IJCP Oct ober 2012

Volume 23, Number 5, October 2012

Online Submission

Advisory Bodies

IJCP Group of PublicationsDr Sanjiv Chopra

Prof. of Medicine & Faculty Dean Harvard Medical SchoolGroup Consultant Editor

Dr Deepak ChopraChief Editorial Advisor

Dr KK AggarwalCMD, Publisher, Group Editor-in-Chief

Dr Veena AggarwalMD, Group Executive Editor

Heart Care Foundation of India

Non-Resident Indians Chamber of Commerce & IndustryWorld Fellowship of Religions

IJCP Editorial BoardObstetrics and Gynaecology Dr Alka Kriplani Dr Thankam Verma, Dr Kamala SelvarajCardiology Dr Praveen Chandra, Dr SK ParasharPaediatrics Dr Swati Y Bhave Dr Balraj Singh Yadav Dr Vishesh KumarDiabetology Dr Vijay Viswanathan Dr CR Anand Moses, Dr Sidhartha Das Dr A Ramachandran, Dr Samith A ShettyENT Dr Jasveer SinghDentistry Dr KMK Masthan Dr Rajesh ChandnaGastroenterology Dr Ajay KumarDermatology Dr Hasmukh J ShroffNephrology Dr Georgi AbrahamNeurology Dr V NagarajanJournal of Applied Medicine & Surgery Dr SM Rajendran

FROM THE DESK OF GROuP EDITOR-IN-CHIEF

245 Endocrine Society issues Guidelines for Hypertriglyceridemia

KK Aggarwal

REVIEw ARTIClE

246 A Critical Insight into the Present and upcoming Pharmacological Therapies for Treatment of GERD

Vivek A, Garima Bhutani

254 Is Essential Medicine Concept for Voluntary Organizations Only?

Dixon Thomas, G Seetharam, Y Padmanabha Reddy, Gerardo Alvarez-Uria

ORIGINAl STuDy

261 Keracnyl® in the Management of Acne P Khandeparkar, R Chavda, V Durosier, Q Mukaddam,

R Kharkar

269 Modulating Postoperative Pain Relief in Cesarean Section with use of Transdermal Diclofenac Patch

N Gupta, R Gupta, S Agarwal, A Agarwal, SN Gupta, V Thawani

ClINICAl STuDy

272 Study of the Prevalence and Clinical Profile of Diabetes in the urban Population of Dibrugarh

RK Kotokey, Abul Kalam Azad PK, Himanab Jyoti Das, Aneesh Ashok, Kamal Rajkhowa, Vishu Kumar, Tridip Kumar Das

Anand Gopal BhatnagarEditorial Anchor

This journal is indexed in IndMED (http://indmed.nic.in) and full-text of articles are included in medIND databases (http://mednic.in) hosted by National

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The purpose of IJCP Academy of CME is to serve the medical profession and provide print continuing medical education as a part of their social commitment. The information and opinions presented in IJCP group publications reflect the views of the authors, not those of the journal, unless so stated. Advertising is accepted only if judged to be in harmony with the purpose of the journal; however, IJCP group reserves the right to reject any advertising at its sole discretion. Neither acceptance nor rejection constitutes an endorsement by IJCP group of a particular policy, product or procedure. We believe that readers need to be aware of any affiliation or financial relationship (employment, consultancies, stock ownership, honoraria, etc.) between an author and any organization or entity that has a direct financial interest in the subject matter or materials the author is writing about. We inform the reader of any pertinent relationships disclosed. A disclosure statement, where appropriate, is published at the end of the relevant article.

Note: Indian Journal of Clinical Practice does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature in this issue.

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ORIGINAl ARTIClE

279 Clinico-etiological and EEG Profile of Neonatal Seizures

Shwetal Bhatt, Nita Raju, Supriya Phanse, Sangita V Patel, Geetika Madan, Sanjeev Mehta, Chetan Trivedi

CASE REPORT

286 Evaluation of a Case of Penetrating Ocular Injury Jitender Phogat, Vivek Gagneja, Sumit Sachdeva, Mukesh Rathi

PRACTICE GuIDElINES

289 PHS updates Smoking Cessation Guideline

PHOTO quIz

291 linear lesions in a Neonate

MEDIlAw

293 Illegal Pathlabs MC Gupta

lIGHTER READING

294 lighter Side of Medicine

245IndianJournalofClinicalPractice, Vol. 23, No. 5, October 2012

Dr KK AggarwalPadma Shri and Dr BC Roy National AwardeeSr. Physician and Cardiologist, Moolchand Medcity, New DelhiPresident, Heart Care Foundation of IndiaGroup Editor-in-Chief, IJCP Group and eMedinewSChairman Ethical Committee, Delhi Medical CouncilDirector, IMA AKN Sinha Institute (08-09)Hony. Finance Secretary, IMA (07-08)Chairman, IMA AMS (06-07)President, Delhi Medical Association (05-06)[email protected]://twitter.com/DrKKAggarwalKrishan Kumar Aggarwal (Facebook)

fromthedeskofgrouPedItor-In-ChIef

Endocrine Society issues Guidelines for Hypertriglyceridemia

The Endocrine Society Guideline for the evaluation of patients with hypertriglyceridemia recommends that the diagnosis be based on fasting triglyceride levels.At least every five years, adults should be screened for hypertriglyceridemia as part of a lipid panel.To facilitate assessment of cardiovascular risk, mild and moderate hypertriglyceridemia, defined as triglyceride levels of 150-999 mg/dl, should be diagnosed, as this condition may be a risk factor for cardiovascular disease.Patients with severe and very severe hypertriglyceridemia, defined as triglyceride levels of >1,000 mg/dl, should be considered to be at risk for pancreatitis.Patients with hypertriglyceridemia should undergo evaluation for secondary causes of hyperlipidemia, such as endocrine conditions and medications, and treatment should be focused on such secondary causes.Patients with primary hypertriglyceridemia should be assessed for a family history of dyslipidemia and cardiovascular disease, as well as for other cardiovascular risk factors including central obesity, hypertension, abnormalities of glucose metabolism and liver dysfunction.For patients with moderate hypertriglyceridemia, the treatment goal should be a non-high-density lipoprotein cholesterol level in agreement with NCEP-ATP guidelines.For patients with mild-to-moderate hypertriglyceridemia, first-line therapy should be lifestyle interventions including physical activity. A combination of diet modification and pharmacotherapy may also be considered.For patients with moderate-to-severe hypertriglyceridemia, treatment with fibrates niacin and/or omega-3 fatty acids alone or in combination with statins should be considered.A fibrate should be used as a first-line agent in patients with severe or very severe hypertriglyceridemia, in addition to reduction of dietary fat and simple carbohydrate intake.Statins should not be used as monotherapy for severe or very severe hypertriglyceridemia, but they may be useful for the treatment of moderate hypertriglyceridemia when indicated to modify cardiovascular risk.

The guideline is published in the September 2012 issue of Journal of Clinical Endocrinology and Metabolism.

246 IndianJournalofClinicalPractice, Vol. 23, No. 5, October 2012

*Assistant Professor, Dept. of Gastroenterology **Assistant Professor, Dept. of PharmacologyPt. BD Sharma, Postgraduate Institute of Medical Sciences, Rohtak, HaryanaAddressforcorrespondenceDr Garima BhutaniH. no. 517, Sector 15-A, Hisar, HaryanaE-mail: [email protected]

A Critical Insight into the Present and Upcoming Pharmacological Therapies for Treatment of GERDVIVekA*,gArImABhutAnI**

Gastroesophageal reflux disease (GERD) is defined as “a condition which develops when the reflux of gastric contents into the

esophagus causes troublesome symptoms (at least two heartburn episodes/week) and/or complications”.1 It has a prevalence rate of 10-30% and an annual incidence of 0.38-0.45% in the western world.2 The typical symptoms include heartburn, acid eructation and water brash. Other atypical symptoms could be cough, chest pain or hoarseness. Recurrent pulmonary aspiration may cause or aggravate chronic bronchitis, asthma, pulmonary fibrosis, chronic obstructive pulmonary disease or pneumonia. Chronic sinusitis and dental decay have also been ascribed to GERD. Esophagus-related complications include esophagitis, stricture, Barrett’s esophagus and adenocarcinoma. Of particular concern is the rising incidence of esophageal adenocarcinoma, an epidemiologic trend that parallels the increasing incidence of GERD. There were about 8,000 incident cases of esophageal adenocarcinoma in the United States in 2010 (half of all esophageal cancers); it is estimated that this disease burden has increased 2- to 6-fold in the last 20 years.3

AbstrAct

Gastroesophageal reflux disease (GERD) is a very common health problem of the society. Various pharmacological therapies are presently being used for the treatment of this condition. But these therapies are not able to relieve the symptoms in all groups of patients. So, there is a continuous need for newer drugs for the better management of GERD patients. Various drugs with novel mechanisms of action are being developed that target various factors involved in the pathophysiology of GERD. This article aims to achieve a critical insight into the presently available and the upcoming therapies for the treatment of GERD.

keywords:Gastroesophageal reflux disease, proton pump inhibitors, transient lower esophageal sphincter relaxations, potassium-competitive acid blockers

PAthoPhysiology

The pathophysiology of GERD identifies three major underlying mechanisms, including: i) The noxious effect exerted by the gastric refluxate (i.e. acid, pepsin and bile) on the esophageal mucosa; ii) a defective clearance of the refluxed contents as a result of impaired esophageal motility and iii) abnormalities of the antireflux mechanisms, mainly related to lower esophageal sphincter (LES) dysfunction. Not only gastric acid, but pepsin, bile and pancreatic enzymes within gastric secretions can also injure the esophageal epithelium.

The normal antireflux mechanisms consist of the LES, the crural diaphragm and the anatomical location of the gastroesophageal junction below the diaphragmatic hiatus. Reflux occurs only when the gradient of pressure between the LES and the stomach is lost. It can be caused by a sustained or transient decrease in LES tone. A sustained hypotension of the LES may be due to muscle weakness that could be either primary or secondary.4 Reflux mainly occurs during prolonged relaxations of the LES not related to swallowing, now referred to as transient LES relaxations (TLESRs).5 Apart from incompetent barriers, gastric contents are most likely to reflux when gastric volume is increased (after meals, in pyloric obstruction, in gastric stasis, during acid hypersecretion states) when gastric contents are near the gastroesophageal junction (in recumbency, bending down, hiatal hernia), and when gastric pressure is increased (obesity, pregnancy, ascites, tight clothes).

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MAnAgeMent

The goals of treatment are to provide symptom relief, heal erosive esophagitis and prevent complications. The options include lifestyle modifications, medical and nonmedical (antireflux surgery) management. Lifestyle modifications include reducing weight, sleeping with the head of the bed elevated by about 4-6 inches and elimination of factors that increase abdominal pressure. Patients should not smoke, should avoid consuming fatty foods, coffee, chocolate, alcohol, mint, orange juice, certain medications (such as anticholinergic drugs, calcium channel blockers and other smooth-muscle relaxants) and should also avoid ingesting large quantities of fluids with meals.

The treatment of GERD has been revolutionized by the advent of proton pump inhibitors (PPIs). Other drug options include H2 receptor antagonists (H2RAs), antacids and sodium alginate. Use of prokinetic drugs for GERD management has declined.

UnMet needs of Present therAPies

The cornerstone of medical treatment for GERD are the PPIs. They are presently preferred over histamine H2RAs and antacids in relieving GERD-related symptoms, healing and maintaining remission of erosive esophagitis and improving health-related quality-of-life. Despite this success, there is still a substantial subclass of patients (upto 40% in some studies) who do not completely respond symptomatically to a standard dose of PPIs.6 Upto 40% of adult patients with nonerosive reflux disease (NERD) remain symptomatic while on standard dose (once-daily) of PPIs.7 Treatment of extraesophageal manifestations of GERD has also been very disappointing.8 It has been suggested that nonresponders to once-daily PPI treatment should be qualified as PPI failure since there are at present no GERD-related Food and Drug Administration (FDA) indications for twice-daily dosing of PPIs.9 The failure of PPIs may be due to problems with compliance to therapy, TLESRs, sensitivity to weakly acidic and/or alkaline reflux, large volume of reflux and esophageal hypersensitivity.10 Another limitation associated with PPIs is that they take time to start working. They require several days to achieve maximum suppression of acid production, which is a disadvantage if the drugs are needed for intermittent or short-term use only when symptoms occur. The presently used PPIs have a short half-life. So, some recovery of acid secretion occurs during the course of the

day. It has also been argued that there is an association between long-term PPI treatment and nosocomial and community-acquired pneumonia,11 Clostridium difficile colitis,12 microscopic colitis13 and bacterial overgrowth.14 An association between long-term PPI consumption and increased risk for osteoporosis- related spine, wrist and hip fracture has also been hypothesized.15 In addition, it has been suggested that vitamins, minerals and electrolyte deficiencies, rebound acid secretion and gastric polyps may all result from chronic PPI treatment.15-19 H2RAs although are effective in controlling basal acid secretion, they are found to be less effective in suppressing postprandial acid secretion. They are good for treating mild-to-moderate erosive esophagitis, but not severe forms of the disease.20 The drugs counteract the night-time histamine-driven surge of gastric acid secretion and thus are popularly used at bedtime by patients who continue to be symptomatic on standard- or double-dose PPI therapy.21 However, tachyphylaxis develops quickly with H2RAs, limiting their regular use in clinical practice.22 They are mainly used as on-demand therapy. Antacids offer short- term symptomatic relief but neither alter esophageal acid clearance nor gastric acid secretion. The use of prokinetics as a treatment of GERD is also not preferred nowadays because they possess their own spectrum of side effects and low clinical impact.

Thus, there is a continuous need for new drugs for the better management of GERD patients. There is also a need for new therapeutic strategies reducing not only acid but also nonacidic reflux. Newer drugs under this class are known as ‘reflux inhibitors.’ Other newer drugs are also being developed with the aim of reducing increased esophageal perception.

This review aims at providing a critical insight into the upcoming agents under both acid suppressing and nonacid suppressing strategies for the pharmacological management of GERD.

recent AdVAnces in Acid sUPPression strAtegy

Based on the assumption that better reduction in acid secretion leads to better clinical outcome, several efforts have been made to develop newer drugs or formulations, which are intended to provide faster, better and more prolonged suppression of acid secretion.

Newer acid suppressing agents are:New formulations of existing PPIsNew PPIs

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Drugs with novel mechanism of acid suppression: Potassium-competitive acid blockers (P-CABs)

new forMUlAtions of existing PPis

dexlansoprazole Mr

Dexlansoprazole is the (R)-enantiomer of lansoprazole. Dexlansoprazole MR is a novel dual delayed-release formulation of dexlansoprazole approved by the FDA for the treatment of acid-related disorders. This formulation consists of two different types of granules, each with a different pH-dependent dissolution profile. One type of granules releases the drug in the duodenum and yields a fast peak, whereas the rest of the drug is released in the distal part of the small intestine by the other type of granules. The latter is responsible for a later but more sustained peak prolonging the half-life to six hours instead of three hours for the conventional preparation.23,24 Pharmacokinetic study of dexlansoprazole MR reveals two distinct peaks in the plasma concentration and a prolonged drug exposure during the 24-hour dosing interval. Better gastric acid suppression and improved efficacy in healing erosive esophagitis has been seen with dexlansoprazole MR as compared to lansoprazole in clinical studies.25,26

new PPis

tenatoprazole and s-tenatoprazole-na

Tenatoprazole is an imidazopyridine. It has a much slower metabolism than omeprazole, lansoprazole and rabeprazole, giving a plasma half-life of about six hours and thus provides longer inhibition of gastric acid secretion. This drug is seen to be more effective during night-time as compared to esomeprazole due to its longer duration of action.27 The sodium-salt of the S-enantiomer of tenatoprazole, S-tenatoprazole-Na (STN) is presently in clinical development. A meta-analysis of individual participant data (n = 121) from four similar pharmacodynamic studies confirmed the dose-dependent acid inhibitory effect and STN 60 mg once in the morning showed a significantly higher 24 hours median pH and 24-hour percentage of time pH >4 than esomeprazole 40 mg, attributed to the nocturnal difference.28 Thus, STN could provide greater clinical efficacy compared with current PPIs for patients in whom once-daily therapy is ineffective and those who need effective and prolonged nocturnal gastric acid inhibition.

