Gardasil: New Vaccine that Prevents Cervical Cancer

(HPV Vaccine , Joan Stephenson, PhD , JAMA. June 2007;297:2578)

Q. Can Cervical Cancer be prevented ?

• Cervical Cancer is commonly caused by HPV strains 16 and 18
• A new vaccine "Gardasil" manufactured by Merck Pharma prevents infection by these strains hence deemed useful in preventing cervical cancer
• The vaccine is not effective in preventing cancer in women who are already infection by HPV, hence routine screeing for Cervical cancer cannot be substituted.

New Guidelines for Hemorraghic Stroke.

(Hemorrhagic Stroke Guidelines Issued , Mike Mitka , JAMA. June 2007;297:2573-2575. )


Q. Which new drug is said to bring a revolution in management of Hemorraghic stroke ?

Recombinant Activated Factor VII (NovoSeven- Novo Nordisk) – this drug reduces the bleeding and hence is likely to reduce the growth of hematoma. Trials are on for this and is increasingly used in advance setups for Hemorraghic stroke. This drug is likely to bring a revolution in management of Hemorraghic stroke.


Q. When is CT Scan Better than MRI and MRI Better than CT in Diagnosis of Hemorraghic Stroke ?

CT better than MRI

• Show associated extension of stroke into the ventricles
• In patients who are unconscious, vomiting or on ventilator
  
  MRI better than CT
• Detecting Underlying Structural lesions
• Small Prior hemorrhages

Important CLASS I and CLASS II Recomedations of the Guidelines

The guidelines' class I recommendations (based on evidence for and/or general agreement that the intervention is useful and effective) specify always treating seizures in patients with hemorrhagic stroke with appropriate antiepileptic therapy and treating fever.

The document's class II recommendations (for which evidence of the intervention's usefulness/efficacy is less well established and is based on conflicting evidence and/or a divergence of opinion) include
¬ using a balanced and graded approach to treating elevated cranial pressure,
¬ starting with head-of-the-bed elevation,
¬ analgesia,
¬ and sedation;
¬ treating hyperglycemia;
¬ treating hypertension to target blood pressure levels using a variety of medications including Nicardipine;
¬ and treatment with recombinant activated factor VII within the first 3 to 4 hours after onset, but only in a clinical trial setting, as efficacy and safety must still be confirmed.

Q. What is the Role of Surgery in Acute Hemorraghic Stroke ?

The Role of Surgery in Hemorraghic Stroke is Controversial. The 2007 STICH Guidelines (International Surgical Trial in Intracerebral Hemorrhage ) recommendations are included in the current guidelines which are.

Absolute Indication for Surgery (Class I)

• Hemorrhage > 3cm
• Detoriating Neurologically
• Brain Stem Compression
• Hydrocephalus from Ventricular compression
  
  Relative Indication (Class II)
• Surgeons should consider evacuating lobar clots 1 cm from head surface by standard craniotomy
  
  Q. What is Ultra early Craniotomy and what is its role in Management of Hemorraghic stroke ?
  ¬ Ultra Early craniotomy is performing a surgery within 12 hrs of onset of stroke.
  ¬ This is found to have no clear evidence of benefit to moratlity in the guideline
  ¬ Infact on the other hand it may increase the risk of recurrent rebleeding

Q. What is Endocsopic Aspiration and what is its role ?

¬ Another intervention of interest involves endoscopic aspiration. It means placing catheters into the clot and sucking it out more gently and without going through too much brain
¬ There has been some positive glimmering, but nothing definitive according to the guidelines
¬ The new guidelines give endoscopic aspiration a class II recommendation, based on a small, single-center randomized trial of 100 patients.
¬ That study found patients whose clots (at least 10 mL in volume) were removed had better outcomes than those treated with medicine only (Auer LM et al. J Neurosurg. 1989;70:530-535).
¬ Endoscopic aspiration of smaller clots led to significantly better quality of life, but survival was similar to those in the medical group
¬ benefit was mostly limited to patients with lobar hematomas and those younger than 60 years.


Q. What are the Guidelines on End of Life Care in such patients ?

¬ But the guidelines advise treating such patients aggressively in the first 24 hours to see what happens, and then to make end-of-life decisions.
¬ This allows time for the physician, family, and patient to think about what is happening.

Management of Early Rheumatoid Arthritis

(Management of Early Rheumatoid Arthritis: E Suresh, Journal of the Association of Physicians of India JAPI, Volume 55, May 2007)

Q. What has been the ideological shift in management of Early Rhematoid Arthritis ?

In the earlier time the philosophy was “Go Slow, Go low” which means drugs were added in a pyramidal system, NSAIDS followed by DMARDS followed by Steroids. Now the idea is to start treating Rheumatoid Arthritis aggressively by starting DMARDs early. This is because it has been found that irreversible damage occurs to the joints once the window of opportunity in treatment in early Rheumatoid arthritis is lost when the inflammation is still active.

Q. What is the role of Cyclic Citrullinated Peptide (CCP) in early diagnosis of RA ?

CCP is an early marker of RA. Its prevalence in blood precedes symptoms of RA by years !

