment, & Drug Information in Cardiology
Search the latest Cardiology developments in medical devices, equipment and approved drugs. Find new FDA approved procedures, drugs and devices in the MDLinx Product Center.
Dr. Joseph Loscalzo of BWH, the moderator of the Cardiology Panel — NEJM Dialogue in Medicine, June 22, 2012 has asked the Panel members: What are the new innovations to be foreseen by each member of the Panel which included Panelists:
Dr. Craig Smith of Columbia University Medical Center bet the future of cardiovascular medical devices on the Implantable Synchronized Cardiac Assist Device which has three version, Left ventricle, Right Ventricle or both
Dr. Eugene Braunwald, Founding Chairman, TIMI Study Group(TIMI stands for ‘Thrombolysis In Myocardial Infarction’ and is the name of an Academic Research Organization (ARO) that, since it was founded by Dr. Eugene Braunwald in 1984, has conducted numerous practice-changing clinical trials in patients with cardiovascular disease or risk factors for cardiovascular disease, he has expressed anticipation of the next big and much needed to be available — the Multiple Pill, one drug that is a combination drugs of ASA, TZD, BB, ACE, Statin.
On this Scientific Web Site — Frontiers in Cardiology is one of the Research Categories on Cardiovascular disease, research directed by Dr. Aviva Lev-Ari, noted to be of great relevance to the innovations foreseen by Dr. Craig Smith and by Dr. Brounwald, as expressed by them on June 22, 2012 in Boston, MA
To read on the only currently available Multiple Pill — go to
Lev-Ari, A. (2012b). Triple Antihypertensive Combination Therapy Significantly Lowers Blood Pressure in Hard-to-Treat Patients with Hypertension and Diabetes
Fifty years ago, when the curator of the Boston Medical Library, Henry Viets, collated a score of the most important articles that had been published in the first century and a half of the New England Journal of Medicine, 10 of the 20 related to neurologic conditions. Viets HR. A score of significant papers published in the Journal during the last hundred and fifty years. N Engl J Med 1962;266:23-28
On the occasion of its 200th anniversary, one might ask why so many articles on neurologic and psychiatric diseases have been published in the Journal and what impact these pieces have had on their respective fields. Although the Journal is replete with reports of neurologic conditions that have entered the canon of medicine, it has been the large number and the breadth of clinical trials that have redefined neurology and psychiatry as active, therapeutic specialties. This article reviews the evolution of our understanding of neurologic and psychiatric conditions during the past two centuries.
Modern scientific neurology, based on neuropathology and neurophysiology, began after World War II. By 1952, patients with tabes dorsalis and general paresis had practically disappeared from hospital wards. Antimicrobial agents had changed the course of bacterial and tuberculous meningitis, but poliomyelitis was still a nemesis. Denny-Brown‘s Shattuck Lecture on the state of neurology that year in the Journal pronounced that, freed from its preoccupation with syphilology and now separating itself from internal medicine and psychiatry, neurology had “entered on an extremely productive and virile phase.” Denny-Brown DE. The changing pattern of neurologic medicine. N Engl J Med1952;246:839-846
Denny-Brown emphasized recent contributions on the neurologic aspects of liver failure, the recognition that transient ischemic attacks were due to occlusion of the carotid artery, and the emerging understanding of increased intracranial pressure. There was little question at the time that neurologic and psychiatric diseases both acted on the same brain, but Denny-Brown’s position in his Shattuck Lecture marked the emergence of American neurology, pointedly disengaging it from the popular practice of neuropsychiatry and aligning it with internal medicine. He provided a modern manifesto for neurology, which nonetheless remained largely an elegant diagnostic specialty.