Alevium (Agn201904-Z)

This compound is a prodrug form of omeprazole that provides a longer plasma dwell time because it is slowly absorbed throughout the small intestine and not just in the duodenum. It gets rapidly hydrolyzed in the blood to omeprazole and sulfonic acid.29 A single oral dose provides continued metered absorption (CMA) to prolong the plasma residence time, thus increasing the duration that activated proton pumps are exposed to the drug. A significantly greater and more prolonged acid suppression and better nocturnal acid suppression is achieved with alevium as compared to esomeprazole 40 mg/day in clinical studies.30,31 The substitution of the benzimidazole nitrogens confers acid stability to this compound and therefore, it does not require enteric coating.29

PotAssiUM-coMPetitiVe Acid blockers

P-CABs or acid pump antagonists inhibit gastric H+/K+-ATPase in a K+-competitive and reversible manner. Gastric H+K+-ATPase requires K+ in exchange for H+ to allow acid secretion in the canaliculus. Therefore, drugs interacting with the binding of K+ ions to the proton pump are expected to inhibit acid secretion.32 P-CABs reach therapeutic levels extremely quickly within the acidic environment of the parietal cell and canaliculus, which is advantageous for symptom relief. Studies have repeatedly demonstrated that they achieve full clinical effect within one dose and maintain similar effectiveness after several repeated doses.33 Thus, they offer quick and effective pain relief in patients.

SCH28080 was the first P-CAB to be investigated in clinical trials but the trials were terminated prematurely due to severe hepatotoxicity associated with the drug.34 AZD0865 (linaprazan) is another P-CAB that provides a faster onset of acid inhibition with a dose-dependent duration of activity, but no clinical benefit with once-daily administration has been shown over esomeprazole in clinical trials.32,35 However, increasing the frequency of administration of AZD0865 to twice-daily would be expected to outperform the currently approved PPIs. A reversible raise in transaminases was reported in some patients treated with AZD0865 also.34 Other P-CABs that are being studied in clinical trials are soraprazan (BY359) and TAK-438.36,37 P-CABs work on reducing acid, which unfortunately does not seem to be the main problem in PPI responders; this class of medications does nothing for TLESRs. It is possible that P-CABs could one day be used for bridging therapy (because of its fast-onset of activity) when starting PPIs

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until plasma concentrations of PPIs are high enough to be effective.34

tlesr redUcers

The LES and crural diaphragm normally protect the esophagus from acidic gastric contents.38 Stomach distension from the food bolus causes gastric wall mechanoreceptor activation, which subsequently triggers a vasovagal response. This reflex causes relaxation of both the LES and crural diaphragm. Sometimes, this mechanism, known as TLESRs, allows unintended gastric air and/or acidic gastric contents to reflux into the esophagus and causes the undesired irritation found in GERD. Several proposed new classes of GERD therapy focus upon this TLESR mechanism. The identification of pharmacologic receptors on the neural pathways mediating TLESR has opened the opportunity for the development of drugs that inhibit them and thereby gastroesophageal reflux. Several agents have been identified to reduce the triggering of TLESR, including cholecystokinin (CCK)-A antagonists, anticholinergic agents, nitric oxide (NO) synthase inhibitors, serotonin type 3 5HT3 inhibitors, morphine, somatostatin, N-methyl D-aspartate (NMDA) antagonists and cannabinoid receptor agonists.

gAbAb Agonists

Gama-aminobutyric acid (GABAB) agonists are probably the most promising emerging target for the treatment of GERD. GABA is an important inhibitory neurotransmitter in the central nervous system (CNS). It is abundantly present in the medullary centers controlling swallowing, esophageal motility and respiration. Activation of peripheral GABAB receptors inhibits gastric vagal mechanoreceptors and impairs vagal motor outflow, contributing to the inhibitory effect on the triggering of TLESRs.39 Baclofen, a GABAB receptor agonist clinically used in the management of spasticity, was reported to reduce TLESRs and reflux events in animals, healthy volunteers and GERD patients.40 Baclofen is seen to effectively reduce duodenal reflux and associated PPI-resistant symptoms.41 But, baclofen is associated with central side effects such as dizziness and somnolence compromising its clinical use. In an attempt to overcome these limitations several analogs are being developed.

Arbaclofen Placarbil

Arbaclofen placarbil (XP19986) is a prodrug of the R-isomer (the active stereoisomer) of baclofen that significantly reduced the number of reflux events in

GERD patients until 12 hours after dosing in early clinical trials. It also significantly reduced the number of GERD-related heartburn episodes in patients who had previously been on PPI therapy.42,43 Arbaclofen has a favorable tolerability and safety profile, with no significant differences compared with placebo. But recently, the development of arbaclofen placarbil has been halted due to lack of clinical efficacy in a phase 2B trial.44

lesogaberan (AZd3355)

Lesogaberan is a novel GABAB agonist that penetrates the CNS only at high serum levels. It is an effective inhibitor of transient relaxations and is well-tolerated.45 It is seen to produce a convincing but only modest symptom response compared to placebo in reflux disease patients, who have responded inadequately to PPI therapy.46 Hence, further development of this drug is halted due to low efficacy.44

mglur5 receptor Antagonists

Glutamate is vital for the transmission of vagal afferents to neurons in the brain that seem to be involved in triggering TLESRs. So antagonists of mGluR5 are being tried for inhibition of TLESRs and reflux episodes ADX10059 is a negative allosteric modulator of mGluR5, which is seen to decrease esophageal acid exposure in a proof of concept study in reflux disease patients. But, this drug was seen to be associated with a high rate of CNS side effects.47 To overcome this limitation, ADX10059 modified-release (MR) formulation was developed and a recent clinical trial confirmed its efficacy in reducing the esophageal acid exposure and postprandial weakly acidic reflux events in a group of healthy volunteers and GERD patients. But, liver toxicity still limits its clinical use for GERD treatment.48,49 Other mGluR5, antagonists, which are currently under evaluation include AZD2516 and AFQ056.

cb1 receptor Agonists and Antagonists

Two types of cannabinoid receptors are present in the human body, the cannabinoid receptor 1 (CBR1) and cannabinoid receptor 2 (CBR2). CBR1 has been localized in the NTS (nucleus tractus solitarius) and DMV (dorsal motor nucleus of the vagus) areas that are associated with central modulation of TLESRs.50 A mixed CBR1/CBR2 agonist delta 9- tetrahydrocannabinol (D9-THC) is seen to reduce the occurrence of meal-induced TLESRs in healthy subjects, but is associated with central side effects including nausea and vomiting.51

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Surprisingly, rimonabant, a CBR1 antagonist, was also shown to increase LES basal pressure, decrease the rate of postprandial TLESRs and, as a result, decrease postprandial reflux events in healthy volunteers. However, the drug has also fallen into disrepute due to central side effects.52 Taken together, the CBR1 is probably a less attractive target for GERD treatment.

cholecystokinin receptor Antagonists

CCK is released by endocrine duodenal and jejunal mucosa T cells, especially in response to a variety of fat nutrients, and its secretion is associated with gallbladder contraction, pancreatic enzyme secretion, inhibition of gastric emptying, fall in LES pressure and rise in TLESR frequency.53 Two CCK receptor subtypes (CCK-1 and CCK-2) have been characterized in the alimentary canal. Antagonists of both of these receptors have been tried in clinical trials. CCK is seen to exert a direct excitatory effect on human isolated LOS circular muscle by activating muscular CCK-1 receptors. Loxiglumide, a CCK-1 receptor antagonist is seen to significantly reduce postprandial TLESRs without significantly affecting LES pressure and fundic tone as compared with placebo in healthy volunteers. Deloxiglumide is the D-enantiomer of loxiglumide and the intravenous administration of this compound is seen to inhibit the CCK-mediated delay in gastric emptying, which might have a beneficial effect on the treatment of gastroesophageal reflux.54 The exact status and safety issues of this class of drugs would be made clear once the results of other clinical studies are available. Z360 and itriglumide are CCK-2 antagonists that are presently in clinical trials for treatment of GERD. However, there is much concern about the potential for tolerance to this drug class which unfortunately has been seen in drug trials.55 Hence, they are not likely to emerge as a good therapeutic options for patients of GERD.

5-ht3 receptor Agonist

Pumosetrag (DDP733) is a partial 5-HT3 receptor agonist with gastrointestinal prokinetic activities. Pumosetrag is seen to increase` LES basal pressure in experimental animal models. It also significantly reduced the rate of reflux events and increased the mean amplitude of the distal esophageal contractions without changing the LES basal pressure in healthy volunteers.56 It is presently being studied in phase II clinical trials. More clinical trials would be required for establishment of their role in the treatment of GERD patients.

nitric oxide synthase inhibitors

Nitrenergic neurones are part of the intrinsic inhibitory pathways innervating the LES, where NO is the major postganglionic inhibitory neurotransmitter regulating TLESRs. Preclinical studies have demonstrated a decrease in the rate of TLESRs produced by blockade of NO receptors.57 NG-monomethyl-L-arginine (L-NMMA), a specific NO synthesis blocker, is seen to significantly reduce the rate of TLESRs induced by gastric distension.58 The rate of TLESRs in the postprandial period also reduced by 25%.59 The therapeutic potential of L-NMMA in GERD treatment has still to be determined.

opioid receptor Agonists

Opioid-containing nerves are present in the myenteric plexus of human LES, and opioid receptors are widely distributed in nerves supplying the gut and the CNS. One of the main mechanisms of opioid µ-receptor agonists (e.g. morphine) is to suppress neuronal excitability both in the central and peripheral (including enteric) nervous systems.60 Morphine is seen to possess an inhibitory effect on the rate of TLESRs in GERD patients and to a lesser extent in healthy subjects and this effect is seen to be antagonized by naloxone.61 In spite of their effectiveness in reducing TLESRs, side effects like addiction and constipation seem to become the major hurdle in the development of morphine as a potential drug for the treatment of GERD.

recent AdVAnces in decreAsing esoPhAgeAl sensitiVity

Antagonists of trPV1

Transient receptor potential vanilloid 1 (TRPV1) channel is present in many parts of the body on nerve endings and it senses acidity and is sensitive for capsaicin, the pungent component of red pepper. TRPV1 receptors are present in mouth and esophagus, and it is thought to be one of the ways to sense upcoming acid and other noxious stimuli such as heat or distention. Blockers of this receptor have the potential to decrease sensitivity to reflux acid, but it can also block less acidic reflux sensations.62 AZD1386, a new TRPV1 antagonist, was demonstrated to reduce the threshold of esophageal pain perception in healthy men.63 Hence, this class of drugs may emerge as pain modulators in the GERD patients if their efficacy and safety is established in clinical trials.

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other targets

Other receptors that have been implicated in the sensitivity of the esophagus are tachykinins, which are a group of substances that include substance P. Blockers of tachykinins could also theoretically decrease the sensitivity of the esophagus, but this possibility has only recently been considered and requires further research. There have also been several proof-of-concept or proof-of-principle studies for motilin receptor agonists and ghrelin receptor agonists. However, for these targets, research is still in infancy.62

Antigastrin Vaccine

Antigastrin 17 vaccine is an immunoconjugate consisting of the nine NH2-terminal amino acids of human gastrin 17 (the B-cell epitope) linked to a large carrier protein-diphtheria toxoid. After administration, it stimulates the production of high affinity, gastrin 17-neutralizing antibodies that recognize both amidated gastrin 17 and glycine-extended gastrin 17.64 Animal data suggest that this antigastrin vaccine may have a future role as an acid-reducing agent.65 It is now being studied in clinical trials for the establishment of safety and efficacy. It is being expected that an immunogenic response to gastrin producing G cells would allow reliable acid suppression, while allowing hypergastrinemia, which is a common side effect of PPI treatment.

conclUsions

Various therapies are presently available for the treatment of GERD, but PPIs form the cornerstone of the treatment. Nowadays, there has been a growing concern regarding the limitations of the present therapies, both with respect to their limited efficacy and safety. Unmet needs of the present day therapies have led to extensive research into other newer drugs and drug targets. Some of the drugs like P-CABs and newer PPIs that are being developed which the aim of improving the acid suppression seem to be very promising therapies in near future. A reduction in the TLESRs is another potential mechanism, which is thought to provide benefit in resistant cases. Various drugs with different mechanisms of action are under development, which targets the reflux due to TLESRs. What the future holds for them would be made clearer in further clinical trials. Few others like antagonists of TRPV1, motilin receptor agonists and ghrelin receptor agonists work by decreasing the esophageal sensitivity. But for these pain modulators, research is still in infancy.

references

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*Head, Dept. of Pharmacy Practice**PharmD Intern†Principal, RIPER, Anantapur, Andhra Pradesh‡Head, Dept. of Infectious Diseases, RDT Hospital, Bathalapalli, Andhra PradeshAddressforcorrespondenceDr Dixon ThomasHead, Dept. of Pharmacy Practice Raghavendra Institute of Pharmaceutical Education and Research (RIPER)Chiyyedu Post, Anantapur - 515 721, Andhra PradeshE-mail: [email protected]

Is Essential Medicine Concept for Voluntary Organizations Only?

dIxonthomAs*,gseethArAm**,YPAdmAnABhAreddY†,gerArdoAlVArez-urIA‡

Charitable and voluntary organizations play a significant role in practicing essential medicine concept, which serves majority of the world

population.1

Formularies are short profiles of drugs that are preferred by a health plan or administration. The level of cost minimization needs to be studied for the compliance of prescribing from the hospital formulary.2

As medicines consume a significant portion of the hospital budget, the administration takes extra care in its handling. Two simple strategies are to prepare essential medicines list (EML) and reduce cost of medicines or invest higher capital on medicines for higher profit.3 In those health systems who have a EML and a good purchase policy, patients are charged much less for drugs than the marginal cost to the provider.4

who essentiAl Medicines list

The World Health Organization (WHO) promoted the concept of essential drugs. The concept of essential

AbstrAct

Patients are not aware that there is an essential list for medicines and what are its advantages. It is rare to see any patient ask for medicines from the essential medicines list (EML). Moreover, patients may have concerns about the quality and efficacy of the medicines, which are of low cost. EML is largely a deal of stakeholders in healthcare. Mostly, charities or voluntary organizations are developing or maintaining EML. For the rest of the world, medicines are a mode of increasing the revenue. In many parts of the world, corporate hospitals have a significant share in disseminating healthcare. EML is a tool for effective healthcare for voluntary organizations that believe in reducing the cost of medicines and make the resources available for more those who need at low budgets.

keywords:Essential medicines list, cost, healthcare, WHO, evidence

drugs started in the year 1997, with publication of the first list. Since, then WHO revises the model EML every two years.5 Recently, WHO intimated to use EML instead of essential drug list (EDL).6 According to the WHO, essential medicines are those that satisfy the priority healthcare needs of the population.7 The medicines included in the WHO model list of essential Medicines are selected with regard to disease prevalence, evidence of safety and efficacy and comparative cost-effectiveness.8 A visibly transparent and difficult process, which is done by a team of experts who critically analyze the available evidence and give to the process, their expertise and experience on evaluating published studies.9 Orphan medicines model list is used to complement the WHO list of essential medicines. These are the medicines for rare diseases.10,11

As costs of medicines change over time, the price of a medicine is not a reason to exclude it from the WHO model list if it meets the other stated selection criteria. Cost-effectiveness comparisons are made between alternative medicines within the same therapeutic group. Applications for inclusion, changes or deletions to the model list are submitted to the secretary of the Expert Committee for the Selection and use of essential medicines.8,12

indiAn essentiAl drUg list

The state of India’s healthcare is growing at a rapid pace. Healthcare cost as a percentage of the gross

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domestic product (GDP) is 5.1% and is designated as a priority for the government. Healthcare spending is expected to increase from $21 billion in 2005 to $45 billion in 2012. Public spending is anticipated to grow from the present amount of 0.9% of the GDP to 2% of the GDP by 2009. India carries a mixed disease burden of infectious diseases; re-emergence of diseases like tuberculosis and malaria; dreaded diseases like cancer and acquired immunodeficiency syndrome (AIDS) and lifestyle diseases like cardiovascular (CV), diabetes and depression. Disease burdens are projected to rise rapidly with 60% of the global CV burden by 2020 and 73 million diabetic patients by 2025. The changing disease profile therefore calls for more advanced and innovative therapies.13

While considering the drug procurement system, the Tamil Nadu Medical Services Corporation (TNMSC), which was set up in 1994 is a global benchmark for cost-effective drug procurement and distribution.14

Formularies/Essential drug lists can be useful tools in managing hospitals more rationally as they:15

Provide impartial drug informationPromote the appropriate use of safe, effective and good quality medicines.Support cost-effective utilization of drug budgets and improve access.

