April 1, 2008

Dear Doctor,

We are happy to present you the new volume of our Medical Newsletter in the monthof Bangla Naboborsho. In this issue, we have described a new crisis of today’s medicalprofession named antibiotic resistance. It has always been recognized that someorganisms will survive even in lethal doses of antibiotics due to adaptation andresistance and some will later become immune due to misuse or overuse resulting inrelapse of the infectious diseases. In Bangladesh, physicians often find it very difficultin treating infections, very often the patients had taken antibiotics without anyprofessional consultations and developed resistance to even the strongest antibiotics.This poses a great threat towards successful recovery from infectious diseases andpaves the way of spreading of the disease in the community. Such situation justifiesthe importance of ‘Rational Use of Antibiotics’- a well deserved concern for the healthcare professionals. Here, we have tried to emphasize the importance of the proper useof antibiotics and the necessity of developing a successful antibiotic policy.

In 1931, the French Medical Missionary Dr. Albert Schweitzer wrote, ‘Pain is a moreterrible lord of mankind than even death itself.’ Cancer pain is the most appropriate exampleof such saying. Today, this has become a serious public health issue and a challengefor those who have to deal with the individuals suffering from the physical and theemotional consequences of cancer pain. The article- ‘Controlling Cancer Pain’ highlightsabout the recent ongoing tools for assessing the cancer pain along with its remedy. Aspromised in our previous issue we have added the second topic of our trio-seriesabout ‘Arterial Aneurysm’ in vascular medicine.

Climate change is a significant and emerging global crisis threatening the existence ofhumankind. Our planet is suffering from the consequences of our irresponsibleactivities that have been going on for decades. Natural calamity like heat waves, floodand droughts, cyclones and tsunamis, and the emission of green house gases are slowlymaking our environment incompatible to survive for any living creature. Moreoverthese natural disasters are followed through with emergence of several fatal infectiousdiseases. As the health impact of changing climate is becoming unavoidable, we mustact right from this moment to save our earth. This year’s World Health Dayemphasizes the importance of halting this on-going devastating process by celebratingwith the campaign ‘Protecting Health from Climate Change’. We too as a part of thiscampaign present the article ‘Climate change and Human Health- Risks and Responses’ withthe aim of raising awareness in our society. In addition ‘Fact File’ has highlighteddiabetes as the disease is emerging as a global epidemic of today’s world. ‘Case Report’and ‘News from Internet’ are equipped with interesting features and ongoing clinical trialswith their outcomes.

With expectation of a very fortunate Bengali new year for all, we once again wish youShubho Naboborsho!

With best regards,

Prof. Farida HuqMBBS, M.Phil, FCPS, Ph.D.(London)Medical DirectorBeximco Pharmaceuticals Ltd.

Dr. Selina AkhtarSenior ManagerMedical DepartmentBeximco Pharmaceuticals Ltd.

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Antibiotics have been a tremendous successstory for over 50 years but this very successhas led to major problems with antibiotic

resistance. Bacterial resistance to antibiotics and thecritical need to curtail this global public heath problemhas created wide awareness among healthcareproviders, hospital administrators, public healthofficials, and even the common people of today'ssociety. Understanding and quantifying therelationship between antibiotic use and resistancerepresent an on-going quest and are critical, not onlyfor finding ways to reduce resistance, but also forimproving the quality of care in the treatment ofinfectious diseases. Such captious situation gave riseto the term 'Rational Use of Antibiotics' commonlyused now-a-days among the physician-scientistcommunity.

The Beginning of the Worry

Antibiotics have substantially reduced the threatposed by infectious diseases since their discoveryduring the 20th century. The use of these 'Wonderdrugs', over the years, have saved the lives and easedthe sufferings of millions. By bringing many seriousinfectious diseases under control, antibiotics have alsocontributed to the major gains in life expectancyexperienced during the latter part of the last century.But this medical miracle later on started to develop arather unexpected crisis, which is now widely knownas the term 'Resistance'.

In 1945-46, Professor Sir Alexander Fleming (theinventor of Penicillin) edited a book (Fleming, 1946a)in which he wrote an introductory chapter setting upsome general rules for penicillin treatment (Fleming1946b). There, he described that it should be used onlyfor the treatment of those infections caused bypenicillin-sensitive microbes. He also pointed out theimportance of acquired resistance even though therewas little of it at that time. But unfortunately, thiscomments remained sound and so was the guidelinedetailing its use (an appropriate route, adequatedosage for an appropriate period of time). It is seen bysome of the scientists of today that Fleming haddefined rational therapy in terms of the infection to betreated. Patients and the media may now be betterinformed, but irrational demand still continues.

Antibiotic Resistance: Consequences

The use of antibiotics has turned bacterial infectionsinto treatable conditions, rather than the lifethreatening scourges they once were. But today, theeffectiveness of many of these lifesavers is waning- aresult of the legacy of years of overuse and misuse.The gains are now seriously jeopardized by theemergence and spread of microbes that are resistant tocheap and effective first-line drugs. Health officials inthe United States are concerned that bacteria areturning into 'superbugs', resistant to more and moreantibiotics. Children, the elderly and those withweakened immune systems are particularly at risk.

The professional and lay literature continues to reportthe consequences of antibiotic misuse and the rise instrains resistant to antibiotics. When trying tounderstand drug resistance and develop ways tocontrol the mounting public health problem, there aremany factors to consider, which have both health andecological considerations. Organisms displaying amultiple drug resistance phenotype are becomingcommon in both nosocomial and community-acquiredinfections. Public health officials attribute thisalarming trend to the over-prescription and misuse ofantibiotics given to patients, and overuse of antibioticsin agriculture particularly the routine feeding of largevolumes of antibiotics to healthy livestock andpoultry.

The consequences of resistant development aresevere. Infections caused by resistant microbes fail torespond to treatment, resulting in prolonged illnessand greater risk of death. Treatment failures also leadto longer periods of infectivity, which increase thenumbers of infected people moving in the communityand thus expose the general population to the risk ofcontacting a resistant strain of infection. When

Rational Use of Antibiotics

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PUBLIC HEALTH

infections become resistant to first-line antimicrobials,treatment has to be switched to second- or third-linedrugs, which are nearly always much more expensiveand sometimes more toxic as well. An ideal exampleof such situation is the drugs needed to treatmultidrug-resistant tuberculosis. The most alarmingpart of such condition is that even if thepharmaceutical industry steps up efforts to developnew replacement drugs immediately, current trendssuggest that some diseases will have no effectivetherapies within the next ten years.

Antibiotic Policy: Initial View

An antibiotic policy assumes that antimicrobialtherapy will be rational for the individual patient-"That the antibiotic chosen is likely to cure or preventinfection; that the pathogen is sensitive to it in vitro;that the risk of side effects is minimized; and thatpharmacological and pharmaceutical properties areappropriate." A policy is something superimposed onsuch rational use, taking into account the risk ofdevelopment of resistance, cost, simplicity, and thepersonal preferences of the prescribing clinician. Itdepends on pragmatic consensus, but even that shouldnot prevent a clinician ignoring it in what he believesto be the best interest of an individual patient seekingfor his assistance.