TWO INFLUENTIAL ARTICLES
A seemingly mundane clinical neurology article in the pages of the Journal had a highly felicitous effect on the relief of human suffering by addressing the problem of sciatica. That 1934 report by Mixter and Barr
Mixter WJ, Barr JS. Rupture of the intervertebral disc with involvement of the spinal canal. N Engl J Med 1934;211:210-215 established intervertebral disk rupture with nerve-root compression as the mechanism and also provided a remarkably sophisticated analysis of cervical-disk herniation and cord compression. It presented detailed instructions for the cure — in both instances, laminectomy. Twelve terse pages provided meticulous clinical descriptions and drawings of the corrective operation (Figure 1FIGURE 1Mixter and Barr’s Descriptions and Operation for Disk Rupture.). The enduring impact of that article, as well as the continuity of attention to this topic in the Journal, was affirmed by a 2007 report on a clinical trial that showed the superiority of surgery over conservative management. Peul WC, van Houwelingen HC, van den Hout WB, et al. Surgery versus prolonged conservative treatment for sciatica. N Engl J Med 2007;356:2245-2256
The excess of ill-advised laminectomies for back pain that followed Mixter and Barr’s article was not their doing; in a less frequently cited but more detailed contribution published in the Journal 6 years after their first report, they state, “We wish to emphasize at this point that a large proportion of the cases of sciatica resolve spontaneously or under conservative orthopedic treatment.” Mixter WJ, Barr JS. Protrusion of the lower lumbar intervertebral disks. N Engl J Med1940;223:523-529
Second article, An influential article in psychiatry from the New England Journal of Medicine with vast secular influence was “Neurasthenia, or Nervous Exhaustion” by George Beard, published in 1869. Beard G. Neurasthenia, or nervous exhaustion. Boston Med Surg J 1869;80:217-221
He spoke of “a condition of the system that is, perhaps, more frequently than any other in our time at least, the cause and effect of disease. . . . Both anemia and neurasthenia are most frequently met with in civilized intellectual communities. They are part of the compensation for our progress and refinement.” Beard G. Neurasthenia, or nervous exhaustion. Boston Med Surg J 1869;80:217-221
The use of the label “neurasthenia,” and probably its reported incidence, expanded greatly after Beard’s article appeared. It was called the “American disease” by the illustrious French neurologist, J.-M. Charcot, who took it up for study as a strictly neurologic condition. By medicalizing the misfortunes of life, for which care is still so frequently sought, physicians became comfortable invoking a patient’s constitutional makeup, as if it were a physical entity, as the substrate for exhaustion, melancholia, depression, discouragement, weakness, and headache.
THE RISE OF BIOLOGIC PSYCHIATRY
Some topics in every field turn out to be fraught with specious ideas, and neurology and psychiatry have grappled with many of them. We cannot know whether the absence of articles on phrenology in BMSJ was an implicit message or whether it was a reflection of Boston’s medical orthodoxy. Many positive reports of magnetism applied to nervous conditions and endorsements of autointoxication as the cause of mental diseases were, however, published in the Journal. Briggs LV. A consideration of auto-intoxication and auto-infection as cause of various mental disorders. Boston Med Surg J 1905;152:1-5, 36
Most of these quaint notions simply reflected the medical ideologies of the time. For an example of early continuity of subject matter regarding the nerves that has appeared in the Journal one has only to look at Brown-Séquard’s work on electrical activity of the nervous system and J.C. Warren’s derisive article “Animal Magnetism,” stating that the concept, “which some thirty years ago excited great attention . . . has since been viewed as one of the remarkable impositions on the credulity of mankind.” Warren JC. Animal magnetism. Boston Med Surg J 1814;3:40-46
But the use of electricity for brain disorders is now again invoked through the technology of deep-brain stimulation. Escaping from the stigma of psychosurgery, articles in the Journal have expanded the application of deep-brain stimulation well beyond its usual use in Parkinson’s disease and found substantiation for its use in intractable obsessive–compulsive disorder. Mallet L, Polosan M, Jaafari N, et al. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med 2008;359:2121-2134[Erratum, N Engl J Med 2009;361:1027.] and in dystonia. Kupsch A, Benecke R, Muller J, et al. Pallidal deep-brain stimulation in primary generalized or segmental dystonia. N Engl J Med 2006;355:1978-1990 and Vidailhet M, Vercueil L, Houeto JL, et al. Bilateral deep brain stimulation of the globus pallidus in primary generalized dystonia. N Engl J Med 2005;352:459-467