It is surprising that the Government of India, Ministry of Health and Family Welfare is not very keen on updating the EML. After 2003, the list was updated only in 2011.9

Campaigning to improve rational use of medicines through EDLs would be important. Governments should pay extra attention to this approach as medicines are important in regulating the national budget and health of people.16

Use of National List of Essential Medicines (NLEM) is expected to improve prescribing practices as well as the health outcomes. The appropriate use of medicines selected in the NLEM promotes rational use of medicines. Such rational use of medicines, especially antimicrobial drugs, reduces development of drug resistance. NLEM serves as a tool for public education and training of healthcare providers.15

Since the 1970s, many developing countries have started national programs for essential drugs to promote the availability, accessibility, affordability, quality and rational use of medicines.5

The implementation of the concept of essential medicines is intended to be flexible and adaptable to many different situations; exactly which medicines are regarded as essential remains a national responsibility.7

An essential medicine has been suggested as a strong indicator of the effectiveness of health systems and there should be clear relationships between the national EML, standard treatment guidelines and procurement practices within the country.17

The concepts of evidence-based selection of medicines and cost-effective treatment protocols need to be included in the training of doctors, pharmacists, nurses and other healthcare professionals. Pharmacovigilance remains an important aspect of ensuring the safety of medicine used.18

In India, each prescriber decides on his/her own, which make or brand is to be written for the patient. The information currently given to the patients in India does not make them informed enough to make a considered choice in selecting their medicines.19

The concept of essential medicines is relatively new to India and Tamil Nadu is the first state to develop the EML as early as in 1994. Then Government of Delhi too had developed its own list. The Government of India and many other individual states have their own EML. Unfortunately, the list is not regularly updated except for Tamil Nadu. The policy’s main objective is to improve the availability and accessibility of quality essential drugs for all those in need.20

other coUntries

In Australia, formularies mainly aim to “recognize the importance of world-class life-enhancing drugs to patients”, protect patients from higher costs and get better value from market competition between medicines with multiple brands.21

A report of the regional meeting about the role of education in essential use of medicines in Bangkok, Thailand, expressed the need to improve the use of medicines globally. It has been estimated by WHO that about half of all medicines are inappropriately prescribed, dispensed and sold and about half of all patients fail to take their medicines properly.22

In the health objectives of the National Drug Policy, the Government of South Africa clearly outlines its commitment to ensuring availability and accessibility of medicines for all people. These are as follows:

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To ensure the availability and accessibility of essential medicines to all citizens.To ensure the safety, efficacy and quality of drugs.To ensure good prescribing and dispensing practices.To promote the rational use of drugs by prescribers, dispensers and patients, through provision of the necessary training, education and information.To promote the concept of individual responsibility for health, preventive care and informed decision-making.18

Today, four out of every five countries, i.e., at least 156 countries in total, have adopted national EMLs. National lists are widely used for public procurement systems, reimbursement schemes, training, public education and other nation’s health.12

clinicAl PhArMAcy

There are lot of community outreach programs by the modern hospitals. Pharmacists should move from behind the counter and start serving the public by providing care instead of just dispensing. There is no future in the mere act of dispensing as the roles are expanding and the consumers expect more. With the emergence of automation, dispensing can and will be taken over by internet, machines, etc. Pharmacists have to fit into their new role as a member of the healthcare team. There is also a need for improvement in the dispensing service. Patients should feel the technical quality of the service.23

Continuity of care, equitable access and quality and safety are major foci in health services management. The introduction of clinical pharmacy services optimize medication management, improve continuity of patient care and improve patient access to medication.24

Clinical pharmacy interventions are vital parts in advanced health systems such as those in Europe, the United States or Australia (e.g., for the better healthcare management with medicines) and may produce a major improvement in a nation’s healthcare needs.25

Medicines are a special type of commodity where the user/consumer does not have the freedom to decide what to buy and at what cost. The doctor prescribes the items, the patients pay, buy and use.19

PhArMAceUticAl cAre

Outcomes-based formularies consider the clinical, economic and health-related quality-of-life (HRQoL) aspects of medication treatment.26

“Pharmaceutical care is the responsible provision of drug therapy for the purpose of achieving definite outcomes that improve a patient’s quality-of-life”. The concept of the seven-star pharmacist, introduced by WHO and taken-up by FIP in 2000 in its policy statement on Good Pharmacy Education Practice, sees the pharmacist as a caregiver, communicator, decision-maker, teacher, life-long learner, leader and manager. Pharmacists already in practice were mainly educated on the basis of the old paradigm of pharmaceutical product focus. If these pharmacists are to contribute effectively to the new patient-centered pharmaceutical practice, they must have the opportunity to acquire the new knowledge and skills required for their new role. To do this they must become life-long learners, one of the roles of the new pharmacist.27

eVidence-bAsed Medicine (clinicAl gUidelines/stAndArd treAtMent gUidelines)

It is not compulsory that all the medicines used in the hospital should be in the hospital EML. EML/Formulary is a continually revised compilation of pharmaceuticals (plus important ancillary information) that reflects the current clinical judgment of medical staff. Availability of brands or generics varied from single to many based on purchase policy. The drugs to be avoided or used with caution in renal failure, hepatic failure and in pregnancy were categorized and included in the formulary as additional information. The prepared hospital formulary needs to be periodically updated, which could thereby help as a tool to promote rational drug use.27

Applications for inclusion, changes or deletions to the model list are submitted to the secretary of the Expert Committee for the selection and use of essential medicines. The Expert Committee is responsible for reviewing the evidence provided in an application and deciding whether to include or delete a medicine.8

Listing of drugs in the EDL is determined by their clinical efficacy and their relative safety, including adverse drug reactions, side effects, interactions, the potential for errors and the risk of patient harm.1

Newly approved pharmaceutical, biological and vaccine products should be subjected to a rigorous clinical review and periodic re-review, based on evidence from the clinical literature. Evidence-based assessment of product efficacy, safety, effectiveness, and cost-effectiveness provide the foundation for such a review.12

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Evidence-based national clinical guidelines as the basis for training and rational prescribing; and a national medicines policy to balance conflicting policy objectives and to express government commitment to a common goal serve as cornerstone for national programs for essential drugs to promote rational use of medicines.5

The main reason for developing a hospital formulary is to set standards for best practice. This should promote high quality, evidence-based prescribing and reduce variation in the level of treatment provided to patients. A formulary can be used as a tool to rationalize the range of medicines used in standard practice.27

conclUsion

The WHO EML remains the most accepted list of priority medicines for most of the populations of the world. From the model list, different countries and healthcare settings prepare their EML. But it is of higher interest for voluntary organizations and hospitals for serving more number of people with minimal cost. The EML is highly evidence-based and there is considerable compromise on quality in many countries. Clinical pharmacists along with other healthcare professionals provide pharmaceutical care and support rational use of medicines (RUM). EML is a vital component in RUM and it is a multi-professional approach.

references

Grissinger M. The Truth about Hospital Formularies, Part 1: We’ve Come a Long Way-or Have We? P T 2008;33(8):441. Huskamp HA, Epstein AM, Blumenthal D. The impact of a national prescription drug formulary on prices, market share, and spending: lessons for Medicare? Health Aff (Millwood) 2003;22(3):149-58.Martin DK, Hollenberg D, MacRae S, Madden S, Singer P. Priority setting in a hospital drug formulary: a qualitative case study and evaluation. Health Policy 2003;66(3): 295-303.Olmstead T, Zeckhause R. The menu-setting problem and subsidized prices: drug formulary illustration. March 12, 1999. Available at: http://www.hks.harvard.edu/mrcbg/research/r.zeckhauser_jhe_menu.setting.problem.pdf (Accessed on 18/9/2011).Hogerzeil HV. The concept of essential medicines: lessons for rich countries. BMJ 2004;329(7475):1169-72.Laing R, Tisocki K, Ball DE. How to develop a national formulary based on the WHO model formulary: A practical Guide. WHO, Geneva, 2004. Available at: http://apps.who.int/medicinedocs/en/d/Js6171e (Accessed on 18/9/2011).

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All India Drug Action Network. Towards a people oriented, rational, drug policy! Nov. 2011. Available at: http://aidanindia.wordpress.com/2008/08/12/essential-drugs/ (Accessed on 29/08/2011).WHO Media Center and Information. Available at: http://www.who.int/mediacentre/factsheets/fs325/en/index.html (Accessed on 25/08/2011).B Gitanjali. The national essential medicines list of India: Time to revise and purge the mistakes. J Pharmacol Pharmacother 2010;1(2):73-74. E-drug. Definition Essential Drugs, Orphan Medicines List. Available at: http://www.essentialdrugs.org/edrug/archive/200609/msg00010.php (Accessed on 25/08/2011).Reidenberg MM. Are drugs for rare diseases “essential”? Bull World Health Organ 2006;84(9):686.Essential Medicines List. Available at: http://www.allcountries.org/health/essential_medicines_list_eml.html (Accessed on 25/08/2011).Kochhar P, Suvarna V, Duttagupta S, Sarkar S. Cost-effectiveness study comparing cefoperazone-sulbactam to a three-drug combination for treating intraabdominal infections in an Indian health-care setting. Value Health 2008;11 Suppl 1:S33-8.Manimekalai P, Zeena J. Facilitating rational drug usage: an illustrative example. March 2011. Available at: http://www.ictph.org.in/downloads/Facilitating%20Rational%20Drug%20Usage_with%20Appendix.pdf (Accessed on 18/9/2011).CDSCO. National List of Essential Medicines India, 2011. Available at: http://cdsco.nic.in/National%20List%20of%20Essential%20Medicine-%20final%20copy.pdf (Accessed on 18/9/2011).Hettihewa LM, Jayarathna KAKT. Comparison of the knowledge in core policies of essential drug list among medical practitioners and medical students in Galle, Sri Lanka. Online J Health Allied Sci 2010;9(3):7.Robertson J, Hill SR. The essential medicines list for a global patient population. Clin Pharmacol Ther 2007;82(5):498-500.Standard treatment guidelines and essential drug list for South Africa. 2006; Available at: http://www.kznhealth.gov.za/edladult06.pdf (Accessed on 05/09/2011).Veena R, Revikumar KG, Manna PK, Mohanta GP. Emerging trends in medicine procurement in government sector in India: a critical study. Int J Res Pharm Sci 2010;1(3): 372-81.Kar SS, Pradhan HS, Mohanta GP. Concept of essential medicines and rational use in public health. Indian J Community Med 2010;35(1):10-3.Lofgren H, Faunce T. Drug price reforms. Available at www.australianprescriber.com (Accessed on 25/08/2011).The Role of Education in Rational Use of Medicine. Report of the regional meeting. WHO; 2007:p.12-14. Available

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at: http://www.searo.who.int/LinkFiles/Meetings_SEA_DRUGS_157.pdf (Accessed on 25/08/2011).Wiedenmayer K, Summers RS, Mackie CA, Gous AGS, Everard M. Developing pharmacy practice: a focus on patient care. WHO, 2006. Available at: http://www.fip.org/files/fip/publications/DevelopingPharmacyPractice/DevelopingPharmacyPracticeEN.pdf (Accessed on 12/08/2011).Emmerton L, Marriott J, Bessell T, Nissen L, Dean L. Pharmacists and prescribing rights: review of international developments. J Pharm Pharm Sci 2005;8(2):217-25.

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Nissen L. Current status of pharmacist influences on prescribing of medicines. Am J Health Syst Pharm 2009;66(5 Suppl 3):S29-34.Wu WK, Sause RB, Zacker C. Use of health-related quality of life information in managed care formulary decision-making. Res Social Adm Pharm 2005;1(4): 579-98.D’Almeida RJ, Acharya LD, Rao PG, Jose J, Bhat RY. Development of hospital formulary for a tertiary care teaching hospital in south India. Indian J Pharm Sci 2007; 69(6):773-9.

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Keracnyl® in the Management of AcnePkhAndePArkAr*,rChAVdA**,VdurosIer**,QmukAddAm*,rkhArkAr†

AbstrAct

Objectives: To evaluate the utility of topical application of Keracnyl® cream in the treatment of mild-to-moderate acne in real life situations. Material and Methods: Patients (male and female) with clinical diagnosis of mild-to-moderate acne and without severe cystic lesions or nodules were enrolled. In the study and were instructed to apply Keracnyl® cream either alone or with topical anti-acne medications. The cream contains alpha-hydroxy acids (AHAs), Myrtacine® and Sabal serrulata (Keracnyl® cream) as an adjunctive to topical anti-acne medications in the treatment of mild-to-moderate grades of acne. The patients were assessed at baseline and at follow-up visit after eight weeks. Primary efficacy assessments were clinical improvement and secondary efficacy assessments were global efficacy and subjective and quality-of-life assessment at end of eight weeks. Results: The clinical improvement using modified Physician Visual Analog Scale (PVAS), showed moderate to marked improvement in 65.86% of acne patients at the end of eight weeks. The Investigators Global Assessment (IGA) showed that there was a significant decrease in the severity of acne, this decrease was maximum in the group of patients whose acne was graded as almost absent from 10% of patients at baseline to 40.69% at follow-up. The Global Acne Grading System (GAGS) assessment demonstrated a significant reduction in the overall severity of acne in all the zones. A mean change of –37.5% in seborrhea severity was noted at the end of treatment. Majority of the patients (>90%) were satisfied with the cosmetic qualities of Keracnyl® cream. Few patients had mild side effects (dry skin as the most frequent, 9.18%), but most of which resolved over continued application and none of the patients needed discontinuation of therapy due to local adverse events. About 90.69% of patients opined that Keracnyl® cream was efficacious and 99.6% of the patients demonstrated good tolerability. Conclusions: The dermocosmetic cream containing Myrtacine® (Keracnyl® cream) is effective and safe with cosmetic qualities to be used as monotherapy and as an adjunct to antiacne medications in treatment of mild-to-moderate acne vulgaris.

keywords:Acne, Myrtacine, IGA, GAGs, dermocosmetic

Acne vulgaris is a common dermatological disorder of the pilosebaceous unit presenting usually at puberty.1 Although acne is not

physically disabling, its psychological impact can be striking, contributing to lower self-esteem, depression and anxiety.2-4 As a result, there is a significant demand for effective acne therapies. It is characterized by the formation of open and closed comedones (noninflammatory lesions), papules, pustules and nodulocystic lesions (inflammatory lesions) generally affecting the face, arms and back. The pathogenesis is complex and multifactorial, which includes abnormal sebum production, follicular hyperkeratinization, bacterial proliferation and inflammation.5 The treatment goals are directed to reduce activity of the

sebaceous glands, normalize follicular proliferation, reduce bacterial colonization and control inflammation. Therefore, topical comedolytics, antibacterials and retinoids are mainly used for mild-to-moderate and severe acne. Systemic therapy with antibacterials, retinoids and hormones are mainly indicated for severe cases.6 Although effective, these therapies are associated with significant adverse effects. Retinoids have teratogenic potential. Antibiotics, as in most cases of infection, are associated with the problem of resistance, and therefore, therapeutic failure.

Keracnyl® topical cream is especially designed to manage patients with a tendency for acne, alone, in combination or in continuum to topical or oral anti-acne therapies. Its active ingredients are alpha-hydroxy acids (AHAs), Myrtacine® and Sabal serrulata. It has keratolytic, antiproliferative, antibacterial (against Propionibacterium acnes) and anti-inflammatory effects.

Myrtacine® is the active extract obtained from Myrtle, Myrtus communis L., which is a Mediterranean shrub, the leaves of which are known since times immemorial for their antiseptic and anti-inflammatory properties.7 Myrtacine® has shown purifying, keratoreducing

*Medical Service Division, Abbott Health Care, Mumbai**Medical Service Division, PFDC, France†Principal Doctor, Dr Kharkar Clinic, MumbaiAddressforcorrespondenceDr Prashant KhandeparkarChief Manager- Medical Services, Abbott Healthcare Pvt. Ltd.1st Floor, D-Mart Bldg, Goregaon Mulund Link Road, Mulund (W)E-mail: [email protected]

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properties (on P. acnes) and particularly rewarding anti-irritant in managing acne vulgaris. AHAs have been used in the management of acne since many years. They have shown promise both as topical creams8,9 as well as chemical peels.10,11 S. serrulata obtained as odor-free extract (by Pierre Fabre Phytochemical Research) from the fruits, which look like small dates of a small American palm tree, Sabal, which has been described in literature as possessing antiseborrheic properties, used in the management of acne.

The current study is a postmarketing surveillance study. It is a questionnaire-based observational study to evaluate the utility of Keracnyl® cream in the treatment of mild-to-moderate acne in real life situations.

objectiVe

To evaluate the utility of Keracnyl® cream in the treatment of acne under actual conditions of use.

MAteriAl And Methods

The current study was a prospective, observational study conducted by practicing dermatologists all over India.

Patients presenting with mild-to-moderate acne, for which the doctor had prescribed Keracnyl® cream were included in the study. Patients who were not willing to participate, those with severe acne and who were not likely to be observant during the observational period were excluded from the study. Additionally, patients with a known allergy to any of ingredients of Keracnyl® cream, those being treated with oral isotretinoin and pregnant/lactating women were excluded.

The patients included by the dermatologists were reviewed during a follow-up visit, eight weeks after the initial visit, when they were included in the study.