The first civilian antibiotic policies came along withthe emergence of the ‘Hospital Staphylococcus’ in thelate 1950s. Several studies were conducted to reviewhospital infection and to suggest methods for itsprevention. The policy for the treatment ofStaphylococcus aureus infection in operation from1960-67 involved the use of penicillin for the 30-35%of hospital-isolates still susceptible to penicillin, and

erythromycin plus novobiocin for the remainderunless there was resistance to either of them. Inresistant cases methicillin or later cloxacillin was to beused.

By 1967, it was clearly observed that, after its firstappearance in early '60s, and despite its earlyrecognition, methicillin had not become a problem. Soerythromycin and novobiocin, fusidic acids wererestricted and methicillin, cloxacillin or laterflucoxacillin were made freely available. Eventuallythe ‘Hospital Staphylococcus’ was resistant topenicillin, streptomycin, tetracycline,chloramphenicol, erythromycin, novobiocin andneomycin, and if fusidic acid was used, it oftenbecame resistant to that too. However, it was neverresistant to methicillin, although other less commonand less multi-resistant strains were.

The early restriction of erythromycin,methicillin/cloxacillin was accompanied by a fall inresistance rates from 18% to 4%, (returning to 20-25%after 3 years use of erythromycin and novobiocin) andless than 2% simultaneously. It was then thought thatthis delaying resistant effect was due to combined use,which was soon proved to be a wrong assumption.Another personal experience relates tochloramphenicol-resistant Staphylococcus, whichwere, isolated only in the wards of a particular surgeonwho regularly used the drug, and which disappearedimmediately upon the retirement of the surgeon.

Illustration showing the mechanism of antibiotic resistance

Penicillin Mold

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Adaptation of Rational Usage While PrescribingAntibiotics

Indications for Antibiotic Therapy

Definitive therapy : This therapy is for provenbacterial infections. It should be taken into accountseriously that antibiotics are only meant to tackle thebacteria and hence should be restricted for thetreatment of bacterial infection only. Most often thissimple fact is forgotten. Therefore attempts should bemade to confirm the bacterial infection by means ofstaining of secretion/fluids/exudates, culture andsensitivity, serological tests and other necessary testsrather than just depending upon the symptoms andsigns. Based on the reports, a narrow spectrum, leasttoxic, easy-to administer and affordable antibioticshould be prescribed.

Empirical therapy : Empirical antibacterial therapyshould be restricted to critical cases, when time isinadequate for identification and isolation of thebacteria and reasonably strong doubt of bacterialinfection exists. These conditions include septicemicshock/sepsis syndrome, immunocompromisedpatients with severe systemic infection, hectictemperature, neutrophilic leukocytosis, raised ESRetc. In such situations, drugs that cover the mostprobable infective agents should be used.

Prophylactic therapy : Antimicrobial prophylaxis isadministered to susceptible patients to prevent specificinfections that can cause definite detrimental effect.These include antitubercular prophylaxis, antirheumaticprophylaxis, antiendocarditis prophylaxis andprophylactic use of antimicrobials in invasive medical

procedures etc. In all these situations, only narrowspectrum and specific drugs are used. It should beremembered that there is no single prophylaxis toprevent all possible bacterial infections.

Which Antibiotic: A Valuable Question

There are hundreds of antibiotics available today, eachhaving its own spectrum of activity, adverse effect,profile and cost. It is important to consider manyfactors before prescribing an antibacterial agent so asto make the treatment most effective with leastadverse effects, cost and resistance development. Thefollowing factors should be considered whileprescribing an antibiotic.

Site of infection : As a rule of thumb, it can be keptin mind that the infection above the diaphragm arecaused by Cocci and Gram positive organisms andinfections below the diaphragm are caused by Bacilliand Gram negative organisms (although exceptionsare always there).

Upper respiratory tract infections like pharyngitis,tonsillitis, sinusitis, otitis, epiglotis etc. are commonlycaused by organisms like Streptococcus pyogenes, S.peumoniae, Fusobacteria, Peptostreptococci and canbe treated with drugs like penicillins, cephalosporins,and macrolides. Lower respiratory tract infections likebronchitis, pneumonitis, pneumonia, lung abscess etc.are generally caused by the organisms Streptococcusprogenes, S. pneumoniae, Fusobacteria,peptostreptococci, Staphylococcus aureus (rarelymycoplasma, H. influenzae, Moraxella, Klebsiella)etc. and can be managed with the above mentionedantibiotics also including tetracycline. Infectionsbelow the diaphragm (urinary tract infections, intra-abdominal sepsis, pelvic infections etc.) are caused bythe organisms like E. coli,

Colored scanning electron image showingE. coli affected by antibiotics

Agricultural tetracycline being mixed with animal feed

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PUBLIC HEALTH

Klebsiella, Proteus, Pseudomonas, Bacteroides etc.quinolones, aminoglycosides, 3rd generationcephalosporins and metronidazole, alone or incombination are useful in these infections.

Types of infection : Bacterial infections can belocalized or extensive, mild or severe, superficial ordeep seated, acute sub-acute, or chronic andextracellular or intracellular. For extensive, severe,deep seated, chronic and intracellular infections,combination therapy with lipophilic drugs may haveto be used with higher and more frequent doses andfor longer duration of therapy,

Severity of infection : Severe infections (bacteremia /pyemia / sepsis syndrome / septic shock; abscesses inlung / brain / pelvis / intra-abdominal; meningitis /endocraditis / pneumonia / pyelonephritis / peuperalsepsis; severe soft tissue infections/gangrene andhospital acquired infections) can be life threatening andrapidly fatal. In such situations the drug absorption,distribution and excretion could be altered due to tissuehypoxia, changes in hemodynamics, renal and hepaticperfusion, gastro intestinal absorption etc. The drugdynamics can also be altered due to acidosis, alteredpermeability, presence of hydrolyzing enzymes at thesite of infection etc.

Also in such situations, possibility of infection withmultiple organisms and of drug resistance makes thechoice difficult. Therefore, attempts should be madeto identify and isolate the infecting organism from thesite as well as blood by staining and culture. Whiletreating the severe infections, antibiotics should beadministered by only intravenous route to ensureadequate blood levels.

Only bactericidal drugs should be used to ensure fasterclearance of the infection. If the site of infection is

known, narrow spectrum antibiotics are preferred. Ifthe site is not known, attempts should be made tocover all possible organisms including drug resistantStaphylococcus, Pseudomonas and Anaerobes. Acombination of penicillins/3rd generationcephalosporins, aminoglycosides and metronidazolemay be used. The dose should be higher and morefrequent. Whenever possible, a switch to oral therapyshould be established.

Source of infection : Community acquired infectionsare less likely to be resistant whereas hospital acquiredinfections are likely to be resistant and more difficultto treat. An ideal example is pseudomonas infection.

Culture and sensitivity : Ideal management of anysignificant bacterial infection requires culture andsensitivity study of the specimen. If the situationpermits, antibacterials can be started only after thesensitivity report is available. If the patient isresponding to the drug that has already been started, itshould not be changed even if the in vitro report saysotherwise.