When psychodynamic systems that attributed mental diseases to unconscious conflicts were popularized in the mid-20th century, there was a conspicuous absence of articles about them in theJournal. The exception was psychosomatic medicine. In a 1948 article in the Journal, A.O. Ludwig wrote that “emotional influences acting over longer or shorter periods result at first in disturbed physiology and eventually in structural change. Peptic ulcer is the simplest example . . . [u]lcerative colitis . . . asthma, hay fever and urticaria, certain skin diseases, such as eczema and neurodermatitis, migraine, possibly certain cases of epilepsy; hypertension and rheumatoid arthritis.” Ludwig AO. The practical importance of modern concepts of psychosomatic relations. N Engl J Med 1948;238:175-178. Concerning much of 20th-century psychiatry, including psychoanalysis, however, the Journal spoke through its silence. With the ascent of biologic psychiatry in the first decade of the 21st century, large pragmatic “efficacy” trials identified by their acronyms have appeared in the pages of the Journal — for depression (STAR*D), Trivedi MH, Fava M, Wisniewski SR, et al. Medication augmentation after the failure of SSRIs for depression. N Engl J Med 2006;354:1243-1252 psychosis (CATIE), Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005;353:1209-1223[Erratum, N Engl J Med 2010;363:1092-3.] and dementia (CATIE-AD). Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med 2006;355:1525-1538
These studies affirm the value but expose the shortcomings and risks of medical treatment for mental conditions and suggest that the field may have moved a bit too far, as in a quip by the late Leon Eisenberg, from “brainlessness to mindlessness.” Eisenberg L. Mindlessness and brainlessness in psychiatry. Br J Psychiatry 1986;148:497-508
These articles about psychiatry published in the Journal are influencing that field, as other articles have in neurology and neurosurgery, bringing the study of mental life and its diseases back into contemporary medicine and thereby rejoining the specialties of the brain.
For 200 years, the Journal has seen neurology and psychiatry evolve from a European to an international scope, from an emphasis on diagnosis to an emphasis on treatment, and has published many of the fundamental descriptions of nervous and mental diseases while cultivating a new and potent therapeutic course. One would expect the next 100 years to bring a new outlook on diseases of the nervous system that is based on fundamental biology, but the need for keen observation of the individual patient is not likely to be supplanted.
With this issue, the New England Journal of Medicine marks its 200th anniversary. In January 1812, as the first issue came off the handset letterpress, few of its founders could have predicted such continuity and success. (See Figure 1FIGURE 1Illustration from “Cases of Organic Diseases of the Heart and Lungs,” by John C. Warren, April 1, 1812, Issue of the Journal., from an 1812 issue.) John Collins Warren, the renowned Boston surgeon, his colleague James Jackson, a founder of Massachusetts General Hospital, and the small group of distinguished colleagues who joined them in starting the New England Journal of Medicine and Surgery, and the Collateral Branches of Science expressed modest and largely local aspirations for the enterprise. Boston, a growing urban center, and the wider New England environs had no medical journal of their own, although much medical knowledge and practice was considered region-specific. Although the name and format of the Journal would vary until 1928, 7 years after its ownership passed to the Massachusetts Medical Society, it remains the longest continuously published medical periodical in the world. The prospectus for the Journal, a call for papers issued in late 1811, explained the goals of Warren and his collaborators: “The editors have been encouraged to attempt this publication by the opinion, that a taste for medical literature has greatly increased in New England within a few years past. New methods of practice, good old ones which are not sufficiently known, and occasional investigations of the modes in common use, when thus distributed among our medical brethren in the country, will promote a disposition for inquiry and reflection, which cannot fail to produce the most happy results.”1
At a time of intense debate and controversy regarding the causes of disease, the nature of therapeutics, and the basis of professional authority, the young Journal worked to steer a middle course. This was certainly advisable from a commercial point of view, since it could easily alienate diverse medical readers by endorsing a particular therapeutic system or theory. But this approach also established the ecumenical temper of theJournal, which based its early publications on a commitment to empirical observation and an outlook skeptical of conventional medical wisdoms. As the editors explained in 1837, “It has been a point of ambition with us . . . to make these pages the vehicle of useful intelligence, rather than the field of warfare. . . . The Journal is to all intents and purposes, designed to be a record of medical and surgical facts. It is the medium through which the profession may interchange sentiments and publish the results of their experience” (see Historical Journal Articles Cited).