The assessments were carried out by clinicians as well as by patients. Assessment by clinicians included Investigator’s Global Assessment (IGA), Global Acne Grading System (GAGS), evolution of patients’ acne and effects of Keracnyl®. For the IGA, acne severity was assessed by clinician on a five point scale (0-4):

Absent: No retention lesion or residual inflammatory, hyperpigmentation and/or erythema possibleAlmost absent: Some blackheads and some tiny papulesSlight/Mild: Easily recognizable; less than half the face is affected with a few blackheads, papules and pustules

Moderate: More than half the face is affected with numerous blackheads, papules and pustules; a nodule may be presentSevere: The whole face is affected, covered with blackheads, various papules and pustules with some nodules and cysts.

The local and overall assessment of severity of acne was assessed by GAGS, where each of the five zones on face were listed separately from 0 to 4 (0: No lesion, 1: At least one blackhead, 2: At least one papule, 3: At least one pustule and 4: At least one nodule). The assessments were done for the following regions: (i) Forehead (ii) right cheek (iii) left cheek (iv) nose (v) chin and (vi) neck, chest and upper back. Evolution of patients’ acne was assessed based on the overall progress of the patients’ clinical response. Assessment of effects of Keracnyl® was done on the basis of questions related to overall efficacy, side effects, patient compliance and level of patient satisfaction. Self-assessment by patients was done by a self-assessment questionnaire with eight questions to be responded on a visual scale. The impact on quality-of-life was assessed by the Cardiff Acne Disability Index (CADI), with five questions to be answered by the patients. The evolution of acne in patients was assessed based on the question “From the beginning of your treatment with Keracnyl®, how do you assess the progress of your acne?” Patients’ satisfaction of therapy was assessed based on questions on efficacy, tolerance, unwanted effects and cosmetic qualities at the end of two months. All adverse events (AEs) and serious adverse events (SAEs) were considered for safety analysis.

Measurement data were expressed as means with one standard deviation. Discrete data were expressed as numbers with proportions. Ranking data for IGA were expressed as numbers and percentages. Mean scores were estimated for IGA, GAGS, self-assessment questionnaire and specific quality-of-life questionnaire at baseline and after therapy. Mean change and percent change in scores from baseline were calculated. Baseline scores for IGA, GAGS, self-assessment questionnaire and specific quality-of-life questionnaire were compared with post-treatment scores for any difference using Wilcoxon’s test. Comparison of IGA at baseline versus post-treatment was done using Chi-square test. All testing was done using two-sided tests at alpha 0.05.

resUlts

A total of 61 dermatologists, recruited five patients each, who fulfilled the inclusion criteria. A total of 305 patients were enrolled in the study out of which

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Table 1. Demographic and Baseline CharacteristicsNumber Percentage (%)

GenderMale 95 31.15 Female 210 68.85 Positive family history 150 49.18 Age groups ≤19 years 97 31.80 20-29 years 182 59.67 ≥30 years 26 8.52

Mean SD Age (years) 21.92 5.33 Duration of illness (months) 9.62 18.58

290 patients completed the study and 15 patients were lost to follow-up. The demographic and baseline characteristics of the patients are shown in Table 1. The mean duration of treatment was for eight weeks and the frequency of application was twice-daily in 58% and once-daily in 42% of the population.

clinical efficacy of keracnyl® cream by Physicians

investigator’s global Assessment

The IGA showed that there was a significant decrease in the severity of acne (p < 0.0001). This decrease was maximum in the group of patients whose acne was graded as ‘almost absent’ from 10% of patients at baseline to 40.69% at follow-up (Fig. 1). The details of other therapeutic as well as cosmetic products used by patients in the past as well as during the study are elaborated in Figures 2 and 3. The usage of medications co-prescribed both specifically for acne lesions as well as those used for overall skin hygiene are shown in Figure 3. All the concomitant medications were very well-tolerated in all the patients and also improved the overall response of acne lesions, signifying the concomitant usage of Keracnyl® cream.

global Acne grading system Assessment

The GAGS demonstrated a significant reduction (p < 0.0001) in the local and overall severity of acne, which was observed in all the zones (forehead, right cheek, left cheek, nose, chin, chest and upperback); (Fig. 4). The percentage change from baseline across different zones ranged from 46.21 to 54.22.

seborrhea severity evaluation

In the current study, seborrhea severity was mild-to-moderate in 88.2%, absent in 3.28% and severe in 8.52% of patients as shown in Table 2. After treatment with Keracnyl®, there was a mean change of 37.5% (p < 0.0001) from baseline.

overall efficacy of keracnyl® in Acne improvement

Overall, significant efficacy was seen in all the efficacy parameters like IGA, GAG, seborrhea for acne improvement (Fig. 5).

evaluation of Acne using Modified Physician Visual Analog scale

On assessment of evolution of patients’ acne using modified Physician Visual Analog Scale (PVAS), 65.86% of patients showed moderate to marked improvement (Fig. 6).

Per

cent

age

(%)

Acne specific products

Not specific to acne

Lotion or cleansing gel

Dermatological bar

8070605040302010

0

70.1%

29.8%

59.2%

11.3%

Figure 3. Other products co-prescribed with Keracnyl® cream.

70605040302010

0Topical medication

Per

cent

age

(%) 56.1%

44.3%

62.3%

Oral medication Products dermo-cosmetiques

Figure 2. Types of prescriptions combined with Keracnyl® cream.

605040302010

0Baseline (n = 290) Follow-up (n = 290)

IGA (% of patients)

4.140.69

40.6948.97

8.970.69

38.2845.52

10.002.07

Absent Almost absent Slight/Mild Moderate Severe

Figure 1. IGA at baseline and follow-up.

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(% of patients, n = 290)

WorseningNo changeSlight improvementModerate improvementMarked improvement

88 (30.34%)

0 (0.00%)3 (1.03%)

40 (13.79%)

56 (19.31%)103 (35.52%)

Figure 6. Evolution of patients’ acne.

Table 2. Seborrhea Severity

Severity grade No. Percentage (%)

Absent 10 3.28

Slight/Mild 124 40.66

Moderate 145 47.54

Severe 26 8.52

Table 3. Side Effects during use of Keracnyl®Side effects No. Percentage (%) Redness 15 4.92 Discomfort 8 2.62 Pricking 13 4.26 Localized swelling 4 1.31 Feeling of dry skin 28 9.18 Stretching 8 2.62 Others 2 0.66 Total 78 25.57

About 94.83% of patients found Keracnyl® efficient to very efficient.

side effects

A total of 78 patients had mild side effects most of which resolved over continued application and did not require the patients to discontinue the treatment (Table 3). The drug was very well-tolerated, with no serious AEs.

therapy compliance

About 99.6% of the patients showed moderate to good compliance to treatment with the study drug.

evaluation of Acne by Patients using self-assessment Questionnaire

According to the scores of the self-assessment questionnaire answered by patients, there was a significant change compared to baseline (p < 0.0001). The decrease was maximum in the number of blisters (% change: –61.58%) and red pimples >5 mm in size (% change: –54.78%; Table 4).

Quality-of-life evaluation using cAdi

The quality-of-life also improved significantly, especially the effect on daily life, where the percentage change from baseline was 37.5% (p < 0.0001), as assessed by CADI (Fig. 7).

At baselineAt follow-up

2.5

2

1.5

1

0.5

0

Figure 7. Severity improvement by Cardiff Acne Disability Index (CADI).

1.97

1.4

n = 290–37.5%

0.890.42

1.400.64

1.270.68

2.131.13

2.161.11

1.740.88

Neck

Chin

Nose

0.0 0.5 1.0 1.5 2.0 2.5

Mean GAGS scoreBaseline (n = 290)Follow-up (n = 290)

Figure 4. Improvement of mean GAGS score.

Lt. cheek

Rt. cheek

Forehead

IGA GAGS Seborrhea

At baseline At follow-up

2.35

1.699.59

4.85

1.6

1

–28%–50.6%

–37.5%2.5

2

1.5

1

0.5

0

12

10

8

6

4

2

0

1.81.61.41.2

10.80.60.40.2

0

Figure 5. Significant decrease in all acne-severity evaluation parameters with Keracnyl® (p < 0.0001).

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tolerability evaluation by Patients using self-assessment Questionnaire

When the acne evolution was self-assessed by patients, it was improved in 127 patients, much and slightly improved in 80 and 59 of them, respectively; 15 patients found mild to no change. About nine of them reported total disappearance of lesions.

About 90.69% of patients opined that Keracnyl® cream was efficacious and 99.6% of the patients demonstrated good tolerability. Similar to the physicians, patients also reported dry skin as the most frequent side effect (n = 28; 9.18%). This was followed by pricking sensation (4.26%), redness (4.92%), stretching (2.62%), discomfort (2.62%) and others (0.66%). Most patients (>90%) were satisfied with the cosmetic qualities of Keracnyl®.

discUssion

Our study showed that Keracnyl® is efficacious and safe in the management of mild-to-moderate acne, as assessed by both physicians as well as patients. The active ingredients of Keracnyl®, AHA and Myrtacine® have demonstrated beneficial effects in the management of acne. The other ingredient, S. serrulata has been described in the literature as possessing valuable anti-seborrhea properties.

The IGA by the physicians showed that patients at baseline with an ‘almost absent’ rating were only 10% while after treatment with Keracnyl®, this percentage increased to 40.69. Evaluation of severity of acne using GAGS showed a significant decrease in the severity of acne, ranging from 46.21 to 54.22%. According to the physicians’ assessment of evolution of acne, about 65.86% of the patients showed a moderate-to-marked improvement. About 94.83% and 90.69% of

patients found this therapy efficient, when assessed by physicians and self-assessed by patients, respectively. On self-assessment by patients, there was a significant improvement in all acne-related parameters; of which the maximum change of 61.58% was seen in the number of blisters.

The findings of the present study are in line with other studies conducted using Keracnyl® in patients with acne. In a study by Mengeaud et al in patients with acne, after 56 days of treatment, there was a 60% mean reduction of papules and pustules in patients treated with Keracnyl® versus 49% in those treated with adapalene. There was a 52% reduction in comedones with Keracnyl® versus 31% with adapalene.12 In another study by Durosier et al, the lesion count had significantly decreased at any location (forehead, cheeks or chin) at Day 28 and Day 56: 69% decrease for retentional lesions at Day 56 (p < 0.001) and 68.8% decrease for inflammatory lesions at Day 56 (p < 0.001). Overall efficacy was judged significant by the investigator in 80% of the cases.13 In another study by the same group, the investigators considered the efficacy of Keracnyl® on the acne lesions as ‘satisfactory’ to ‘very satisfactory’ in 84% of the volunteers after six weeks of treatment.14

In the current study, seborrhea was mild-to-moderate in 88.2% of patients. After treatment with Keracnyl®, there was a mean change of –37.5% (p < 0.0001) from baseline. The study by Durosier et al demonstrated that at Day 28 and Day 56, the score of seborrhea had also significantly decreased (p < 0.001).13 Ambonati et al showed a significant decrease in the level of sebum at Day 14 with Keracnyl® and at Day 28 with reference product. When patients assessed seborrhea, 95% of them reported seborrhea normalization, with no significant difference between the Keracnyl® and Exfoliac® at six weeks.14

Table 4. Self-assessment Questionnaire Scores for Individual Questions (n = 290)questions Baseline Follow-up Change from baseline wilcoxon sign test

Mean SD Mean SD Mean change

% change z p

Overall acne severity 1.97 0.62 1.40 0.55 –0.57 –28.72 –10.92 <0.0001 Oily skin 1.62 0.72 0.96 0.58 –0.65 –40.37 –11.80 <0.0001 No. of blackheads 1.76 0.88 1.02 0.62 –0.75 –42.38 –11.16 <0.0001 Red pimples (<5 mm) 1.35 0.75 0.68 0.63 –0.67 –49.47 –11.85 <0.0001 Red pimples (>5 mm) 0.70 0.71 0.32 0.51 –0.38 –54.78 –8.75 <0.0001 No. of blisters 0.46 0.63 0.18 0.40 –0.28 –61.58 –7.42 <0.0001 No. of scabs 0.47 0.61 0.22 0.46 –0.24 –52.64 –6.55 <0.0001 % surface with acne 1.22 0.52 0.87 0.47 –0.35 –28.88 –8.74 <0.0001

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Most of the patients were satisfied or very satisfied with the cosmetic properties of Keracnyl®. Similar findings were seen in the study by Durosier et al, where cosmetic qualities of Keracnyl® was judged ‘satisfactory’ or ‘very satisfactory’ by the patients.13

In our study, Keracnyl® was very well-tolerated (99.6%) by the patients. Dryness of skin was the commonest side effect. Durosier demonstrated that overall tolerance was good or very good in 92% of the cases. In their study, erythema and desquamation had significantly decreased at Day 28 and Day 56 in comparison to Day 0 (p < 0.001). However, unlike in our study, no significant evolution of skin dryness was observed.14 When compared to retinoid cream, Keracnyl® induced lower frequency of dryness (p < 0.02 at Day 28 and 56) and scaling at Day 28. Both creams decreased the intensity of erythema similarly.12 In the study by Ambonati et al, no side effects were reported, and 100% of patients evaluated the safety as ‘good’ to ‘very good’.14

conclUsion

Our study shows that Keracnyl® is a safe and effective option for the management of mild-to-moderate acne. The main limitation of our study is that this was a single arm, open label study, with no comparator. Therefore, larger, multicentric, randomized trials would help to confirm these findings.

AcknowledgmentA Martin, A Padmawar, A Patwardhan, A Ramnani, A Sharma, A Singh, A Sood, Anupama, B Swarnkar, C Anand, Chitranjan, D Hemnani, D Hussain, D Patil, D Vohra, Devishetty, G Singh, I Williams, J Mathew, K Ajwani, K Bhagat, K Chhatwal, K Shah, M Ghala, M Gopal, M Lata, M Lohra, M Makhecha, M Prabhulkar, M Shetty, M Sogani, Nazia, P Aswani, P Desai, P Sharma, Padmavati, Parthiban, Praveen, R Dixit, R Khambhati, R Nair, R Pandhi, R Sampatkumar, R Upadhyay, Rathespillai, S Arora, S Dayani, S Kantawala, S Kumar, S Mala, S Salahuddin, S Sharma, S Tippanawar, T Narang, T Rao, Thilack, V Daniel, V Dave, V Pande, V Rao, V Sharma.

references

Gollnick H, Cunliffe W, Berson D, Dreno B, Finlay A, Leyden JJ, et al; Global Alliance to Improve Outcomes in Acne. Management of acne: a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol 2003;49(1 Suppl):S1-37. Klassen AF, Newton JN, Mallon E. Measuring quality

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of life in people referred for specialist care of acne: comparing generic and disease-specific measures. J Am Acad Dermatol 2000;43(2 Pt 1):229-33.Dalgard F, Gieler U, Holm JØ, Bjertness E, Hauser S. Self-esteem and body satisfaction among late adolescents with acne: results from a population survey. J Am Acad Dermatol 2008;59(5):746-51.Yazici K, Baz K, Yazici AE, Köktürk A, Tot S, Demirseren D, et al. Disease-specific quality of life is associated with anxiety and depression in patients with acne. J Eur Acad Dermatol Venereol 2004;18(4):435-9.Zaenglein AL, Graber EM, Thiboutot DM, Strauss JS. Acne vulgaris and acneiform eruption. In: Fitzpatrick’s Dermatology in General Medicine. 7th edition, Wolff K, et al (Eds.), McGraw Hill: New York 2008:p.687-703.Choudhury S, Chatterjee S, Sarkar DK, Dutta RN. Efficacy and safety of topical nadifloxacin and benzoyl peroxide versus clindamycin and benzoyl peroxide in acne vulgaris: A randomized controlled trial. Indian J Pharmacol 2011;43(6):628-31.Asif HM, Akram M, Shahab Uddin, et al. Myrtus communis Linn. (Pharmacological activity). J Med Plants Res 2011;5(26):6257-9.Baldo A, Bezzola P, Curatolo S, Florio T, Lo Guzzo G, Lo Presti M, et al. Efficacy of an alpha-hydroxy acid (AHA)-based cream, even in monotherapy, in patients with mild-moderate acne. G Ital Dermatol Venereol 2010;145(3):319-22.Abels C, Kaszuba A, Michalak I, Werdier D, Knie U, Kaszuba A. A 10% glycolic acid containing oil-in-water emulsion improves mild acne: a randomized double-blind placebo-controlled trial. J Cosmet Dermatol 2011;10(3):202-9. Kessler E, Flanagan K, Chia C, Rogers C, Glaser DA. Comparison of alpha- and beta-hydroxy acid chemical peels in the treatment of mild to moderately severe facial acne vulgaris. Dermatol Surg 2008;34(1):45-50; discussion 51.Briden ME. Alpha-hydroxyacid chemical peeling agents: case studies and rationale for safe and effective use. Cutis 2004;73(2 Suppl):18-24.Mengeaud V, Laverdet C, Schmitt AM, et al. A comparison of the efficacy and safety of AHA cream and cream containing a retinoid derivative in the treatment of acne vulgaris. Poster.Durosier V, Dunel C, Sibaud V, et al. Efficacy and tolerance of a cream containing polyhydroxy acids and Sabal serrulata extract on patients with moderate acne. Poster.Ambonati M, Sibaud V, Durosier V. Efficacy and safety evaluation of Keracnyl® cream versus a reference product in patients suffering from acne vulgaris. Les Nouvelles Dermatologiques 2007;26:105-6.