Host factors : Age of the patient, immune status,pregnancy and lactation, associated conditions likerenal and hepatic failure, epilepsy etc. should beconsidered while choosing the appropriate antibiotic.

Drug factors : If the patient has prior history ofhypersensitivity, the concerned antibiotic should beavoided. This indicates the importance of proper andthorough history taking of all patients beforeprescribing an antibiotic. Certain adverse reactionswarrant discontinuation of therapy and the doctorshould adequately educate the patients on theseadverse effects. Interactions with food and otherconcomitant drugs should be considered beforeinstituting antibacterial therapy so as to maximizeefficacy and minimize toxicity.

Health workers explaining the appropriate use of antibiotics

A. Enterococcus faecium (the vancomycin resistant form) B. Klebsiella pneumoniae having resistant plasmids

A B

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The cost effectiveness should also be considered whilechoosing an antibiotic. In a developing country likeIndia, Bangladesh with limited budget on healthcare,this does assume significance. It should always beremembered that just because a particular drug isexpensive, it need not be superior to the cheaper ones.As for example, cheaper antibiotics like doxycyclineor co-trimoxazole would be as effective as the morecostly clarithromycin or cephalosporins in themanagement of lower respiratory tract infections.

The Concerns of Antibiotic Use

While there is no doubt about the effectiveness ofantibiotics in combating bacterial illness, it is alsonecessary to implement its rational use as resistance isbecoming a global crisis. Although the majority of

responsibility goes towards the physicians andscientists, the user awareness is also mandatory. Peopleshould be well informed about the inappropriate use ofantibiotics and how it can be dangerous for individualpatient as well as for the whole population.

In the United Kingdom one recent survey suggested15% of patients had been wrongly prescribedantibiotics. Part of the problem has been overuse also.This has given the bacteria constant exposure toantibiotics allowing their genes to evolve rapidly todevelop immunity. In other countries particularly mostof the underdeveloped ones, the situation is mademore difficult by patients being able to buy antibioticswithout any restrictions. This is a global problem andalthough individual efforts will help, an internationaleffort must be made if the remaining antibiotics are tobe kept active against the targeted diseases.

Conclusion

Scientists are working hard to find new ways to defeatbacteria that are increasingly resisting the antibioticsalready available. These range from continuing todevelop new antibiotics to keep up with bacteria's rapidevolution. The response has always been to developnew classes of antibiotics that can tackle the resistantstrains. Until recently the scientists and doctors werewell ahead of resistant bacteria. But with the emergenceof bacteria resistant to even the most powerfulantibiotics, scientists are having a look at otherapproaches, which mainly depends upon therationalization of its usage. This can be achieved by thecombined efforts of the doctors and consumers- TheDoctor Patient Partnership (DPP)- a group already setup in UK urging the consumers to use antibioticsappropriately with its 'Antibiotics: Not a miracle cure!'campaign. This can be developed all over the world. Atthe same time the physicians in general practice shouldtake precautions while prescribing antibiotics as well asupdate the patients about the problems associated withantibiotic misuse or overuse.

References1. Antibiotic Policies: Theory and Practice2. The American Journal of Managed Care 2002;

8:713-7253. U.S. Food and Drug Administration4. World Health Organization5. http://www.textbookofbacteriology.net6. Rational Use of Antibiotics:

rationalmedicine.com7. http://www.bbchealth.com

• Patients who fail to take the full course of antibiotics prescribedfor them : This can aid the rise of drug-resistant germs and isparticularly worrying in the case of serious illnesses. In recentyears, drug-resistant forms of diseases have been noted inmany countries. These are thought to be a result of patientsfailing to complete the course of given antibiotics.

• Patients who forget to take their antibiotics at the timesprescribed: Doctors should explain clearly when and how oftenthe drugs should be taken. The patients should be instructedabout taking the medicine at the same time each day.

• Some patients think they can share other people's antibiotics ortake an unfinished course of antibiotics for another use:Antibiotics are prescribed for a specific illness and for a specificperson, and it should not be shared. The full course of drugsshould be completed so that there should be no leftovers. Aperson may feel well, but there may still be bacteria left in theirbody which cause a recurrence of the illness.

• Patients who suffer from side effects on taking antibiotics: Thepatients should inform their physicians about any problems theyface as the dosage may be too high or they may respond betterto a different course of antibiotics.

A. Doctor describing the use of antibiotic for children B. Person taking antibiotic

Patients’ Note

A B

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VASCULAR MEDICINE

True arterial aneurysms are defined as a 50%increase in the normal diameter of the vessel.Although the aneurysmal process may affect

any large or medium sized artery, the mostcommonly affected vessels are the aorta and iliacarteries, followed by the popliteal, femoral, andcarotid vessels. Aneurysms of the infrarenalabdominal aorta and iliac arteries coexist to such adegree that they may be considered as a singleclinical entity. A true aneurysm involves all threelayers of the blood vessel wall. A false aneurysm ofthe artery is contained only by the outer layers of theblood vessel wall and clot. It is usually a result of aninfection. Inflammatory aneurysms are characterizedby a dense inflammatory infiltrate within the wall ofthe aneurysm.

Aortic Aneurysms

Aortic aneurysm is most common in the abdominalaorta. Abdominal aneurysms usually affect elderlymen (>65 years), with a prevalence of 5%. In England,abdominal aneurysm is responsible for over 11000hospital admissions and 10000 deaths a year.Interestingly, unlike other atherosclerotic vasculardisorders, the prevalence of abdominal aorticaneurysms is increasing rapidly, and aneurysmalrupture is now the 13th commonest cause of death inthe Western world. Each year approximately 15000people die of an abdominal aortic aneurysm in theUnited States.

Clinical Presentation

Although abdominal aneurysms may cause symptomsbecause of pressure on surrounding structures, aboutthree quarters remain asymptomatic at initialdiagnosis. With the exception of vague abdominalpain, clinical symptoms usually result fromembolization or rupture of the aneurysm. Theappearance of microembolic lower limb infarcts in apatient with easily palpable pedal pulses may suggestthe presence of either popliteal or abdominalaneurysms. Additionally, patients with embolizationof mural thrombus from an abdominal aneurysm maypresent with acute limb ischemia due to femoral orpopliteal occlusion.

The diagnostic triad of hypovolemic shock, pulsatileabdominal mass, and abdominal or back pain isencountered in only a minority of patients withruptured abdominal aneurysms. In general, rupturedabdominal aortic aneurysm should be considered inany patient with hypotension and atypical abdominalsymptoms. Similarly, the presence of abdominal painin a patient with a known aneurysm or pulsatile massmust be considered to represent a rapidly expanding orruptured aneurysm and be treated accordingly. In thecommunity setting, the death rate from rupturedabdominal aortic aneurysms is almost 90%, as 80% ofpatients will die before reaching hospital and about5% die during surgery to repair the rupture.