Q. How will you manage a patient with Early Undifferentiated Inflammatory Arthritis ?

Since the American Rheumatology Guidelines suggest that the symptoms must persist for 12 wk for diagnosis of RA, hence we cannot accurately diagnose a person to have Rheumatoid arthritis before that period passes. And yet like mentioned before, the window of opportunity presents early, hence to resolve this conflict trials are underway to Stop RA Very Early or SAVE trial.

According to the article if a patient presents with Rheumatoid like Polyarthritis early :

If multiple joints are involved give 120 mg of Methyl Prednisolone deep IM
If fewer joints are involved Intrarticular steroids are useful.

If Remission is not achieved for 12 wks patient is classified as having RA and started on DMARDs.

Q. Which are the best DMARDs to start with ?

Methotrexate, Sulphasalazine and Leflunomide are suggested as first line agents for monotherapy by the article.

Practical Pearl : Patients on Methotrexate should be discouraged to take alcohol.

Q. Are DMARDs safe in Pregnency ?

Methotrexate and Leflunomaide are proven teratogens. They are absolutely contraindicated in pregnancy. Patients should be off methotrexate for 3 months before they conceive. Cholestyramine or activated charcoal should be used for patients on Leflunomide to wash it off .

Sulphasalazine is relatively safe in pregnancy, though higher dose of folic acid should be prescribed.

Q. What is DAS score ?

DAS score or Disease activity score is an important parameter for monitoring prognosis of patients of RA. (See http://www.dasscore.nl/ for details. )

Score >5.1 suggests high disease activity

Q. What is the role of Infliximab ?

Infliximab is an Anti-TNF agent. It has been proven to be effective in RA. If given it is combined with Methotrexate. It gives remission of upto one year on stopping therapy. The article suggests that currently the use of Infliximab is limited to research settings due to its high cost.


Important Notice: It has been proven that COX-2 inhibitors (Coxibs) increase risk of MI, Stroke and Thrombosis

Q. What is most important contraindicated to intrarticular steroid injection ?

Septic Arthritis is an important C/I to Intraarticular steroid injection.

While injecting IA steroids care should be taken not to inject > 3 joints in one sitting and same joint not more than 3-4 times a year.

Q. Does Alternative medicine help in RA ?

Gamma linoleic acid, an important component of Ayurvedic drugs for RA is found useful in RA. Mediterranean diet, Vegetarian diet , Fish oil supplementation and Yoga are other alternative therapies found useful.

Q. What is the most important cause of death in patients with RA ?

Accelerated Atherosclerosis.

Low Molecular Weight Heparin in Viper Bite

(Trial Of Low Molecular Weight Heparin in the Treatment of Viper Bites: Paul V, Pudoor A et al. Journal of the Association of Physicians of India JAPI, Volume 55, May 2007)

Q. Should Low Molecular Weight Heparin (LMWH) be used in Viper Snake Bites ?

Yes. Viper venom is hematotoxic and increase the bleeding tendency yet LMWH which also increase bleeding tendencies is used in Viper Snake bite ! This is because one of the biggest problems with Viper snake bite is that it causes DIC (Disseminated Intravascular Coagulation), LMWH prevents DIC. Hence it is logical to use Heparin in Viper Snake bites. A study done by Paul, Pudor et al published in May 2007 in JAPI proves this to be true. They found it LMWH reduces the mortality and morbidity in patients with Viper bites.

Q. What are the two leading cause of death in patient with Viper bite ?

Hypotension and Acute Renal Failure are the two leading causes of death in patient with Viper Bite, both of which can be caused by DIC.

Q. Where does LMWH act ?

LMWH acts on Factor Xa in coagulation cycle

Q. What are the advantages and Disdvantages of LMWH over Unfractionated Heparin ?

LMWH has less chances of severe bleeding episodes than unfractionated heparin. Also it has better absorption through subcutaneous route and has not effect on platelets.Also LMWH does cause Nitrous oxide (NO) release from the vascular endothelium which is the culprit in causing hypotension.

The biggest drawback of using LMWH in viper bite patient compared to UFH (other than the cost which is substantially high for LMWH) is that it doesn’t prevent microvascular thrombosis which is an important cause of Renal failure in such patients. This is what they found in the study. LMWH couldn’t prevent renal failure like UFH could.

Conclusion : It is a good Idea to Use Low Molecular Weight heparin in patients with Viper Snake Bite.

Philosophy of Medical Journal Review

Medical Journal form an essential part of medical teaching and learning. They are source of updates and the latest happening in almost every branch of medicine. But due to lack of time, motivation and increasing complexities of Medical journals, Undergraduate medical students, interns and Junior Resident doctors are not exposed to Medical Journals as they should be. Many of the latest information in medical journals is frequently asked during Viva in examination and many of MCQ in competitive exams are asked from research work published in medical journals.

Medical Journal Review is an attempt to expose the medical students to the world of Medical Journals. It provides the latest information , from the latest and most reputed medical journals around the world in a simple worded question answer format. It is invaluable for Undergraduates from IInd MBBS onwards who are preparing for their examination and also for those preparing for All India Entrance examination and other competitive exams like AIIMS, USMLE, PLAB etc.

Hope my effort enriches the knowledge of many students !

Regards,
Dr. Om Lakhani