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*Professor**Assistant Professor†LecturerDept. of Obstetrics and Gynecology‡Assistant Professor, Dept. of AnesthesiaGSVM Medical College, Kanpur¶Assistant Professor, Dept. of AnesthesiaRama Medical College, Kanpur#Junior Resident, Dept. of Obstetrics and GynecologyGSVM Medical College, KanpurAddressforcorrespondenceDr Renu GuptaD-4, Doctors Block, GSVM Medical College, Kanpur - 208 002E-mail: [email protected]

Modulating Postoperative Pain Relief in Cesarean Section with Use of Transdermal Diclofenac PatchnguPtA*,rguPtA**,sAgArwAl†,AAgArwAl‡,snguPtA¶,VthAwAnI#

Today, relief of postoperative pain has become an indispensible component of our practice, as postoperative pain relief is associated

with attenuation of various respiratory circulatory metabolic and psychological complications. It seems obvious that unrelieved severe pain after surgery may have numerous undesirable effects, so pain relief in postoperative period is of immense importance.

objectiVe

To evaluate the safety and efficacy of transdermal diclofenac patch in comparison to intramuscular diclofenac on post cesarean pain.


A randomized prospective study, was conducted between July 2010 to April 2011 at Dept. of Obstetrics and Gynecology, GSVM Medical College, Kanpur. One hundred fifty women who underwent lower segment

AbstrAct

Objective: To evaluate the safety and efficacy of transdermal diclofenac patch in comparison to intramuscular diclofenac in post cesarean section pain. Study design: One hundred fifty women who had undergone cesarean section were included in the randomized prospective study. The study subjects were randomly assigned into two groups with similar demographic profile. Group A received transdermal diclofenac patch and Group B received intramuscular diclofenac. Analgesic effect was compared in both groups. Results: Transdermal diclofenac patch group had better pain relief; 77.33% women did not require any further analgesic, whereas in intramuscular diclofenac group, pain relief was not effective and all women required additional doses. Conclusion: Transdermal diclofenac patch is a newer, effective and convenient method of pain relief in post cesarean section pain.

keywords:Transdermal diclofenac patch, cesarean section, postoperative pain relief

cesarean section under spinal anesthesia were recruited for study after informed consent. Hemodynamic parameters, respiratory rate and duration of surgery were noted.

Women were randomly divided into two groups: Group A (n = 75) received diclofenac patch 100 mg (diclofenac diethylamine 50 cm2 in size) over the inner aspect of thigh immediately after surgery. Group B (n = 75) received injection diclofenac 75 mg intra-muscular (as routinely used in our hospital). Women with history of allergy to nonsteroidal anti- inflammatory drugs (NSAIDs), gastrointestinal (GI) ulcers, bleeding tendency, renal insufficiency, liver disorder, cerebrovascular accidents and receiving anticoagulants were excluded from study. Patients were observed for first 24 hours in postoperative period. The time when the women first reported moderate-to-severe pain (≥4 in visual analog scale [VAS]) at rest was noted; thereafter pain was assessed at 4, 8, 12, 16, 20 and 24 hours postoperatively using VAS. If the women reported their pain ≥4 at rest on 0-10 VAS, they were given repeat dose of analgesic. If this regimen did not relieve their pain, they received, injection pentazocine (30 mg) and promethazine (50 mg) intramuscularly. Patients were asked to grade their pain by pointing at a scale marked 0-10. VAS of ‘0’ was defined as no pain while ‘10’ was defined as worst pain imaginable.

Hemodynamic parameters at different time were noted in both groups and incidence of minor side effects like nausea, vomiting and itching at the site of application of patch or injection were also noted.

Dr SM Rajendran

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We also observed for development of any major side effects (neurological, cardiovascular, GI complications).

Subjective assessment was done to evaluate patient satisfaction with pain control. Women and observers were blinded to study. Double binding was done by chit in box technique for both the patient and observer. The results were analyzed using unpaired ‘t’ test and ‘Chi-square test’. P value of <0.05 was considered statistically significant.

resUlts

Patients of both groups were comparable in respect to age, height, weight and intraoperative characteristics (Table 1).

Majority of the women in Group A (n = 75) (77.33%), did not require any additional analgesic upto 24 hours. In postoperative period, rest of women (22.67%), complained of moderate-to-severe pain between 12-24 hours and required additional analgesia. While in Group B, 70.67% women complained of moderate-to-severe pain between 6-8 hours of surgery and required additional dose. 26.67% women complained of pain between 8-12 hours and rest 2.67% complained of pain

after 12 hours. Seven patients in this group also required injection pentazocine and promethazine (Table 2).

Postoperative hemodynamic parameters were similar in both groups. Incidence of nausea and vomiting was low and similar in both groups. Eight percent patients in Group A reported mild tolerable itching over the skin where patch was applied (Table 3). The patient subjective report of satisfaction with pain management was superior in Group A at 24 hours. Overall satisfaction with pain relief was 77.33% in Group A, while it was 48% in Group B (p < 0.05). Transdermal patch application was more convenient and satisfactory in comparison to intramuscular route (Table 4).

discUssion

The main aim of postoperative pain relief is to provide subjective comfort, in addition to inhibiting nociceptive impulses caused by surgical trauma and to blunt autonomic as well as somatic reflexes to pain subsequently, this will enhance restoration of function by allowing the patient to breath, cough and to be easily ambulant.

NSAIDs are effective in postoperative pain relief not only through peripheral action (inhibition of cyclo-oxygenase I and II) but also through central effects.1 There are few studies on uses of transdermal NSAIDs on postoperative pain relief.2,3

NSAIDs are very effective analgesics in postoperative pain, as shown in various studies.4-6 Diclofenac, an NSAID has very few side effects and good analgesic

Table 1. Demographic Profile

Parameter Group A (n = 75)

Group B (n = 75)

Remarks

Age (years) 23.6 ± 4.4 24.8 ± 3.4 p > 0.05

Weight (kg) 56.5 ± 4.6 58.2 ± 3.8 p > 0.05

Height (cm) 154.23 ± 12.5 154.2 ± 11.2 p > 0.05

Gravida primi/multi

40/35 42/33 p > 0.05

Data = Mean + SD.

Table 2. First Pain PerceptionTime at which women first complained of moderate-to-severe pain (postoperatively)

Group A (n = 75)

Group B (n = 75)

Remarks

Within 4 hours 0 04-8 hours 0 53 (70.67%)8-12 hours 0 20 (26.67%)12-16 hours 2 (2.67%) 2 (2.67%)16-20 hours 5 (6.67%) 020-24 hours 10 (13.33%) 0Total 17 (22.67%) 75 (100%) p < 0.0001

Table 3. Side EffectsParameter Group A

(n = 75)Group B (n = 75)

Remarks

Emesis 7 (09.3%) 10 (13.33%) p > 0.05

Pain at the site of injection

- 25 (33.33%)

Itching and hyperemia at patch site

6 (8.0%) -

Table 4. Subjective Satisfaction with Pain Management

Time Group A (n = 75)

Group B (n = 75)

Remarks

At 6 hours 70 (93.33%) 6 (8.0%) p < 0.0001

At 12 hours 65 (86.67%) 39 (52.0%) p < 0.003

At 24 hours 58 (77.33%) 36 (48.0%) p < 0.01

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effect, is a useful drug in treatment of various pain disorders.7

Our study showed that transdermal diclofenac patch application in postoperative period after cesarean section had very good analgesic effect. It reduced the need for further analgesia in immediate postoperative period (upto 24 hours) and was devoid of any sedative action. Use of opioids in postoperative analgesia in post lower segment cesarean section patient may produce drowsiness in postoperative period, which can delay initiation of breastfeeding.

Patients were also very much satisfied with this mode of application. There were no major side effects; minor ailments like nausea, vomiting were not increased. Transdermal patch did not produce any skin reaction at application site, while intramuscular diclofenac injection produced pain at site of injection.

conclUsion

The study concluded that application of transdermal diclofenac patch is very effective and safe method in post cesarean pain relief. As it also decreases the need for further analgesic so, it is more cost-effective while it’s subjective satisfaction and convenience was immense and incomparable to any route of analgesia.

references

Jurna I, Brune K. Central effect of the non-steroid anti-inflammatory agents, indomethacin, ibuprofen, and diclofenac, determined in C fibre-evoked activity in single neurones of the rat thalamus. Pain 1990;41(1):71-80.Liu K, Chia YY, Lo Y, Kan YY, Wang JJ, Ho ST. Effect of preoperative transdermal ketoprofen on post hysterectomy pain. Zhonghua Yi Xue Za Zhi (Taipei) 1997;60(6):290-5.Saha SP, Bhattacharjee N, Biswas SC, Roy SCG, Halder M, Barui G. Effect of transdermal Diclofenac patch on post caesarean section pain. Asian J Obs Gynae Pract 2009;1: 36-40.Sunshine A, Olson NZ. Analgesic efficacy of ketoprofen in postpartum, general surgery, and chronic cancer pain. J Clin Pharmacol 1988;28(12 Suppl):S47-54.Kinsella J, Moffat AC, Patrick JA, Prentice JW, McArdle CS, Kenny GN. Ketorolac trometamol for postoperative analgesia after orthopaedic surgery. Br J Anaesth 1992; 69(1):19-22.MCLintock TT, Kenny GN, Howie JC, McArdle CS, Lawrie S, Aitken H. Assessment of the analgesic efficacy of nefopan hydrochloride after upper abdominal surgery: a study using patient controlled analgesia. Br J Surg 1988;75(8):779-81.Moffat AC, Kenny GN, Prentice JW. Postoperative nefopam and diclofenac. Evaluation of their morphine-sparing effect after upper abdominal surgery. Anaesthesia 1990;45(4):302-5.

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*Professor and Head**Senior ResidentDept. of Medicine, Assam Medical College and HospitalDibrugarh, Assam

Study of the Prevalence and Clinical Profile of Diabetes in the Urban Population of DibrugarhrkkotokeY*,ABulkAlAmAzAdPk**,hImAnABJYotIdAs**,AneeshAshok**,kAmAlrAJkhowA**,VIshukumAr**,trIdIPkumArdAs**

Diabetes mellitus (DM) constitutes a growing concern to the population of the world, predominantly because of the devastating

effects of its chronic complications. The development of certain complications during the course of this ‘lifelong’ disease is so common that some of them have been regarded as ‘consequences’ rather than complications. Major long-term complications of diabetes include nephropathy, retinopathy, neuropathy and coronary artery disease (CAD). There are 2-6 fold-increased risk of thromboembolic strokes in diabetics than in non-diabetic population, and stroke-related mortality and morbidity are increasing in the diabetic population. The prevalence of diabetes is rapidly rising all over the globe at an alarming rate. Over the past 30 years, the status of diabetes has changed from being considered as a mild disorder of the elderly into one of the major causes of morbidity and mortality affecting the youth and the middle-aged. The global burden of DM is enormous as estimated by World Health Organization (WHO) recently. The prevalence of diabetes among adult population worldwide will be 300 million by the year 2025 and it is presumed that majority of

AbstrAct

Objective: To find out prevalence of diabetes mellitus in urban population of Dibrugarh and to study their clinical profile. Material and methods: A cross-sectional study was done, where 730 people from 3 wards in three corners of Dibrugarh town were included by systemic random sampling. They were interviewed with the help of structured questionnaire and evaluated with clinical examination and minor laboratory tests. Result and observations: The prevalence of diabetes mellitus was found to be 12.6%; the prevalence of type 1 was found to be 0.41% and 12.19% were type 2. There was a gradual increase in prevalence with increasing age and a clear male preponderance in all age groups. Most of the diabetic patients were found to be overweight (51.09%). The prevalence of impaired glucose tolerance (IGT) was found to be 8.78% and that of hypertension was 69.57%. Among various complications, the most common were found to be neuropathy (39.96%), followed by retinopathy (32.61%), nephropathy (30.43%), cataract (23.91%), coronary artery disease (CAD) (14.13%) and foot ulcer (9.78%).

keywords:Diabetes mellitus, coronary artery disease, body mass index, impaired glucose tolerance

the burden will be in the developing countries like India, China, etc. It is also thought that India will have the maximum burden from 23 million in 2003 to 57 million in 2025. Hence, it is appropriate that the knowledge of prevalence of DM in different corners and section of the population of India be the urgent need of the hour so that awareness, lifestyle modification can be instituted to prevent the disease and its complications. As no methodical population-based study is yet published in this urban population of Dibrugarh, Upper Assam; the present study is trying to give a detailed picture of this problem.

AiMs And objectiVes

To study the prevalence of DM in the urban population of Dibrugarh town of Dibrugarh district.To study the clinical profile of DM patients of the said population.


The present study was conducted in the Dibrugarh town of Dibrugarh district, throughout a period of one year from August 2006 to July 2007. The Dibrugarh town consists of approximately 1,37,000 population. Considering the national prevalence of DM to be 12% and using standard biostatistical methods for

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calculation of sample size, a total of 730 subjects were studied from three different wards of Dibrugarh town.

calculation of sample size

N = 4pq/L2

= (4 × 12.1 × 88)/(0.2 × 12.1)

= 730p = Prevalence

q = 100-p

L = Acceptable error (20% of p)

case selection criteria

Inclusion criteriaSubjects with age >15 years from all sections (with or without DM) of the community including both male and female.Subjects residing in the Dibrugarh town of Dibrugarh district, Assam.Already diagnosed case of DM with complication.

Exclusion criteriaSubjects with age <15 years.Subjects residing in the nearby rural areas of Dibrugarh town.

Pregnant women.

Patient receiving steroid therapy, thiazides, phenytoin and other drugs, which alter blood sugar level.

resUlt And obserVAtions

Of the total 730 peoples, 92 (12.6%) were found to be diabetics, of which 63 (68.48%) were males and 29 (31.52%) were females. Two hundred seventy-four females were studied and 29 (10.58%) were found to be diabetic. Of the 456 male subjects, 63 (13.82%) were found to be diabetic. Out of 63 male diabetics, the highest prevalence 24 (38.10%) was in the age group of ≥65 years. Out of 29 female diabetics, the highest prevalence 11 (37.93%) was in the age group of 55-64 years (Table 1).

Among various complications, the most common was found to be neuropathy (36.96%), followed by retinopathy (32.61%), nephropathy (30.43%), cataract (23.91%), CAD (14.13%) and foot ulcer (9.78%). The prevalence of retinopathy, nephropathy and cataract were found more in females and CAD and foot ulcer in males (Table 2).

Table 1. Age Distribution of Diabetics in Both SexesAge group (in years) Male Female

Number of cases Percentage (%) Number of cases Percentage (%)15-24 1 1.59 0 025-34 2 3.17 0 035-44 7 11.11 4 13.7945-54 13 20.63 5 17.2455-64 16 25.40 11 37.93≥65 24 38.10 9 31.04Total 63 100.00 29 100.00

Table 2. Prevalence of Complications in Male and Female Diabetic PatientsComplication Total prevalence Prevalence

No. % Male diabetics Female diabeticsNo % No %

Neuropathy 34 36.96 21 33.33 10 44.83Retinopathy 30 32.61 17 26.98 13 44.83Nephropathy 28 30.43 18 28.57 10 34.48Cataract 22 23.91 14 22.22 8 27.59CAD 13 14.13 9 14.29 4 13.79Diabetic foot ulcer 9 9.78 7 11.11 2 6.89

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As regards symptomatology, out of the three diabetic patients in 25-34 age group, 2 (66.67%) complained of fatigue and all the three had hyperphagia. Six (54.55%) cases in the age group 35-44 years complained of polyphagia and severe fatigue. Out of the total 18 patients in the age group of 45-54 years, four (22.22%) had recent weight gain and neuropathic symptoms, 10 (55.56%) cases had severe fatigue and 14 (77.78%) patients had hyperphagia. Of the 27 cases of diabetes in the age group 55-64 years, 19 (70.37%) patients had fatigue and 13 (48.15%) patients complained of neuropathic symptoms and three (11.11%) had dizziness. Out of 33 diabetic patients who were ≥65 years, 27 (81.82%) had severe fatigue, 14 (51.52%) had neuropathic symptoms and 11 (33.33%) had dizziness. Of the total 92 diabetics, three (0.41%) were clinically diagnosed to have type 1 DM (T1DM) and all were male.