Thoracic aortic aneurysms often go unnoticed becausepatients rarely feel any symptoms. Only half of thepatients complain of symptoms. Possible warning signsinclude pain in the jaw, neck and upper back, chest orback pain, coughing, hoarseness or difficult breathing.

Thoracoabdominal aneurysms extend to a variabledegree from the thoracic aorta into the abdominalaorta. They typically affect the origins of the visceraland renal arteries, which must be reimplanted into thegraft during repair of the aneurysms. Mortality fromrepair of thoracoabdominal aneurysms is significantlyhigher than that for infrarenal surgery.

Inflammatory aneurysms are typically white inappearance and may be densely adherent tosurrounding structures, which could account for theincreased operative mortality in affected patients.Patients typically present with fever, malaise, andabdominal pain.

Arterial Aneurysms

Conventional repair of abdominal aortic aneurysm. Theaneurysmal segment of the aortoiliac segment is replaced with a

prosthetic vascular graft (usually Dacron or ePTFE), which issutured to the normal arterial ‘cuffs’ above and below the

aneurysm

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VASCULAR MEDICINE

Diagnosis

The sensitivity of abdominal palpation to detect aorticaneurysms increases with the diameter of theaneurysm, but palpation is not sufficiently reliable forroutine diagnosis. Similarly, plain abdominalradiography shows a calcified aneurysmal aortic wallin only half of the cases.

The simple diagnostic test is B mode ultrasonography,which gives an accurate assessment of both thediameter and the site of the aneurysm. If moreaccurate morphological data are required to determinethe exact relation of the aneurysm to the visceral orrenal arteries, detailed cross sectional imaging may beobtained by computed tomography or magneticresonance angiography.

The diagnosis of ruptured abdominal aortic aneurysmsrelies on clinical symptoms. Ultrasonography is usedto confirm an aneurysm if it is difficult to palpate.Computed tomography has a low specificity (about75%) for determining the presence of a rupture andadds little information to routine clinical assessment.

Indications for Surgery

Elective surgery : The decision to operate on a patientwith an asymptomatic abdominal aneurysm is basedon a analysis of the risk of aneurysmal rupturecompared with the mortality of elective surgicalrepair. The risk of rupture is related to many factors,but the diameter of the aortic aneurysm hashistorically been used as the principal determinant.

Unfortunately, little information is available on therupture rate of large abdominal aneurysms, but pooled

analysis of existing data suggests that the risk ofrupture increases exponentially in aneurysms above55-60 mm. This has led to a broad surgical consensusthat aneurysms exceeding 55 mm in diameter shouldbe surgically repaired if there are no confoundingfactors that would substantially increase the risk ofelective surgery.

The treatment for smaller aneurysms has recentlybeen clarified by the UK small aneurysm trial, whichstudied 1090 patients with aneurysms of 40-55mm.The study found a 30 operative mortality of 5.8%,mean risk of rupture for small aneurysms of 1% ayear, and no difference in survival between treatmentgroups at two, four, or six years. The cost for earlysurgery was higher than for surveillance, but earlysurgery was associated with improvement in somemeasures of quality of life.

Emergency treatment : Patients with suspectedruptured aneurysms should be considered for

Computed tomogram showing large infrarenal abdominal aortic aneurysm

Annual rupture rates of abdominal aortic aneurysms according to size (based on pooled available data)

Endovascular aneurysm repair. The aneurysm sac is excluded byan endograft, which is introduced through a remotearteriotomy

and anchored above and below the aneurysm sac

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emergency surgical repair. Several studies havelooked at preoperative risk factors and survival afteremergency repair of an aneurysm. Although there isno precise scoring system that will allow accurateprediction of survival, the presence of severalpredictive factors (age>80 years, unconsciousness,low hemoglobin concentration, cardiac arrest, severecardiorespiratory disease) can be used to determinepatients in whom the risk of dying during surgeryapproaches 100%.

Patients with symptomatic aneurysms should betreated as urgent cases and have the aneurysmrepaired. The etiology of pain from abdominalaneurysms is not well understood, although it has beenattributed to stretching of the aneurysm sac or severeinflammation within the aneurysm wall.

Conventional Surgical Repair

Traditional surgical repair for asymptomaticabdominal aortic aneurysms involve exposure of theaneurysmal segment with a prosthetic graft. Graftreplacement is an effective, durable procedure, andmost centres report 30 day mortality of about 5%,although this varies with the volume of work and typeof hospital. The mortality associated with surgicalrepair of aneurysms is closely related to the "fitness"of the patient for surgery; patients with severecardiorespiratory disease have a perioperativemortality approaching 40%, with most deaths causedby cardiac events.

Endovascular Repair

One of the major developments in vascular surgeryover the past five years has been the introduction ofendovascular repair of aneurysms. This technique usesan endoprosthesis, which is delivered through thefemoral arteries, to exclude an aneurysm from the

Aortoiliac aneurysm before exclusion by a bifurcated endovascular graft

• No need for abdominal incision• Avoidance of aortic cross clamping• No retroperitoneal dissection• Improved perioperative cardiorespiratory

function• Reduction in metabolic stress response to

aortic aneurysm repair• Improved renal and gastrointestinal function• Reduced hospital stay

• High blood pressure• Smoking• High cholesterol• Obesity• Emphysema• Genetic factors• Male gender

• Diameter of aneurysm• Diastolic blood pressure• Chronic obstructive pulmonary disease• Smoking• Family history of ruptured aneurysm• Expansion rate• Intrinsic biology-inflammation within the

aortic wall• Thrombus-free surface area of aneurysm sac

Inflammatory abdominal aneurysm. The aneurysm is typicallywhite in appearance and densely adherent to surrounding

structures. The duodenum is being mobilized from the aneurysmsac by sharp dissection

Potential Advantages of Endovascular RepairOver Conventional Surgery

Risk Factors for Developing and Aortic Aneurysm

Factors Predisposing to Rupture of AbdominalAortic Aneurysms

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circulation. The endograft is secured to the normalcalibre aorta and iliac arteries using metallicexpandable stents and relies on subsequent thrombosisof the aneurysm to abolish the risk of rupture.Endovascular repair has several theoreticaladvantages over conventional surgery, and earlyevidence suggests that endovascular surgery is betterfor patients with coexistent disease, who would be athigh risk for conventional surgery. However, the longterm durability of endovascular techniques isunknown, although experience so far shows that up toa quarter of patients undergoing endovascularaneurysm repair will require subsequent endovascularinterventions to ensure regression of the aneurysmalsac. A multicentre trial of endovascular repair andconventional surgery has already been started in theUnited Kingdom.

Screening and Medical Treatment

Ultrasonography-based screening programs to detectand treat asymptomatic aneurysms have been proposedas a mechanism to reduce the mortality from rupturedabdominal aortic aneurysms. Screening studies report a2.5% prevalence of abdominal aortic aneurysms largerthan 40 mm in men aged over 60 years. Advocates ofcommunity screening have suggested that a singleabdominal scan in men aged 65 would exclude 90% ofthe population from future aneurysm rupture. And longterm follow up of screened and control populations inChichester showed 85% reduction in rupture in thescreened group. A multicentre randomized trial iscurrently investigating the cost-effectiveness ofcommunity based aneurysm screening. One of theproblems with screening programs is that it identifiesmany people with small aneurysm. These patients arenot offered any form of treatment other thanultrasonographic surveillance, which may haveimplications for quality of life.