The observation and investigation of disease is perhaps the most salient consistent feature of theJournal. From the meticulous description of angina pectoris in the first issue to the early descriptions of AIDS in the early 1980s, there has been an ongoing recognition that therapeutic approaches must await the sharp articulation of symptoms. The first decades of the Journal‘s history reflected the intensive concern with the epidemics affecting New England and the new nation, and it was not unusual during the early years for authors to direct attention to the environment as a critical variable in the production of disease. John Gorham, an editor writing in 1828, offered a “Medical Report of the Weather and Prevalent diseases for the last Three months.” Such articles may appear both quaint and humorous from our contemporary scientific perch, but they reveal a serious commitment to understanding more fully the vagaries of epidemic disease that could devastate town and country in short order. Furthermore, they offer a complex notion of causality that characterized much 19th-century medicine, in which disease was seen as the result of interactions of the patient’s individual “constitution” with an ever-changing and often dangerous environment.2 By the late 20th century, many observers would renew concerns voiced more than a century earlier about the environment’s relationship to disease.
The Journal provides a powerful record of the course taken by medical science and its applications over a 200-year period. It quickly became a conduit for reporting new investigations and findings and for summarizing and disseminating evolving medical knowledge across the widest range of practice. After issuing favorable reports on bloodletting, herbal treatments, and other “heroic” practices of the early 19th century, the Journal began to reflect a growing skepticism toward such approaches. Authors increasingly pointed to the benefits of the healing powers of nature — vis medicatrix naturae — as physicians came to recognize some of the iatrogenic effects of their interventions that had previously been difficult to differentiate from the course of serious disease.3Therapeutics based on ancient notions of humoral excess and depletion gave way to a renewed emphasis on empirical observation and experiment. The first demonstration of surgical anesthesia, conducted at Massachusetts General Hospital in 1846 in an amphitheater soon to be renamed the “Ether Dome,” was first reported in the Journal (Figure 2FIGURE 2“First Operation under Ether,” 1846, with Related Journal Report.). Others quickly began using ether in their practices. One surgeon wrote in the Journal, “I performed the amputation of an arm, the second under the use of ether, while the patient was dreaming of her harvest labors in Ireland, and felt grating but not painful sensations, `as if a reaping-hook was in her arm’” (1850).
EDUCATION AND THE DISSEMINATION OF MEDICAL KNOWLEDGE
From the beginning, the Journal has critically covered essential debates about the character and quality of medical education. The editors considered one of their primary goals to be educating the profession, so assessment of medical school programs was in harmony with their mission; after all, these schools produced their readers. In the late 19th century, the Journal frequently noted the great inconsistencies in educational standards and quality. A decade before the publication of the Flexner reforms, prominent Boston physician Henry Bowditch anticipated many key aspects of the report when he called for linking medical education to universities, lengthening the course of study, and demanding deeper preparation in the sciences and wider domains of knowledge (1900). He argued for active learning to replace didactics, a theme that would echo through the debates about medical education. As late as 1900, when Bowditch proposed his reforms in the Journal, less than half the students at Harvard Medical School had completed a college education. After the publication of the Flexner Report in 1910 and the massive changes that followed, the Journalapplauded the consolidation of medical education on a new scientific foundation.
TOO MUCH TO KNOW
With the radical expansion and shifting of the scientific basis of medicine at the turn of the 20th century, the Journal recorded growing interest in and concern about specialization. From a largely undifferentiated notion of medical training and expertise, many new and specific divisions of the medical profession developed.6 Whereas the Journal came to view specialization as the inevitable result of exploding medical knowledge, the creation of medical “specializm” was viewed with considerable skepticism and lamentation, if not outright hostility. Much ink was spilled in attempts to determine the relationship of general knowledge and practice to increasingly specific (and limited) areas of expertise. How would the “whole patient” be treated when specialties had divided the body into organ systems and medicine into categories of disease and authority over various technologies and techniques?
THE PERMEABLE BOUNDARIES OF SCIENCE AND MEDICINE
Despite the Journal‘s deep commitment to empirical reasoning and scientific rationality, cultural and political beliefs and values are ever apparent in its pages. In some instances, professional prerogatives and social assumptions are exposed. For example, when the introduction of women students at Harvard Medical School was debated in 1878, the Journal expressed concern: “It would . . . be impossible to avoid an indiscriminate mingling of the sexes in the dissecting or autopsy rooms, and in the amphitheatres, to witness exercises which justly have hitherto been thought of a character to be witnessed by one sex alone.” Harvard would ultimately admit women in 1945, when the war caused a shortage of male candidates. In the 1950s, the Journal expressed regret that some women physicians with children “have found it impossible to carry on their practices” (1954).