As regards signs of diabetic foot, of the total 11 patients in age group 35-44 years, two (18.18%) had skin hyper pigmentation. Of the 18 patients in the age group 45-54 years, two (11.11%) had callus in their feet, 3 (16.67%) had skin hyperpigmentation, one (5.56%) had foot ulcer and 3 (16.67%) had hair loss in their feet. Of the total 27 patients in the age group 55-64 years, six (22.22%) had callus in their feet, seven (25.93%) had skin hyperpigmentation, one (3.70%) had localized infections of the feet, two (7.4%) had foot ulcer, three (11.11%) had peripheral pulse abnormality and 11 (40.74%) had hair loss in their feet. Of the 33 patients, above the age of 65 years, 13 (39.39%) had callus in their feet, 11 (33.33%) had skin hyperpigmentation, nine (27.27%) had localized infections of the feet, six (18.18%) had foot ulcer, 11 (33.33%) had peripheral pulse abnormality and 17 (51.52%) had hair loss in their feet.

It was observed that 69.57% of diabetic patients were also hypertensive; 73.02% (46) male diabetics and 62.07% (18) female diabetics were hypertensive. Most of the diabetics were overweight (51.09%) and obese (27.17%), in comparison to the normal weight (11.96%) and lean (9.78%). Out of the remaining 638 nondiabetic subjects, 56 (8.78%) patients had impaired glucose tolerance (IGT). Of these, 34 (60.71%) were males and 22 (39.29%) were females.

discUssion

This study included 730 subjects selected from urban population of Dibrugarh town of Dibrugarh district during a period of one year from August 2006 to July 2007.

Prevalence of diabetes Mellitus

Out of total 730 subjects, 92 (12.6%) subjects were found to be diabetic. The prevalence of diabetes in urban dwellers has been observed to be in the range of 4-11.6%. Bai et al (1999) reported a prevalence of 17.4%. Raman Kutty et al (1999) reported a prevalence of 16.3%. Zargar (2000) reported prevalence of 14.23%. Mohan et al (2003) reported prevalence of 12% in urban population. Our study shows some variation probably due to the ethnic population present in this area, most likely Mongoloid origin.

sex distribution

Out of total 92 diabetic patients diagnosed, 63 (68.48%) were males and 29 (31.52%) were females showing gross male preponderance. Mohan et al (2003) in a study covering a larger group of 9,873 cases of type 2 DM (T2DM) observed 62.6% male and 37.4% female diabetics. The prevalence of DM in different sex observed in our study is comparable with the study conducted by Mohan et al.

Prevalence of t1dM

Out of the 92 diabetic patients, three (3.26%) were T1DM and remaining 89 (96.74%) were found to have T2DM. In Asia, the prevalence of T1DM was 9.7% of all diabetics in that region during the year 1998. In USA, T1DM accounts for approximately 5-10% of all cases of diabetes. So, the present study shows a lesser prevalence of T1DM in comparison to the studies conducted earlier in Asia and USA.

Prevalence of igt

Total prevalence of IGT among the study subjects was 8.78%. Ramachandran et al (2001) reported 14.4% prevalence of IGT amongst the study subjects. Our study shows a lesser prevalence of IGT compared to the previous study.

clinical Profile of diabetes among study Population

body Mass index

In our study, 47 (51.09%) out of 92 patients were overweight and nine (9.8%) were underweight. Joslin et al (1921) reported that 51% of males and 59% of female were obese. Das (1995) found that 23.9% of patients with T2DM were underweight. Our study shows higher prevalence of overweight and lesser prevalence of underweight compared to above studies. The ethnic population of this region being mostly nonvegetarian, may be responsible.

ClInICAlstudY


hypertension

Out of 92 diabetic patients, 64 (69.57%) were hypertensive. Of these, 46 (71.9%) were males and 18 (28.1%) were females. Chanda (1997) reported an overall prevalence of hypertension as 44.8% (38.9% males and 47.6% females). Therefore, the present study shows a higher prevalence of hypertension both in males and females.

neuropathy

The prevalence of neuropathy in our study was 36.96%. Das (1995) reported the prevalence to be 49.4%. Mohan et al (1991) found prevalence to be 44.6%. Dharamajan et al (1994) found prevalence to be 42%. Thus, our study shows lesser prevalence of neuropathy.

nephropathy

The prevalence of nephropathy in our study was 30.43%. Dharamajan et al (1994) found prevalence to be 6.3%. Thus, our study shows lesser prevalence of nephropathy but it was comparable with the data quoted in Davidson’s Textbook of Medicine (2006).

retinopathy

Prevalence of retinopathy in our study was 32.61%. Mohan et al (1991) reported the prevalence to be 44.09%. Dharamajan et al (1994) found prevalence to be 5.5%. So, we observe that the prevalence of retinopathy varies among different studies in different population groups.

foot ulcer

Prevalence of foot ulcer in our study was 9.78%, which is less when compared with the data (15%) quoted in Harrison’s Textbook of Medicine (2008).

coronary artery disease

Prevalence of CAD in our study was 14.13%. Nigam et al (1994) found the prevalence to be 10.2% and Mukhyaprana et al (2000) found the prevalence to be 2.7%. Thus, the results of our study are comparable.

cataract

Prevalence of cataract disease in our study was 23.91%. Das et al (1995) found the prevalence to be 15.4%. Thus, our study shows higher prevalence.

conclUsion

The present study was carried out to examine the prevalence of DM in urban population of Dibrugarh town of Dibrugarh district and its clinical profile.

The prevalence of DM in the study subjects was found to be 12.6% with gradual increase in the incidence of diabetes with increasing age with male preponderance in all age group. Most of the diabetics were in the overweight and obese group and a small number in the lean group and normal weight group. The prevalence of T1DM was 0.41% and all of them were males. The prevalence of IGT was 8.78% and hypertension was 69.75%, both with male preponderance.

Regarding the clinical profile it was found that prevalence of complications is higher in male diabetics. But when sex-specific prevalence was examined and it is seen that except CAD and foot ulcer, all other complications were more prevalent in female diabetics when compared to male counterparts. Among various complications, the most common was found to be neuropathy (39.96%), followed by retinopathy (32.61%) and nephropathy (30.43%), cataract (23.91%), CAD (14.13%), foot ulcer (9.78%). This is the first documented study conducted in the urban population of Dibrugarh of Dibrugarh district of Upper Assam.

AcknowledgmentWe are thankful to the Principal cum Chief Superintendent, Assam Medical College and Hospital for publishing the records.

sUggested reAding

Huizinga MM, Rothman RL. Addressing the diabetes pandemic: a comprehensive approach. Indian J Med Res 2006;124(5):481-4.Mohan V, Shanthirani S, Deepa R, Premalatha G, Sastry NG, Saroja R; Chennai Urban Population Study (CUPS No. 4). Intra-urban differences in the prevalence of the metabolic syndrome in southern India - the Chennai Urban Population Study (CUPS No. 4). Diabet Med 2001;18(4):280-7.WHO (1998). Prevention and Control of Diabetes Mellitus. Report of Inter Country Workshop, Dhaka, Bangladesh, April 1998;SEA/NCD/40:p.27-30.Bai PV, Krishnaswami CV, Chellamariappan M. Prevalence and incidence of type-2 diabetes and impaired glucose tolerance in a selected Indian urban population. J Assoc Physicians India 1999;47(11):1060-4.Raman Kutty V, Joseph A, Soman CR. High prevalence of type 2 diabetes in an urban settlement in Kerala, India. Ethn Health 1999;4(4):231-9.Zargar AH, Khan AK, Masoodi SR, Laway BA, Wani AI, Bashir MI, et al. Prevalence of type 2 diabetes mellitus and impaired glucose tolerance in the Kashmir Valley of the Indian subcontinent. Diabetes Res Clin Pract 2000;47(2):135-46.

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Mohan V, Shanthirani CS, Deepa R. Glucose intolerance (diabetes and IGT) in a selected South Indian population with special reference to family history, obesity and lifestyle factors - the Chennai Urban Population Study (CUPS 14). J Assoc Physicians India 2003;51:771-7.Park K. Epidemiology of chronic non-communicable diseases and condition. In: Park’s Textbook of Preventive and Social Medicine. 20th edition, Vol. 6, Banarsidas Bhanot: Jabalpur, India 2009:p.341-3.American Diabetes Association, Diabetes 2001, Vital Statistics Alexandria, VA, ADA 2001;24:454-9.Ramachandran A, Snehalatha C, Kapur A, Vijay V, Mohan V, Das AK, et al; Diabetes Epidemiology Study Group in India (DESI). High prevalence of diabetes and impaired glucose tolerance in India: National Urban Diabetes Survey. Diabetologia 2001;44(9):1094-101.Joslin EP. The prevention of diabetes mellitus. J Am Med Assoc 1921;76:79-84.Das S, Samal KC, Baliarsinha AK, Tripathy BB. Lean (underweight) NIDDM - peculiarities and differences in metabolic and hormonal status - a pilot study. J Assoc Physicians India 1995;43(5):339-42.Chadha SL, Gopinath N, Shekhawat S. Urban-rural differences in the prevalence of coronary heart disease

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and its risk factors in Delhi. Bull World Health Organ 1997;75(1):31-8.Das S. Lipid profiles-standards and interpretations. In: Proceedings of the Novo-Nordisk Diabetes Update 1995. Kapur A (Ed.) Health Care Communication, Bombay 1995:p.107-15.Mohan V, Alberti KGMM. Diabetes in Tropics. International Textbook of Diabetes Mellitus. 1991:p.177-96.Dharamajan P, Sundaram A, Madhavan R, Manjula N. Clinical Profile of NIDDM Subjects: Novo-Nardisk Diabetes Update 1994 Proceedings. Health Care Communications. 1994:p.105-7.Mukhyaprana P, Santhirani S, Deepa RJ, Markovitz J. Prevanlence and Risk factors of microvascular disease in a selected South Indian population. Diabetes Care 2000;23:1295-300.Harrison’s Principles of Internal Medicine. 17th edition, Volume 2, McGraw-Hill, New York, 2008;Chapter 338:p.2292.Davidson Principles and Practice of Medicine. 20th edition, 2006;Chapter 21:p.841.Nigam, Ahuja MMS, Rao PV. Vascular complication of diabetes mellitus. In: Endrocrinology Metabolism of Diabetes. Kochupillai N (Ed.), Volume 2, McMillan: Delhi 1994:p.33-8.

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*Associate Professor**Senior Resident, Dept. of Pediatrics†Associate Professor‡Tutor (PG Student), Dept. of PSM¶Pediatric Neurologist#NeurophysicianMedical College and SSG Hospital, VadodaraAddressforcorrespondenceDr Shwetal Bhatt12, Samruddhi Society, Bh. Avishkar Complex, Akota, VadodaraE-mail: [email protected]

Clinico-etiological and EEG Profile of Neonatal SeizuresshwetAlBhAtt*,nItArAJu**,suPrIYAPhAnse**,sAngItAVPAtel†,geetIkAmAdAn‡,sAnJeeVmehtA¶,ChetAntrIVedI#

Clinical seizures are defined as paroxysmal alteration in the neurological function i.e., behavioral, motor and/or autonomic function.

The incidence of seizures is highest during the neonatal period, but clinical diagnosis is often difficult, thereby making it difficult to estimate the true incidence of neonatal seizures. Seizures are often the first sign of neurological dysfunction in the newborn, but their clinical presentation is quite variable often presenting only as subtle seizures in the form of chewing, lip smacking, fluttering of eyelids, staring look, etc. Volpe1 has classified seizures into five clinical types, viz. subtle, multifocal clonic, focal clonic, generalized tonic and

AbstrAct

Background: Incidence of seizures is highest during the neonatal period, but clinical diagnosis is often difficult, thereby making it difficult to estimate the true incidence of neonatal seizures. Electroencephalography (EEG) provides a useful noninvasive test to diagnose neonatal seizures and evaluate degree of perinatal damage to brain and long-term prognosis. Aim: To evaluate the clinical, etiological and EEG profile of neonatal seizures. Material and methods: An observational study was carried out at tertiary care level neonatal intensive care units (NICUs) of SSG Hospital, Vadodara. A total of 172 newborns having seizures within first 28 days of life were enrolled. Baseline data was collected including antenatal history, perinatal history and evidence of HIE (hypoxic ischemic encephalopathy). Description of seizures, a complete examination and investigations including blood sugar, serum calcium, magnesium, electrolytes and treatment were also recorded. Due to financial constraints as well as general condition of the patients, it was possible to record EEGs in 50 newborns using neonatal montages as per guidelines of American EEG Society. Results: The incidence of seizures was 0.77% among term newborns and 1.1% among preterm newborns. HIE was the most common etiology (77%), while multifocal seizures (51%) were the most common presentation; 65.9% had easy to control seizures while 34% had difficult-to-control seizures requiring more than one drug. Of the total 50 EEGs done, 14 were abnormal; maximum being in HIE (57%) followed by mixed etiology (28.57%), hypocalcemia (7.14%) and pyogenic meningitis (7.14%). Conclusion: The overall incidence of neonatal seizures was found to be 0.77%, majority being preterm, low birth weight infants and within first 48 hours of life. EEG abnormalities were found in 28% of the recorded EEGs. HIE (77%) was the most common cause of neonatal seizures with EEG abnormalities.

keywords:Neonatal seizures, electroencephalography

myoclonic. Moreover, neonatal seizures are difficult to investigate and consequently determination of etiology and initiation of therapy may be delayed resulting in poor neurological outcome. Neonatal seizures can be due to various causes such as hypoxic-ischemic encephalopathy, intracranial hemorrhage (ICH), meningitis, hypoglycemia, hypocalcemia, congenital malformation, etc. Though electroencephalography (EEG) provides a useful noninvasive test to diagnose neonatal seizures and evaluate degree of perinatal damage to brain and long-term prognosis, yet its interpretation is influenced by variations in normal maturation process of brain.

AiM

To evaluate the correlation of EEG with clinical and etiological profile of neonatal seizures.


The study was conducted at the tertiary care level neonatal intensive care units (NICUs) of the Dept. of Pediatrics, SSG Hospital, Vadodara. Prior to beginning

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the study, ethical approval was taken from the local IECHR (Institutional Ethics Committee for Human Research), Medical College Baroda. The cohort consisted of neonates admitted in the NICUs (intramural and extramural) from September 2008 to November 2009. It was an observational study. A total of 172 neonates who either had seizures during the NICU stay or had seizures which were noticed by other doctors and referred from outside, were included in the study after written and informed consent of the parents.

Details of each baby with a complete antenatal and perinatal history including Apgar scores for intramural deliveries and history suggestive of birth asphyxia or examination revealing signs of hypoxic ischemic encephalopathy (HIE), were noted. A history of seizures associated with poor feeding, prolonged lethargy, recurrent vomiting, with family history of consanguinity and/or neonatal seizure with early fetal and neonatal death was taken to rule out inborn errors of metabolism. A complete description of the seizure, day of onset, duration and frequency was noted and classified according to Volpe. Vital signs, congenital malformation and cutaneous markers, were examined for and systemic examination was done. Neurological examination was done at the time of onset of seizures. Sarnat and Sarnat score was considered for HIE grading.

Investigations done included: Serum C-reactive protein, random blood sugar, packed cell volume, serum calcium, serum magnesium, serum sodium, blood urea, serum creatinine, serum bilirubin, blood culture and sensitivity, cerebrospinal fluid (CSF) examination, USG head, CT scan, MRI (wherever feasible and indicated) and EEG. All babies were treated using standard treatment protocol.

Once the neonate was hemodynamically stable and off intravenous fluids, he/she was sent for the EEG recording at the earliest. EEG was obtained on RMS EEG machine having 25 leads. EEG was done at a Neurophysian’s clinic and was read by a Pediatric neurophysician. The techniques used were as per guidelines of the American EEG Society for recording EEG in neonates. Neonatal montages were used and 16 leads were used as against the standard of 25 leads in the adult. Triclofos was used in the dose of 50 mg/kg/dose to induce sleep when required. Babies were also subjected to photic stimulation to provoke any abnormalities in brain activity. Each EEG recording was made for 30-40 minutes in order to bring out the sleep wake cycles in each neonate and read by a pediatric neurologist.

Statistical analysis: Data was recorded in a pretested detailed Proforma and entered in Microsoft Excel worksheet. Median and mean were used to analyze data that was distributed in the Gaussian manner.

resUlts

During the study period a total of 4,412 babies were admitted in the intramural NICU, and 1,900 were admitted in the extramural NICU. One hundred seventy-two newborns satisfying the inclusion criteria were enrolled in the study. The incidence of seizures was found to be 0.77% with 0.7% among term newborns and 1.1% among preterm newborns (Fig. 1). One hundred twenty-one males and 51 females were enrolled in the study and the male:female ratio was found to be 2.37:1. The incidence of seizures was found to be 2.8% among low birth weight and 0.88% among very low birth weight infants. Twenty-two percent of the newborns with neonatal seizures were found to be small for date (SFD). Eighty-one percent of the neonatal seizures were found to be early-onset (<48 hours of life)

Intramural Extramural

0.70% 0.70%

11.30%

1.10%

12

10

8

6

4

2

0

Per

cent

age

(%)

TermPreterm

Figure 1. Distribution of incidence of seizures.