However, recent studies have begun to elucidate themolecular and biochemical mechanisms of aneurysmformation, and clinical trials of the effectiveness ofseveral groups of drugs to reduce expansion of smallaneurysms are likely. The most promising of thesedrugs in experimental studies have been inhibitors ofmatrix metalloproteinases.

Peripheral Aneurysms

Popliteal aneurysms comprize 80% of all peripheralaneurysms and usually exceed 20 mm in diameter.They are associated with aortic aneurysms (40% of

cases), and are frequently bilateral (50%). Patientswith popliteal aneurysms usually present with acutelimb ischemia secondary to aneurysm thrombosis ordistal embolisation. A diagnosis of poplitealaneurysms is suggested by easily palpable poplitealpulses and confirmed by duplex ultrasonography.

Patients who develop acute limb ischemia due topopliteal thrombosis or embolism have a relativelypoor prognosis (15% amputation rate) because ofocclusion of the run off vessels. In these cases patientsshould have saphenous vein bypass and ligation of thepopliteal aneurysm with clearance of the cruralvessels by balloon thrombectomy or thrombolysis.The indications for elective surgery for asymptomaticpopliteal aneurysms are based on suggestive evidenceonly, with most clinicians opting for surgicaltreatment when the aneurysm exceeds 25 mm indiameter. Results of bypass of asymptomatic poplitealaneurysms are excellent, with five year graft patencyof 80% and limb salvage of 98%.

Femoral artery aneurysms are the second commonestperipheral aneurysm. Patients present with localpressure symptoms, thrombosis, or distalembolization. Surgical treatment of true femoralaneurysms relies on the principles of excluding theaneurysm and restoration of blood flow in the limb.

References1. British Medical Journal 2000; 320:1193-11962. http://www.myoclinic.com3. http://www.emedicine.com4. http://www.clevelandclinic.org

Computed tomogram of thoracoabdominal aneurysm

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ENVIRONMENTAL HEALTH

In 1969, the Apollo moon shot providedextraordinary photographs of the planet Earthtransforming the thoughts about the biosphere and

its limits. From then, increasing in understanding ofclimate change is transforming the views about theboundaries and determinants of human health. Whilethe personal health of the individual are mostly relatedto prudent behavior, heredity, occupation, localenvironmental exposures, and health care access;sustained population health requires the life-supporting 'services' of the biosphere. Not only thehumans but also all animal species depend on suppliesof food and water, freedom from excess infectiousdisease, and the physical safety and comfort conferredby climate stability. The world's climate system is thefundamental of this life-support.

Impacts of Climate Change on Human Health : Fromthe tropics to the arctic, both climate and weather havepowerful impacts, both direct and indirect, on humanlife. Marked short-term fluctuations in weather cancause acute adverse health effects. Extremes of bothheat and cold can cause potentially fatal illnesses suchas heat stress or hypothermia as well as increasing deathrates from heart and respiratory diseases. In cities,stagnant weather conditions can trap both warm air andair pollutants leading to smog episodes with significanthealth impacts.

The impacts of climate on human health will not beevenly distributed around the world. Populations ofdeveloping countries, particularly in small islandstates, arid and high mountain zones, and in denselypopulated coastal areas, are considered to beparticularly vulnerable. Some weather extremes, suchas heavy rains, floods and hurricanes also have severeimpacts on health. Approximately 600,000 deathsoccurred world-wide as a result of weather relatednatural disasters in the 1990s and some 95% of thosewere in poor underdeveloped countries. In additionmany important infectious diseases are highlysensitive to changing temperatures and precipitation.

These climate-sensitive diseases are among the largestglobal killers. Diarrhea, malaria and protein-energymalnutrition caused more than 3.3 million deathsglobally in 2002, with 29% of these deaths occurringin the region of Africa.

The Global Warming Issue: Human activities,particularly burning of fossil fuels, have releasedsufficient quantities of Carbon-di-oxide (CO2) andother green house gases over the last 50 yearsresulting in global warming. As the global emission ofCO2 is still increasing, this situation is likely toworsen furthermore ultimately making a hostileenvironment for all living creatures of earth.

Actions Need to be Taken Now or Never: The healthimpacts of climate change will be difficult to reversein a few years or decades. Yet, many of these possibleimpacts can be avoided or at least controlled. Thereare established steps in health and related sectors toreduce the exposure to and the effect of changingclimate. For example, controlling disease vectors,reducing pollution from transport, and efficient landuse and water management are well-known and testedmeasures that can help. Moreover, many of the stepsare needed to prevent climate change with the aim ofgaining positive health impacts. For example,increased use of bicycles and public transport insteadof personal cars in industrialized countries will reducegreenhouse gas emissions. It will also improve airquality and lead to better respiratory health and fewerpremature deaths.

With climate change already underway, there is needto assess vulnerabilities and identify interventionoptions. Early planning for health can reduce futureadverse health impacts. The optimal solution however,lies with the governments, society, and individuals;and requires changes in behavior, technologies andpractices to enable a transition to sustainability.

Source: World Health Organization

Climate Change and Human Health- Risks and Responses

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ENVIRONMENTAL HEALTH

Climate change is sometimes debated as if itaffected only the planet and not the humansliving on it. Climate change endangers the

quality and availability of water and food, thefundamental determinants of nutrition and health. It iscausing more frequent and more severe storms, heatwaves, droughts and floods, while worsening thequality of air. The result is an upsurge in humansuffering caused by injury, disease, malnutrition anddeath. This year's World Health Day is an opportunityto broaden this view by spotlighting the major healththreats of global warming.

This year World Health Day is presented with a bannerof 'Protecting Health From Climate Change' in orderto focus this delicate and controversial issue aroundthe world. The objective of World Health Day 2008 isto catalyze public participation in the global campaignto protect health from the adverse effects of climatechange. World Health Organization (WHO) aims toput public health at the center of the United Nations,agenda on climate change. This is an opportunity forthe international agencies, non-governmentalorganizations, and governments as well as WHO to:

• Establish links between climate change and healthand other development areas such as environment,food, energy and transport

• Hold events or activities in countries to publicizeissues related to the impact of climate change onhealth

• Involve as wide a spectrum of the world populationas possible in efforts to stabilize climate change

• Create advocacy campaigns for generatingmomentum that compels governments, theinternational community, civil society andindividuals to take action

• Protect poor and vulnerable populations from theeffects of climate change, especially in Africa

Climate change is real, it is accelerating and itthreatens the existence of all living things on earthincluding the mankind. That is why WHO recognizesthe urgent need to support countries in devising waysto cope such crisis. Citizens also need to be fullyinformed of the health issues as it is their concern toowhich can spur policy-makers to take the right actionsin time.

Source: World Health Organization

World Health Day 2008: Protecting Health From Climate Change

• Raise awareness and public understanding ofthe global and locally relevant healthconsequences of climate change.