REFLECTIONS ON THE JOURNAL AT 200
While the Journal embraced new science and the critical apparatus of peer review, it rejected a narrow notion of specialism, continuing to cover the widest range of contributions to medical knowledge. In an increasingly atomized medical world, the commitment to publish on cross-cutting educational, professional, ethical, and policy issues pulled together diverse readers, including physicians and other health care providers, public health experts, and policymakers, around issues that were often beyond their immediate expertise. The radical growth of teaching hospitals, federal funding for basic science and clinical research, and academic medical centers (all developments reflected in the Journal) have been crucially linked to the Journal‘s growth, stability, and success.
During the Journal’s first 200 years of publication, medicine and health care moved from the social periphery to become dominant aspects of our science, culture, and economy. The Journalunquestionably owes its success and stability to this monumental shift in the status, authority, and impact of biomedicine. But the Journal has also played a critical role in these developments. By combining a commitment to publishing papers of scrupulous scientific merit across wide-ranging domains, with a recognition of the central questions and values uniting the profession, the Journalhas remained true to its founders’ vision. It has recognized that advances in medical science can finally be assessed only in the context of delivery, care, and outcome. The Journal reflects today, as at its inception, a view that medical science and its applications are fundamentally tied to patient care and public health. It therefore continues to draw a range of readers wider than Warren could have imagined. Today, the ability to disseminate publications so widely through digital technologies promises to bring innovations in medical knowledge to a new set of global constituents. The first hundred issues of Warren’s journal were, of course, distributed on horseback.
HISTORICAL JOURNAL ARTICLES CITED.
New England Journal of Medicine and Surgery, and the Collateral Branches of Science
We are publishing a series of engaging Review and Perspective articles from established authors who are preeminent in their fields. Each article explores a story of progress in medicine over the past 200 years. These articles will appear every other week during 2012 and be collected here. Check the News & Eventssection of this site for announcements about upcoming articles.
Zithromax (azithromycin), is not only a more expensive antibiotic than other antibiotics but also seems to be an expensive one at Heart. Doctors should weigh other options for people already prone to heart problems, the researchers and other experts suggested. It is a popular antibiotic because it often can be taken for a fewer days compared to other antibiotics, for example: about 10 days for amoxicillin and other antibiotics and five-day course will suffice in case of Zithromax.
Azithromycin (Photo credit: Wikipedia)
It is widely used for bronchitis, sinus infections and pneumonia, and other common infections but seems to increase chances for sudden deadly heart problems. A rare but surprising risk found in a 14-year study. Also, antibiotics in the same class as Zithromax have been linked with sudden cardiac death. In the current study, patients those on Zithromax were about as healthy as those on other antibiotics, making it unlikely that an underlying condition might explain the increased death risk, researchers said.
Researchers analysis at Vanderbilt University indicates that there were 29 heart-related deaths among those who took Zithromax during five days of treatment. Their risk of death while taking the drug was more than double that of patients on another antibiotic, amoxicillin, or those who took none.
To compare risks, the researchers calculated that the number of deaths per 1 million courses of antibiotics would be about 85 among Zithromax patients versus 32 among amoxicillin patients and 30 among those on no antibiotics. The highest risks were in Zithromax patients with existing heart problems. Patients in each group started out with comparable risks for heart trouble, the researchers said. The results suggest there would be 47 extra heart-related deaths per 1 million courses of treatment with Zithromax. The risk of cardiovascular death was significantly greater with azithromycin than with ciprofloxacin but did not differ significantly from that with levofloxacin.
Dr. Harlan Krumholz, a Yale University health outcomes specialist who was not involved in the study said that “People need to recognize that the overall risk is low,”. More research is needed to confirm the findings, but still, he said patients with heart disease “should probably be steered away” from Zithromax for now.
At the same time, Dr. Bruce Psaty, a professor of medicine at the University of Washington, of opinion that doctors and patients need to know about the potential risks. He said the results also raise concerns about long-term use of Zithromax, which other research suggests could benefit people with severe lung disease. Additional research is needed to determine if that kind of use could be dangerous, he said.
Pfizer is committed to patients safety and issued a statement saying it would thoroughly review the study and “Patient safety is of the utmost importance to Pfizer and we continuously monitor the safety and efficacy of our products to ensure that the benefits and risks are accurately described,” the company said.
2012pharmaceutical
sjwilliamspa