HIE

908070605040302010

0

Per

cent

age

(%)

Figure 2. Distribution of various etiologies of neonatal seizures.

Hypoc

alcem

ia

Hypog

lycem

ia

Pyoge

nic m

ening

itis ICH

Bilirub

in en

ceph

alopa

thy

Electro

lyte i

mbalan

ce

Mixed c

ause

s

orIgInAlArtICle


Table 1. Babies with Abnormal EEGs in Various EtiologiesEtiology No. of

casesNo. of

babies with EEG done

No. of babies with abnormal

EEGsHIE 134 35 10 (28.57%)Hypocalcemia 15 9 3 (33.33%)Hypoglycemia 8 5 -Pyogenic meningitis

14 4 3 (75%)

ICH 6 2 1 (50%)Bilirubin encephalopathy

3 1 -

Electrolyte imbalance

9 7 2 (28.6%)

Mixed 15 11 4 (36.36%)Total 74* 23 (31%)

*Though the total number of EEGs done was 50, due to overlapping of some etiologies e.g. hypocalcemia and pyogenic meningitis, the total figure is >50.

Table 2. EEG Abnormalities in Various EtiologiesEEG HIE Hypocalcemia Hypoglycemia ICH Pyogenic

meningitisElectrolyte imbalance

Bilirubin enceph

Mixed causes

Background abnormalitiesLow voltage - - - - - - - -Lack of sleep patterns 1 2 - - 1 1 - 2Invariant delta activity 5 - - 1 1 1 - 2Immature for age 3 1 - - 1 - - -Dischargesa) Area of involvement

Generalized - - - - - - - -Multifocal 1 - - - - - - -Focal 1 - - - - - - -

b) Types of dischargesSpikes 2 - - - - - - -Sharp 1 - - - - - - -Both - - - - - - - -

with 90% of them attributable to HIE. The rest 19% were late-onset (>48 hours of life) with pyogenic meningitis contributing to 31% of them.

A total of 352 seizure episodes were noted in the 172 newborns, with a median onset of 38.5 hours for the first episode. Multifocal seizures (51%) were found to be the most common seizure type followed by subtle seizures (43%), tonic seizures (4.6%) and clonic seizures

(0.65). HIE (77.9%) was found to be the most common etiology of seizures, followed by hypocalcemia (8.7%), pyogenic meningitis (8.1%), mixed causes (8.7%), electrolyte imbalance (5.2%), hypoglycemia (4.65%), ICH (3.5%) and bilirubin encephalopathy (1.74%) (Fig. 2). About 65.9% patients had easy-to-control seizures while 34% had difficult-to-control seizures requiring more than one drug for seizure control.

Of the total 50 EEGs done, 36 (72%) were normal, while 14 (28%) were found to be abnormal (Table 1). On elaborating the etiologies found with the abnormal EEGs, 28.57% of EEGs were done in patients with HIE, 33.33% were done in patients with hypocalcemia, 75% were done in pyogenic meningitis, 50% were done in ICH, 28.57% were done in electrolyte imbalance and 36.36% of the EEGs were done in patients with mixed causes were found to be abnormal.

On interpreting the data in a different way, out of the total number of abnormal EEGs, HIE showed maximum abnormalities (57%), followed by mixed etiology (28.57%), hypocalcemia (7.14%) and pyogenic meningitis (7.14%).

Among the abnormalities found in the EEGs, background abnormalities were found in 22 EEGs, out of which 10 had invariant delta activity, seven had disorganized sleep pattern (Fig. 3) and five were immature for chronological age. One EEG had multifocal sharp wave discharges (Table 2). Of the 22 EEGs with background abnormalities, nine were due to HIE. And the one EEG with multifocal sharp waves was also found to be due

orIgInAlArtICle


to HIE (Table 2). Cranial ultrasound (CUS) was done in 39 patients, out of which 12 (31%) were found to be abnormal. Seven CUS showed dilatation of ventricles and three showed ICH. CT head could be done in four patients, out of which 2 patients had IVH with hydrocephalus, one had bilateral cerebral infarcts and the other had changes suggestive of HIE.

discUssion

Seizures in newborns are mostly identified by clinical observation. However, some of the clinically identified seizures are not accompanied by an EEG correlate and vice versa leading to an overestimation as well as underestimation of neonatal seizures, respectively. National Neonatal-Perinatal Database (NNPD) data report the incidence of neonatal seizures as 1% in intramural deliveries and 18% in the extramural neonates.2 In comparison, our study reported an incidence of 0.77% amongst intramural admissions and 7.3% amongst extramural admissions, respectively. The present study found an incidence of 0.7% in term babies and 1.1% in preterm babies among intramural admissions (Fig. 1), which is comparable to a previous study at SSG Hospital in 2000, which showed an incidence of 2% among preterms and 1.1% among term babies.

The male:female ratio among the enrolled newborns was 2.37:1, as compared to 2.46:1 in the hospital admissions. Comparable results were shown by Eghbalian et al3 with a ratio of 3:1, though NNPD 2002-2003 reported a ratio of 1.1:1 for intramural and 2.01:1 for extramural admissions.2 Low birth weight

is an important risk factor, as clinical seizures in low birth weight babies often indicate severe brain injury and are associated with serious morbidity and a high mortality risk.

The risk of neonatal seizures varies inversely with birth weight. In the present study, the incidence of seizures in low birth weight babies was 2.8% as compared to 6% as reported by Eghbalian et al3 and 1.5% reported by Kumar et al.4 The median age of onset of seizures in the present study was 38.5 hours in term babies and 19.5 hours in preterm babies, with an average of 2.03 seizure episodes per baby in the first 28 days of life. Early-onset seizures (within first 48 hours of life) were the commonest and contributed to 81% of the total seizures (Fig. 4). Similar findings were observed by Tekgul et al wherein 64% of neonatal seizures occurred within first 24 hours of life.5 Of the total 139 babies with early- onset seizures, 98 had onset within first 12 hours of life; of these, 90% were due to HIE. Therefore, vigilant monitoring and early recognition of seizures could contribute to decreasing morbidity and mortality in this group. Moreover, unlike older infants, neonates rarely have well-organized generalized tonic-clonic seizures. Premature infants have even less well-organized spells than full-term babies. In the present study, multifocal clonic seizures (51%) were the most common seizure type followed by subtle (43%), generalized tonic (4.6%) and focal clonic (0.6%). Kumar et al reported similar findings, with multifocal seizures being the most common presentation (42.4%).4 However, Mizrahi et al6 and Scher et al7 have reported subtle seizures as the most common type of neonatal seizures in their studies.

Figure 3. EEG showing disorganized sleep pattern in a full-term 2.3 kg vacuum delivered child with delayed cry.

Figure 4. EEG showing frequent spike and sharp waves in a full-term normal delivered baby with delayed cry with early-onset difficult-to-control seizures.

orIgInAlArtICle


Perinatal asphyxia is the most frequent cause of neonatal seizures (Fig. 2). In various studies, the reported incidence is 15-35%.8,9 But reports of higher incidence have been reported by Kumar et al4 (49%) and Nunes et al10 (51%). In the present study, perinatal asphyxia was the major contributing factor of neonatal seizures, contributing to 77.9% of the total seizures. EEG evidence of diffuse cerebral injury like burst suppression, dysmaturity, attenuation of background and electrical silence is seen in HIE and meningitis,10 but exact incidence of these findings has not been well-established. In the present study, out of 35 EEGs done in babies with HIE, 10 (28.57%) were abnormal (Table 1). Out of these, five showed invariant delta activity, three showed immature for age background abnormalities, while one showed abnormal sleep patterns (Table 2). Rose and Lombroso11 and Mizrahi and Kellaway6 reported abnormalities in standard EEG in HIE in 70% and 46.3%, respectively.

Hypocalcemia (8.7%) was the next most common cause of neonatal seizures in the present study (Fig. 2). In comparison, Kumar et al4 (24.7%) and Eghbalian et al3 (35.3%) have reported higher incidence. Hypocalcemia occurs more commonly in infants with trauma, hemolytic disease or asphyxia and may co-exist with HIE, hypoglycemia and hypomagnesemia.12 Early-onset hypocalcemia occurs in first 2-3 days of life. Of the 15 babies with hypocalcemic seizures, EEG was done in nine babies, out of which three (33.3%) babies had abnormalities on EEG (Table 1). Abnormal record in standard EEG in hypocalcemia has been reported in 34.4% by Keen and Lee13 and in 27.8% by Rose and Lombroso.12 Hypoglycemia is most frequent in low birth weight babies, most of them being small for gestational age and in infants of diabetic mothers. Incidence of hypoglycemia as reported in literature varies from 2 to 32.4%.9,14

Hypoglycemia contributed 4.65% of the total seizures in our present study. Seizures due to hypoglycemia typically occur on the second postnatal day.15 In neonatal hypoglycemic seizures, EEG produces multifocal discharges. However, in the present study, none of the EEGs showed any abnormality. EEGs were done in four of the 14 babies with meningitis, out of which three was abnormal with invariant delta activity in one, lack of sleep pattern in one and immature for age pattern in one. Abnormal standard EEGs in meningitis have also been reported in 33.3% cases by Rose and Lombroso 12 and 17% by Mizrahi and Kellaway.6

conclUsion

The overall incidence of neonatal seizures was found to be 0.77%, majority being preterm, low birth weight infants and within first 48 hours of life. EEG abnormalities were found in 28% of the recorded EEGs. HIE (77%) was the most common cause of neonatal seizures with EEG abnormalities.

references

Volpe J. Neonatal Seizures. N Engl J Med 1973;289(8):413-6.National Neonatal-Perinatal Database Report 2002-2003. National Neonatology Forum NNPD Network. January, 2005.Eghbalian F, Monsef A. Neonatal seizures: etiology and frequency. Iran J Child Neurol 2007;2(1):39-42.Kumar A, Gupta A, Talukdar B. Clinico-etiological and EEG profile of neonatal seizures. Indian J Pediatr 2007;74(1):33-7.Tekgul H, Gauvreau K, Soul J, Murphy L, Robertson R, Stewart J, et al. The current etiologic profile and neurodevelopmental outcome of seizures in term newborn infants. Pediatrics 2006;117(4):1270-80.Mizrahi EM, Kellaway P. Characterization and classification of neonatal seizures. Neurology 1987;37(12):1837-44.Scher MS, Aso K, Beggarly ME, Hamid MY, Steppe DA, Painter MJ. Electrographic seizures in preterm and full-term neonates: clinical correlates, associated brain lesions, and risk for neurologic sequelae. Pediatrics 1993;91(1): 128-34.Levene MI, Trounce JQ. Cause of neonatal convulsions. Towards more precise diagnosis. Arch Dis Child 1986;61(1):78-9.Goldberg HJ. Neonatal convulsions - a 10 year review. Arch Dis Child 1983;58(12):976-8.Nunes ML, Martins MP, Barea BM, Wainberg RC, Costa JC. Neurological outcome of newborns with neonatal seizures: a cohort study in a tertiary university hospital. Arq Neuropsiquiatr 2008;66(2A):168-74.Rose AL, Lombroso CT. A study of clinical, pathological, and electroencephalographic features in 137 full-term babies with a long-term follow-up. Pediatrics 1970;45(3):404-25. Taeusch WH, Ballard RA, Gleason CA (Eds.). Avery’s Diseases of the Newborn. 8th edition, Saunders 2004:p.1005-25.Keen JH, Lee D. Sequelae of neonatal convulsions. Study of 112 infants. Arch Dis Child 1973;48(7):542-6.Iype M, Prasad M, Nair PM, Geetha S, Kailas L. The newborn with seizures - a follow-up study. Indian Pediatr 2008;45(9):749-52.Volpe JJ, Neonatal seizures. In: Neurology of Newborn. 4th edition, Volpe JJ (Ed.), WB Saunders: Philadelphia 2001:p.178-214.

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Evaluation of a Case of Penetrating Ocular InjuryJItenderPhogAt*,VIVekgAgneJA**,sumItsAChdeVA*,mukeshrAthI†

AbstrAct

Ocular trauma is an important cause of visual loss and disability. It can be categorized as penetrating and nonpenetrating. Penetrating ocular injury may result in ocular damage of various degrees. With modern diagnostic techniques, surgical approaches and rehabilitation, many eyes can be salvaged with retention of vision. But penetrating ocular trauma is a complicated and challenging condition.

keywords:Globe rupture, intraocular foreign body, endophthalmitis

Ocular injuries are a frequent cause of unilateral visual loss. Children account for between 20% and 50% of all ocular injuries.1-3 It has

been estimated that 90% of all ocular injuries are preventable.4 Strategies for prevention require a knowledge of the cause of injury and hence may enable more appropriate targeting of resources towards prevention of such injuries. The etiology of pediatric ocular injuries is likely to differ from that of adult.

Injury was classified as penetrating injury in accordance with the Birmingham Eye Trauma Terminology (BETT) (Table 1).5

Ocular trauma severity is calculated by ocular trauma score (OTS) (Table 2).6

The National Academy of Sciences has called trauma the ‘neglected epidemic of modern society,’7 Ocular trauma in children can result in catastrophic visual and psychological outcomes both for the child and his/her family. According to the World Health Organization (WHO), childhood blindness is one of the major causes of avoidable blindness and so target of the Vision 2020 Program. According to a rough estimate, 5-10% of cases of childhood blindness are due to trauma.8

Despite the strong anatomical barrier and vigilant physiological protection provided by nature to the eye, the incidence of ocular injuries remains high. The fate of the traumatized eye depends upon the treatment adopted. Timely reporting of cases and early surgical management reduces the visual loss. Promptness in decision of action in emergency is the best test of the powers and resources of any man, especially medical men. Annually, more than two million cases of eye trauma are reported, out of which more than 40,000 cases end up with severe visual impairment accounting for socioeconomic burden. Most of the cases are less than 40 years of age and 90% blindness due to trauma is preventable.

MAnAgeMent of PenetrAting ocUlAr injUry

Management varies widely according to severity, extent and location of the injury. Some general principles which apply are:

Primary closure of the penetrating woundRemoval of any foreign body materialPenetrating of further or secondary injury to eye (infection)Anatomic and visual rehabilitation of the eyeProtection of the fellow uninvolved eye (protective eye wear)General rehabilitation of the patient.

cAse rePort

A 12-year-old male child presented to the OPD in our Institute with a history of injury in his left eye with an iron nail while playing. After the injury, the patient had diminution of vision, mild pain, irritation and

*Assistant Professor**Senior Resident†Ex-Senior ResidentRegional Institute of Ophthalmology, Pt. BD Sharma Postgraduate Institute of Medical Sciences (PGIMS), Rohtak, HaryanaAddressforcorrespondenceDr Jitender Kumar PhogatAssistant Professor, Regional Institute of OphthalmologyPostgraduate Institute of Medical Sciences (PGIMS), Rohtak -124 001, HaryanaE-mail: [email protected]

CAserePort

CAserePort


watering from the affected eye. He did not seek any medical help for two days, but when the symptoms did not subside, the patient presented to us, where on examination patient had a visual acuity of 6/6 in right eye (R/E) and 6/36 in left eye (L/E). On slit-lamp examination, his R/E was within normal limits (WNL) and the left eye had mild superficial and deep congestion. A scleral tear with iris prolapse of 4 mm was present from 8 O’clock to 10 O’clock. The adjacent 2-3 mm of cornea had stromal edema. Anterior chamber had cells and flare of Grade 2 and fundal glow was present. After prescribing injection tetanus toxoid (TT) 0.5 mg IM, he was put on one hourly preservative-free moxifloxacin and injection ciprofloxacin 75 ml b.i.d. After taking consent and proper anesthetic check-up, the patient was operated upon under general anesthesia. During the

operation, the iris was abscised and the scleral tear was repaired with 9-0 monofilament polyamide. Intravitreal injection, vancomycin and ceftazidime were given in recommended therapeutic dosage. Postoperatively, the patient was put on injection ciprofloxacin 75 ml b.i.d., tablet prednisolone 30 mg after breakfast and capsule lansoprazole 30 mg BBF and pad and bandage was applied for 24 hours. On the first postoperative day, his vision was 6/18 and patient was put on fortified vancomycin, fortified ceftazidime, preservative-free moxifloxacin eye drops 0.3% one hourly, bromfenac eye drops 0.09% b.i.d., atropine eye drops 1% t.i.d. and natamycin 5% eye drops.

Postoperatively at two weeks, his vision in L/E was 6/9 and in R/E, the vision was 6/6 with refraction (Figs. 1 and 2).