• Advocate for interdisciplinary and intersectoralpartnerships from the local to internationallevels that seek to improve health through rapiddeployment of mitigation strategies to stabilizeclimate change and development of proactiveadaptation programs to minimize healthimpacts.

• Generate effective actions by localcommunities, organizations, health systems andgovernments to reduce the impact of climatechange on health through urgent application ofmitigation and adaptation techniques.

• Demonstrate the health community's role infacing the challenges globally and in regions,countries and communities.

• Spark commitment and action amonggovernments, international organizations,donors, civil society, businesses andcommunities (especially among young people)to anchor health are the heart of the climatechange agenda.

Goals for World Health Day 2008

14

CASE REPORT

A59-year-old man with a medical history ofhypertension, hyperlipidemia, and coronaryartery disease presented with transient,

painless visual obscuration in the left eye. He wasreferred for retinal evaluation. His retinal examinationon left eye showed multiple, tiny refractile, retinalarteriolar cholesterol emboli and a saddle embolussuperior to the optic nerve (image A). While taking hishistory he stated that two months earlier, he hadundergone placement of a stent in the left carotidartery for severe stenosis. He was receivingantiplatelet therapy. He had also gone through aroutine eye check-up two years earlier, and thefindings were unremarkable.

Two months later repeat examination showed anincrease in the number of cholesterol emboli (imageB). The patient's visual acuity was unchanged (20/25bilaterally). Four weeks later, a sudden painless loss ofthe superior visual field occurred. Examinationrevealed whitening of the inferior macular region(image C), a finding that was consistent with anocclusion at the second major bifurcation of theinferior temporal branch of the retinal artery. Aftercarotid stenting, ongoing deposition of retinal embolimay occur. The patient was left with a deficit in thesuperior visual field.

Retinal Arteriolar Cholesterol Emboli are the mostcommon types of cholesterol embolus, which has beenlinked to ulcerated atherosclerotic plaques at the carotidartery bulb. This is also caused by dissemination inarterial blood circulation from an ulceratedatheromatous plaque, a process frequently identifiedafter cardiac catheterization, coronary angioplasty,arteriography or heart surgery. This may appear inpatients using anticoagulants or fibrinolytic medicationswith vascular risk factors (hypertension, diabetes,family history, dislipemia, tobacco smoking etc.).

These emboli are bright orange, yellow or copper-colored fragments and are usually seen at arteriolarbifurcation, Owing to their brightness, they are oftenconspicuous on dilated ocular examination and areperiodically identified in eye clinics. Because of theirthin, flat shape, the cholesterol crystals do not occludethe involved vessels and are often asymptomatic.

Source: New England Journal of Medicine

Retinal Arteriolar CholesterolEmboli

A

B

C

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CASE REPORT

A76-year-old man with renal failure fromNephroangiosclerosis received a kidneytransplant from a deceased donor. The

transplant was functioning well when the patientunderwent a radical laryngopharyngoesophagectomy,with colopharyngeal anastomosis, for esophagealcarcinoma. He was transferred to the intensive careunit (ICU) five days after surgery. While in ICU, hisurine was noted to be green with unremarkablesediment and a creatinine level of 1.4 mg per deciliter(123.8 µmol per liter).

Owing to the presence of mucous drainage from theproximal surgical wound, the patient had received aninjection of methylene blue (also called anilline violetand tetramethyl-thionine chloride) through hisnasogastric tube, to look for a possible fistula. Afistula was found.

Methylene blue is a water-soluble dye that can be usedto assess whether a fistula is present or used as amedication. It is filtered by the kidneys and has nopathologic effects but may cause the urine to have abluish or greenish color. Once the dye has beenpassed (after 2 days in this patient), the color of the

urine returns to normal. The patient had no clinicalproblems after the dye was passed. Some medicationssuch as methocarbamol, amitriptyline and triamterenemay also cause bluish or greenish discoloration ofurine.

Positive urine and blood assays of methylene andleukomethylene blue were obtained from 9 volunteerswith normal colonic and renal function after a 100 ml,methylene blue enema (50 mg.). The studyconclusively demonstrates that methylene blue isabsorbed by rectal mucosa and excreted by thekidneys as a colored dye in the urine.

Source: New England Journal of Medicine

Green Urine !

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FACT FILE

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1

10 Facts About Diabetes Mellitus

There is an emerging global epidemic ofdiabetes that can be traced back torapid increases in overweight, obesityand physical inactivity.

Total deaths from diabetes areprojected to rise by more than 50% inthe next 10 years. Most notably, theyare projected to increase by over 80%in upper-middle income countries.

Type 1 diabetes is characterized by alack of insulin production and type 2diabetes results from the body'sineffective use of insulin.

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FACT FILE

6

5

10 Facts About Diabetes Mellitus

Reports of type 2 diabetes inchildren (previously rare) haveincreased worldwide. In somecountries, it accounts for almosthalf of newly diagnosed cases inchildren and adolescents.

A third type of diabetes is gestationaldiabetes. Gestational diabetes is

characterized by hyperglycemia, orraised blood sugar, which is first

recognized during pregnancy.

4

Type 2 diabetes is much morecommon than type 1 diabetes, and

accounts for around 90% of alldiabetes worldwide.

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FACT FILE

8

9

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10 Facts About Diabetes Mellitus

Source : World Health Organization

Diabetes can be prevented. Thirtyminutes of moderate-intensity physicalactivity on most days and a healthydiet can drastically reduce the risk ofdeveloping type 2 diabetes.

Lack of awareness about diabetes,combined with insufficient access tohealth services, can lead tocomplications such as blindness,amputation and kidney failure.

Eighty percent of diabetes deathsare now occurring in low andmiddle-income countries.

7In 2005, 1.1 million people died fromdiabetes. The full impact is muchlarger, because although peoplemay live for years with diabetes,their cause of death is oftenrecorded as heart diseases orkidney failure.

19

ONCOLOGY

Pain is a complex phenomenon that is thesubjective end point of a variety of physical andnon-physical factors. Physical pain may be one

of the several symptoms of many diseases varyingfrom simple to complex illness, life-threateningemergencies and the deadly disease of today's society- cancer. Pain occurs in up to 70% of patients withadvanced cancer and in about 65% of patients dyingfrom non-malignant diseases. In about 10% of thesepatients the pain is difficult to control.

Assessment of Cancer Pain

Cancer pain is mostly caused by the tumor pressing onbones, nerves or other organs. Sometimes pain may berelated to the treatment. Such as chemotherapy drugscan cause numbness and tingling of the hand and feetor a burning sensation at the site of injection.

Careful, comprehensive assessment of cancer pain isabsolutely essential for managing and providing the besttreatment. With effective assessment and a systematicapproach to the choice of analgesics using the WorldHealth Organization's three step analgesic ladder, over80% of cancer pain can be controlled with less expensivedrugs that can be self administered by mouth.

There are three types of pain, based on where in thebody the pain is felt: somatic, visceral andneuropathic. Most cancer patients experiences bothsomatic and visceral pain. Only about 15-20% of allcancer patients report neuropathic pain. Cancer paincan be either acute (sudden and severe) or chronic(lasting more than 3 months). According to theAmerican Cancer Society, chronic cancer pain ofteninvolves persistent and breakthrough pain.

Pain Assessment Tools

The pain scale is a tool, commonly used to describe theintensity of the pain or how much pain the patient isfeeling. In Numerical rating scale, the person is askedto identify how much pain they are having by choosinga number from 0 (no pain) to 10 (the worst painimaginable). Visual analogue scale is a straight linewith the left end of the line representing no pain and theright end of the line representing the worst pain.Patients are asked to mark on the line where they thinktheir pain is. The categorical scale has four categories:

none, mild, moderate, and severe. Patients are asked toselect the category that best describes their pain. Thepain faces scale uses six faces with differentexpressions on each face. Each face is a person whofeels happy because of having no pain or feels sad forhaving some or a lot of pain. The patient is asked tochoose the face that best describes how he or she isfeeling. The pain faces scale is commonly used incases of pediatric patients particularly below the ageof 3 years.

Analgesics: Dwelling the Cancer Pain

In the 19th century, cancer pain came to dwell under anew domain-science-paving the way for advances inits therapy. Physician-scientists discovered thatopium, morphine, codeine, and cocaine could be usedfor the purpose of relieving cancer pain. These drugseventually led to the development of aspirin. To thisday, aspirin is the most commonly used pain reliever.

Analgesics remain the key in managing cancer pain.The choice of drug should be based on the severity ofpain, not the stage of disease. Drugs should be givenin standard doses at regular intervals in a stepwisefashion. The decision to use an opioid for severe painshould be based on severity of pain and not onprognosis.

An adjuvant analgesic is a drug whose primaryindication is for something other than pain but that hasan analgesic effect in some painful conditions. Adjuvantanalgesic drugs may be usefully added at any stage.

Management of Cancer Pain

Cancer pain can be managed in several ways includingtreating the underlying cancer with chemotherapy,

Controlling Cancer Pain

Chemotherapeutic agents

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ONCOLOGY

radiation therapy, surgery or other therapy. Drugtherapies are the main factor to treat cancer pain. Theyinclude the use of opioids, non-opioids, and adjuvantanalgesics. There are also some non-pharmacologicalapproaches towards dealing cancer pain. World HealthOrganization has developed a standardized cancerpain treatment plan now recognized worldwide.Studies show that 70-90% of cancer pain can beeffectively treated by using this system.

Non-opioids: These medicines are excellent inrelieving bone pain, superficial pain, muscle pain etc.They are the first choice for mild pain and also useswith other types of pain medications to provide greaterpain relief. Side effects vary, but general effectsinclude gastrointestinal toxicity, ulcers and bleeding.Patients with bleeding or clotting disorders must betreated cautiously with non-opioids.

Opioids: Opioids are so far the strongest of allanalgesics. They include codeine, oxycodone,morphine, fentanyl, and hydromorphine. All areexcellent for relieving cancer pain. Opioids arecategorized on their onset and duration of action. Theweak opioids are used for less severe pain and oftencombined with non-opioids.

Surgery, chemotherapy & radiation therapy:Although these are used to prevent or control furthercomplications of cancer, also applied for reducing thetumor size thus indirectly providing some sort of reliefof pain. In patients with breast or prostate cancer,hormone therapy can reduce the size of a tumor inpainful locations such as the bone or soft tissue. Thisis used to relieve the pain caused by cancer that hasspread to the bone. The majority of patients with bonemetastasis have significant relief of their pain withradiation therapy.

Pain relieving procedures: For localized pain thatdoes not respond to other measures, a local anesthetic,usually combined with steroid, is injected into a nerve,nerve root, or spinal cord space to block pain. Incertain situations, the nerves may be cut to block thepain. When a nerve cannot be blocked, anesthesia canbe achieved by injecting opioids into the spinal spacesusing a pump to deliver a constant amount of drug.Pacemakers can be used to send electrical signals tothe nerves to block pain.

Non-pharmacological techniques for pain relief:There are several non-pharmacological techniques forthe management of cancer pain particularlyneuropahtic pain. Psychological techniques such ascognitive behavioral therapies include simplerelaxation, hypnosis and biofeedback. Acupuncturehas been used successfully for centuries.Transcutaneous electrical nerve stimulation (TENS)has similar mechanism of action of acupuncture.Herbal medicine and homeopathy are widely used forpain but often with little evidence for efficacy.

Morphine for Severe Pain

Morphine is the most commonly used opioid forsevere pain. When possible, oral administration ispreferred. The rectal bioavailability of morphine issimilar to its oral bioavailability. Subcutaneousinfusion is another convenient option for opioids. Therelative potency is increased when it is givenparenterally. Patients rarely require intravenousadministration of morphine, however, this may beappropriate for children.

The simplest method is to prescribe a regular fourhourly doses, but extra doses of the same size are

Factors affecting patient's perceptions of pain

Cancer patients receiving chemotherapy

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ONCOLOGY

allowed for breakthrough pain as often as necessary.Patients with advancing disease and increasing painmay require continual adjustment of dose. Once thedose is established, maintenance should be with acontrolled release preparation. This is available as aonce or twice daily preparation lasting for 24 or 12hours respectively.

Requirements for increasing doses of morphine canusually be explained by progressive disease ratherthan tolerance. Psychological dependence or addictionis not a problem, except in some patients with pre-existing addiction. If alternative methods of paincontrol are used the dose of analgesic can usually bereduced. Physical dependence can occur and this

physiological response can manifest itself as a flu-likeillness in some patients if an opioid is discontinuedsuddenly. The dose of opioid that can be toleratedvaries widely both between and within individuals.

Although toxicity can be frightening and lifethreatening, it is usually reversible if it is diagnosedearly. Opioid toxicity may present as subtle agitation,seeing shadows at the periphery of visual field, vividdreams, visual and auditory hallucinations, confusion,and myoclonic jerks. Agitated confusion may bemisinterpreted as uncontrolled pain and furtheropioids are given. Management includes reducing thedose of opioid, ensuring adequate hydration andtreating the agitation with haloperidol (1.5-3 mg orallyor subcutaneously, repeated hourly as needed basis). Iftoxicity is severe and opioid analgesia is still needed,switching to other opioid usually leads to a fasterrecovery. If a different opioid is required, a lower dosethat gives equal analgesia should be preferred.

Difficult Pain: Pain that Poorly Responds toOpioids

Neuropathic pain: Neuropathic pain is caused bydamage to the peripheral or central nervous system. Itmay be described as aching, burning, shooting, orstabbing and may be associated with abnormalsensation; even normal touch is perceived as painful.

Cancer patient receiving radiotherapy

Commonly Used Adjuvant Analgesics

Drugs Dose Indications Side effects

Non-steroidal anti-inflammatories (NSAID)-for example, diclofenac

50mg oral every 8 hour(slow release 75mg every12 hours); 100mg perrectum once a day

Bone metastases, softtissue infiltration, liverpain, inflammatory pain

Gastric irritation and bleeding,fluid retention, headache;caution in renal impairment

Steroids- for example,dexamethasone

8-16mg/day; use inmorning; titrate down tolowest dose that controlspain

Raised intracranialpressure, nervecompression, soft tissueinfiltration, liver pain

Gastric irritation if used withNSAID, fluid retention,confusion, Cushingoidappearance, candidiasis,hyperglycemia

Gabapentin 100-300mg at night (startingdose) (titrate to 600 mg every 8 hours;higher dose may be needed)

Nerve pain of anycause

Mild sedation. Tremor,confusion

Amitriptyline (evidencefor all tricyclics)

25mg at night (starting dose)10mg nightly (in elderlypatients)

Nerve pain of anycause

Sedation, dizziness, confusion,dry mouth, constipation,urinary retention; avoid inpatients with cardiac disease

Carbamazepine (evidencefor all anticonvulsants)

100-200mg at night(starting dose)

Nerve pain of anycause

Vertigo, sedation,constipation, rash

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ONCOLOGY

It may be caused not only by tumor invasion orcompression but also by surgery, radiotherapy, andchemotherapy. If neuropathic pain doses not respondto opioids, early addition of adjuvant analgesicsshould be considered. The adjuvant should be chosenfor an individual case based on all symptoms andpotential side effects. Doses should be titrated tobalance analgesia with adverse effects. If titration hasreached a limit and pain has not responded asexpected, then a second adjuvant may be added. Acommon example of combining adjuvants isgabapentin, which at maximum tolerated dose cansometimes be reduced to allow the addition ofamitriptyline.Episodic pain: The term episodic pain is used todescribe any acute transient pain that is severe and hasan intensity that flares over baseline. Episodic painthus encompasses breakthrough pain and incidentpain. Breakthrough pain includes pain returningbefore the next dose of opioid. Incident pain is usuallydefined as that occurring due to a voluntary action,such as movement or passing urine or stool. Pain dueto bony metastases exacerbated by movement orweight bearing can be particularly problematic.Opioid analgesics along with non-steroidal anti-inflammatory drugs are the mainstay of treatment.Increasing the dose of opioid is not very helpful as adose sufficient to make movement possible is toosedating when the patient is resting. Rescue orbreakthrough doses of normal release opioid areusually used in anticipation of movement, along withnon-drug measures such as radiotherapy, possiblesurgery and appropriate aids and appliances.

References1. British Medical Journal 2006; 332:1023-10242. British Medical Journal 2006; 332:1081-10833. http://www.cancerpain.org4. http://www.oncologychannel.com5. American Cancer Society6. National Comprehensive Cancer Network

• The degree of responsiveness of the pain toopioid analgesia

• Previous exposure to opioids• Rate of titration of the dose• Concomitant medication• Concomitant disease• Genetic factors, biochemical factors such as

renal function

Factors that Affect the Tolerability of Opioids

WHO Analgesic Ladder

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NEWS

FROM

INTERNET

Lowering Blood Pressure after IntracranialHemorrhage May Improve Prognosis

A lthough current strategies recommendlowering very high blood pressure as soon aspossible after an intracranial hemorrhage, there

is little evidence that suggests when to begin treatmentor how much to lower blood pressure. To try to clarifythis issue, the researchers began a randomized pilottrial in hospitals in Australia, China and South Koreabetween November 2005 and August 2007. The studycompared an intensive blood pressure-loweringstrategy (n = 203), or target systolic blood pressure 140mm Hg, with the recommended best practice standardstrategy (n = 201), or target systolic blood pressure 180mm Hg, in participants with spontaneous intracerebralhemorrhage [confirmed by computerized tomography(CT)]. CT scans were repeated 24 hours after thebeginning of the treatment to check for growth ofhematoma. In the intensive treatment group, hematomagrowth was 13.7% compared with 36.3% in the non-intensive group (P = 0.04). The groups did not differ inthe numbers of adverse side effects from treatment.They also did not differ in any of the secondary clinicaloutcomes that measured the number of deaths, thedegrees of disability, physical, and mental functioning;and quality of life in survivors at 90 days. Theresearchers concluded that because intravenoustreatment to lower blood pressure is relativelystraightforward, is not hazardous, and is of low cost, ifapplied widely these effects could translate into majorabsolute benefits. The researchers plan to proceed withthe next phase of the trial, which will assess the effectof the intensive treatment on the key clinical outcomeof death and dependency in 2,800 patients who havehad an intracranial hemorrhage from sites around theworld.

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United States Food and Drug Administration(FDA) Approved New Medical Adhesive to Treat

Burn Patients

T he US FDA approved a new medical adhesivecalled Artiss for use in attaching skin graftsonto burn patients. Fibrin sealants are tissue

adhesives that contain the protein fibrinogen andthrombin, which are essential in the clotting of blood.Artiss (Fibrin Sealant, VH S/D 4) differs from otherfibrin sealants in that it contains a lower concentrationof thrombin. This lower concentration allows surgeonsmore time to position skin grafts over burns before thegraft begins to adhere to the skin. Artiss also containsaprotinin, a synthetic protein that delays the breakdown of blood clots. The researchers said that theapproval of Artiss could help surgeons using a fibrinsealant to fine tune graft placement on burn sites. Thefibrinogen and thrombin proteins in Artiss are derivedfrom human plasma. Both proteins undergopurification and virus inactivation treatments. During amulticenter clinical trial, investigators evaluated Artissfor its ability to attach skin grafts on two wound sitesfor 138 patients. At one test site, the skin graft wasfixed with Artiss; at the other test site, the graft wasfixed with surgical staples. The results showed thatArtiss was, within a statistical error, as good as staplesto attain complete wound closure. Frequent adverseevents, seen in both treatment groups, includedbleeding and fluid collection in the tissues, both ofwhich are common during skin grafting procedures.

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Poststroke Clot-Busting Therapy Beneficial forPatients on Aspirin

A ccording to a study, patients given a clot-busting drug following stroke appear to havebetter outcomes if they were already taking

antiplatelet medications, despite an apparent increasedrisk for bleeding in the brain. The researchers studied301 patients who received tissue plasminogen activator(tPA) therapy following stroke between 2002 and 2006.Of those, 89 had used antiplatelet drugs prior toreceiving tPA. Symptomatic brain hemorrhagesoccurred in 12 patients who had received antiplatelettherapy (13.5%) and in 6 patients who had not (2.8%).Patients who had been taking antiplatelet therapy had ahigher risk for symptomatic brain hemorrhages. Theresearchers said that despite this increased risk, priorantiplatelet therapy increased the odds of a favorableoutcome, defined as the ability to independently carryout activities of daily living after 3 months. Therefore,the study suggests that tPA treatment should not bewithheld from patients receiving antiplatelet therapy.They also said that Aspirin remains active for 4 to 6days and might prevent an additional blood vesselblockage from occurring following tPA therapy, leadingto the observed improved outcomes. They concludedthat larger prospective studies are warranted to furtherinvestigate the influence of antiplatelet therapy onoutcome after thrombolytic therapy for acute ischemicstroke.

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