Table 1. The Birmingham Eye Trauma Terminology5

Glossary of terms Definition and explanation

EyewallClosed globe injury Open globe injuryContusion

Lamellar lacerationRuptureLacerationPenetrating injury

Perforating injury

Sclera and corneaNo full-thickness wound of eyewallFull-thickness wound of the eyewallThere is no (full-thickness) wound (Due to direct energy delivery by the object e.g., choroidal rupture or to the changes in the shape of the globe e.g., angle recession)Partial thickness wound of the eyewallFull-thickness wound of the eyewall, caused by a blunt object (Inside - out mechanism).Full-thickness wound of the eyewall, caused by a sharp object (By an outside - in mechanism).Entrance wound (If more than one wound is present, each must have been caused by a different agent. Retained foreign object/s are technically a penetrating injury, but grouped separately because of different clinical implications).Entrance and exit wounds (Both wounds caused by the same agent).

Table 2. The Ocular Trauma Score (Version 11.1) Computational Method for Deriving the OTS6

Initial visual factor Raw point

Initial visual acuity category

Globe ruptureEndophthalmitisPerforating injuryRetinal detachmentAfferent pupillary defect (Marcus Gunn pupil)Raw score sum = sum of raw points

NLPLP/HM

1/200-19/20020/200-20/50

≥20/40

60708090

100–23–17–14–11–10

HM: Hand movements; LP: Light perception; NLP: No light perception.

CAserePort


discUssion

Prognosis for vision depends upon severity of initial penetrating injury. The most important factors on which final visual outcome depends include initial visual acuity, presence of an afferent pupillary defect and presence of infection. The presence of massive choroidal detachment and posterior exit wounds, retinal detachment, or subretinal hemorrhage, large corneoscleral laceration are associated with worse visual outcome.

X-ray is an easy tool to look for any metallic foreign body. Diagnostic ultrasound may provide useful information. Computed tomography (CT) and magnetic resonance imaging (MRI) are also very helpful for assessment of injury. Proper surgical repair, prevention of infection and sympathetic ophthalmitis in normal eye are key for optimal outcome.

conclUsion

Penetrating ocular injuries present a challenge to salvage useful vision in injured eye. Prevention, early presentation and proper management help to save vision and early rehabilitation of the patient.

references

Punnonen E. Epidemiological and social aspects of perforating eye injuries. Acta Ophthalmol (Copenh) 1989;67(5):492-8.Blomdahl S, Norell S. Perforating eye injury in the Stockholm population. An epidemiological study. Acta Ophthalmol (Copenh) 1984;62(3):378-90.Moreira CA Jr, Debert-Ribeiro M, Belfort R Jr. Epidemiological study of eye injuries in Brazilian children. Arch Ophthalmol 1988;106(6):781-4.National Society to Prevent Blindness: Fact sheet. National Society to Prevent Blindness: New York, 1980.Kuhn F, Morris R, Witherspoon CD, Heimann K, Jeffers JB, Treister G. A standardized classification of ocular trauma. Ophthalmology 1996;103(2):240-3.Kuhn F, Maisiak R, Mann L, Mester V, Morris R, Witherspoon CD. The Ocular Trauma Score (OTS). Ophthalmol Clin North Am 2002;15(2):163-5, vi.Committee on Trauma and Committee on Shock. Accidental death and disability: the neglected disease of modern society. National Academy Press: Washington 1966:p.5. Available at: http://http://www.nap.edu/catalog.php?record_id=9978. Accessed April 17, 2006.Shukla B, Natarajan S. Management of ocular trauma. 2005:288.

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Figure 1. Preoperative case of penetrating injury to eye. Figure 2. Postoperative picture of the same patient.


PHS Updates Smoking Cessation Guideline

The Public Health Service of the U.S. Department of Health and Human Services has released an update of the 1996 smoking cessation guideline

that was developed by the Agency for Health Care Policy and Research (now called the Agency for Healthcare Research and Quality [AHRQ]). “Treating Tobacco Use and Dependence” was developed in response to the new data and the new treatments for tobacco dependence that have emerged since the mid-1990s. In addition to AHRQ, other sponsors of the guideline are the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute, the National Institute on Drug Abuse, the Robert Wood Johnson Foundation and the University of Wisconsin Medical School Center for Tobacco Research and Intervention.

The guideline is available on the Surgeon General’s Web site athttp://www.surgeongeneral.gov/tobacco/default.htm. It also may be obtained by calling AHRQ at 800-358-9295, the CDC at 800-CDC-1311 (800-232-1311) or the NCI at 800-4-CANCER (800-422-6237). The updated guideline contains eight chapters, which include information on assessment of tobacco use; effective brief interventions to encourage smoking cessation; treatment approaches; health care coverage; statistical evidence in support of the recommendations and special populations, such as women, pregnant smokers, hospitalized patients, racial and ethnic minorities, smokers with psychiatric conditions, children and adolescents, and the elderly. There is also a chapter on special topics, such as weight gain after smoking cessation, chewing tobacco, training of physicians and the economics of tobacco treatment.

coMPArison with the 1996 sMoking cessAtion gUideline

The guideline explains that the updated version includes data that attest to the progress made in tobacco research and treatment since the development of the 1996 clinical practice guideline. Tobacco dependence is now generally

recognized as a chronic disease that requires repeated interventions. The guideline includes information on the use of any of the seven different agents now available to aid in smoking cessation. In addition, data now suggest that the combination of nicotine replacement therapy and drug therapy, with the use of medications such as bupropion or nortriptyline, may be more effective than nicotine replacement therapy alone. The guideline also notes that use of two different forms of nicotine replacement, such as the patch and gum, maybe helpful in patients who are unable to quit smoking when using a single type of nicotine replacement.

The updated guideline points to the strong association between the intensity of counseling and success at smoking abstinence. Research has identified telephone counseling as an effective strategy for providing social support during a patient’s smoking cessation efforts. The guideline recognizes that the combination of pharmacotherapy and counseling may be optimal.

The updated guideline makes a case for insurance coverage for the treatment of smoking cessation. The guideline points out that treatments of smoking cessation are cost-effective relative to other routinely reimbursed medical interventions, such as treatment of hyperlipidemia and mammography screening.

coMbinAtion nicotine rePlAceMent therAPy

The U.S. Food and Drug Administration has not approved the use of two different forms of nicotine replacement. Because there is relatively little safety data on combination nicotine replacement therapies and they can increase the risk of nicotine overdoses, the guideline recommends such treatment only in patients who are unable to quit smoking with a single type of nicotine replacement. According to the guideline, combining the nicotine patch with a self-administered form of nicotine replacement, such as nicotine gum or nicotine nasal spray, is more effective than treatment with a single form of nicotine replacement.

This recommendation is based on a meta-analysis of three studies. All three studies used the nicotine patch in a 15 mg dosage. In two of the studies, nicotine gum was used to supplement the patch, and in the

PrACtICeguIdelInes

Source: Adapted from Am Fam Physician. 2001;63(8):1635-1636.


other study, nicotine nasal spray was used. With this approach, the nicotine patch provides a relatively steady level of nicotine while self-administered nicotine gum or nasal spray allows the patient to modify the nicotine dose as needed for symptoms of nicotine withdrawal. Combination nicotine replacement therapy was found to produce higher long-term abstinence rates than monotherapy. The combination of the nicotine patch and nicotine gum was found to suppress symptoms of nicotine withdrawal.

key recoMMendAtions

The following is an excerpt from the key recommendations outlined in the updated guideline:

Tobacco dependence is a chronic condition that often requires repeated intervention. However, there are effective treatments that can produce long-term or even permanent abstinence.Because effective treatments of tobacco dependence are available, every patient who uses tobacco should be offered at least one of these treatments, as follows:

Patients who are willing to try to stop using tobacco should be provided treatments that have been identified as effective in this guideline.Patients who are unwilling to quit using tobacco should be provided a brief intervention designed to increase their motivation to quit.

It is essential that physicians and health care delivery systems (including administrators, insurers and purchasers) institutionalize the consistent identification, documentation and treatment of every tobacco user seen in a health care setting.Brief tobacco dependence treatment is effective, and every patient who uses tobacco should be offered at least brief treatment.There is a strong dose-response association between the intensity of tobacco dependence counseling and its effectiveness. Treatments that involve person-to-person contact (by means of individual, group

or proactive telephone counseling) are consistently effective, and their effectiveness increases with the intensity of treatment (e.g., minutes of contact).Three types of counseling and behavioral therapies were shown to be especially effective and should be used with all patients who are attempting cessation of tobacco use:

Provision of practical counseling (problem solving and skills training).Provision of social support as part of treatment.Help in securing social support outside of treatment.

Numerous effective pharmacotherapies for smoking cessation now exist. Except in the presence of contraindications, these should be used with all patients attempting to quit smoking:

Five first-line pharmacotherapies that reliably increase long-term smoking abstinence rates were identified: bupropion sustained-release, nicotine gum, nicotine inhaler, nicotine nasal spray and nicotine patch.Two second-line pharmacotherapies, clonidine and nortriptyline, were identified as efficacious and may be considered by physicians if first-line pharmacotherapies are not effective.Over-the-counter nicotine patches are effective relative to placebo, and their use should be encouraged.

Treatments of tobacco dependence are clinically effective and cost-effective relative to other medical and disease prevention interventions. As such, insurers and purchasers should ensure the following:

That all insurance plans include, as a reimbursed benefit, the counseling and pharmacotherapies identified as effective in this guideline.That physicians are reimbursed for providing treatment of tobacco dependence just as they are reimbursed for the treatment of other chronic conditions.

PrACtICeguIdelInes


PhotoQuIz

Linear Lesions in a Neonate

A male infant was born via uncomplicated vaginal delivery at 42 weeks’ gestation after a normal pregnancy. Linear, skin-colored plaques were

noted at birth (Figures 1 and 2). The plaques followed the embryologic clonal expansion lines (Blaschko lines) and were most prominent on the left hand, arm, axilla, and trunk.

The child was large for gestational age, but physical examination findings were otherwise normal. Two days after birth, a vesicular component developed more diffusely. Results of a Tzanck smear and complete blood count with differential were normal. The vesicles resolved by one week of age, with the lesions returning to their original state.

QUestion

Based on the patient’s history and physical examination, which one of the following is the most likely diagnosis?

Source: Adapted from Am Fam Physician. 2011;83(6):755-756.

Figure 1. Figure 2.

A. Epidermal nevi.

B. Incontinentia pigmenti.

C. Infantile acropustulosis.

D. Neonatal herpes simplex virus infection.

SEE THE FOLLOWING PAGE FOR DISCUSSION.


discUssion

The correct answer is A: epidermal nevi.

Epidermal nevi are hamartomatous proliferations of the epidermis and papillary dermis, thought to originate from pluripotent cells in the basal layer of the embryonic epidermis. The condition includes verrucous, sebaceous, pilosebaceous, and eccrine subtypes. Epidermal nevi occur in one out of 1,000 live births, and 80 percent of cases appear in the first year of life.1,2 The nevi are generally unilateral, following Blaschko lines in linear configurations on the limbs. The condition can be associated with syndromes that manifest with developmental abnormalities of the nervous, cardiovascular, urogenital, or skeletal systems. Children born with more extensive lesions should be monitored closely early in life. Treatment consists of full-thickness surgical excision or ablation. Topical treatments, such as steroids, retinoids, tars, and fluorouracil, have only limited benefit.

Incontinentia pigmenti is an X-linked dominant disease and is often fatal in male fetuses. It almost always occurs in female infants and is associated with cutaneous lesions that appear in four phases: vesicular, verrucous, hyperpigmented, and atrophic.3 Lesions appear in the first three weeks of life and follow Blaschko lines. During the vesicular phase, the rash is predominantly located on the lower extremities, and histology demonstrates eosinophilic spongiosis. The condition is often associated with extracutaneous findings, including dental, central nervous system, and ocular abnormalities. Infants with incontinentia pigmenti require baseline ophthalmologic examination, and periodic dental and neurodevelopmental evaluation.

Infantile acropustulosis typically occurs between three and six months of age, and occasionally at birth. It is associated with recurrent crops of pruritic vesicopustular lesions, primarily on the palms and soles. The condition can be misdiagnosed as scabies infection. The lesions begin as pinpoint papules, progressing into vesicles over the course of a day, and then disappear in a variable amount of time. Recurrences usually stop around three or four years of age.

Neonatal herpes simplex virus (HSV) is usually transmitted during vaginal birth, presenting as a vesicular rash on the face or scalp in the first seven to 10 days of life.4 Lesions that appear in the first 24 hours of life suggest an in utero infection, which more often causes erosions than vesicles. Tzanck smear has 79 percent sensitivity and 100 percent specificity for the diagnosis of HSV infection.5 Cultures of skin lesions,

nasopharynx, eyes, and cerebrospinal fluid should be obtained, as well as polymerase chain reaction testing if available. Disseminated neonatal HSV infection may not lead to skin lesions and has a 57 percent mortality rate.6

references

Solomon LM, Esterly NB. Epidermal and other congenital organoid nevi. Curr Probl Pediatr. 1975;6(1):1-56.Cockerell CL, Larsen F. Benign epidermal tumors and proliferations. In: Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology. 2nd ed. St. Louis, Mo.: Mosby; 2008: 1671-1672.Gilliam AE, Pauporté M, Frieden I. Vesiculobullous and erosive diseases in the newborn. In: Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology. 2nd ed. St. Louis, Mo.: Mosby; 2008:484-485.Drolet BA, Esterly NB. The skin. In: Fanaroff AA, ed. Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant. 7th ed. St. Louis, Mo.: Mosby; 2002:1537.Ozcan A, Senol M, Saglam H, et al. Comparison of the Tzanck test and polymerase chain reaction in the diagnosis of cutaneous herpes simplex and varicella zoster virus infections. Int J Dermatol. 2007;46(11):1177-1179.Whitley R, Arvin A, Prober C, et al. Predictors of morbidity and mortality in neonates with herpes simplex virus infections. N Engl J Med. 1991;324(7):450-454.

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Selected Differential Diagnosis of Rash in a NeonateCondition CharacteristicsEpidermal nevi Lesions are generally unilateral, following

Blaschko lines in a linear configuration; may be related to developmental abnormalities

Incontinentia pigmenti

X-linked dominant disease almost always occurring in female infants, usually in the first three weeks of life; lesions follow Blaschko lines; associated with dental, central nervous system, and ocular abnormalities

Infantile acropustulosis

Recurrent crops of pruritic vesicopustular lesions that usually resolve by three or four years of age; lesions primarily appear on the palms and soles and look similar to scabies

Lichen striatus Rare, idiopathic linear eruption on the extremities that are self-limited and sometimes pruritic; lesions appear between four months and 15 years of age, usually in girls; associated with atopic dermatitis

Linear psoriasis

Erythematous, scaly papules and plaques; linear distribution; typically occur on the extremities

Neonatal herpes simplex virus infection

Vesicular rash often appears on the face or scalp in first seven to 10 days of life; usually transmitted during vaginal birth; risk of disseminated infection

PhotoQuIz


medIlAw

Illegal PathlabsmCguPtA

Q. What action can be taken by the medical profession against illegal pathlabs?

Ans.

1. Illegal pathlabs include the following:

a. Pathlabs run by non-medical people, such as DMLT technicians, biochemists, microbiologists etc.

b. Pathlabs run by non-medical people who get the reports signed by a pathologist for payment of ‘signing fee’ but there is no actual supervision of testing by the pathologist.

c. Pathlabs violating any central or state law as applicable.

I will concern myself only with the first two.

2. The Indian Medical Association (IMA) or an association of pathologists or both together should engage an advocate to study the problem and initiate practically feasible legal actions.

3. Some of the possible legal actions are as follows:

a. Complaint to medical council for quackery

b. Complaints to the concerned council (Bharatiya Chikitsa Council, Homeopathy Council; Paramedical Council, etc.)

c. Complaint to consumer court for deficiency and negligence in service, invoking quackery

d. Complaint to police for quackery.

e. Complaint under Clinical Establishment Act, if applicable in the state.

f. Complaint to the medical council against another physician licensed by the council under Regulation 1.7 of the Indian Medical Council (Professional conduct, Etiquette and Ethics) Regulations, 2002, for unethical conduct of the following types:

i) Associating with quacks by referring cases to them and by relying on reports given by them. Those who practice pathology without having a medical qualification are quacks.

ii) Mechanical signing of illegal pathlab reports by pathologists

iii) Running a pathlab without having a qualification in pathology.

g. Direct complaint to the DM or SDM under Section 133 (1)(b), CrPC. The SDM Jalgaon, Maharashtra, sealed illegal Pathlabs under Section 133 CrPC on a complaint dated 11-1-2010. A final order against the illegal labs was passed by the SDM on 13-5-2011. Similar action can be taken in other states.

h. A writ petition or a Public Interest Litigation (PIL) in the High Court. If pathologists in Madhya Pradesh, Maharashtra and Gujarat can go to High Court, there is no reason other than complacence why those in other states cannot do so.

Advocate and Medicolegal Consultant, New Delhi


Lighter Side of Medicine

‘god bless yoU’ sPeech

They walked in tandem, each of the ninety-three students filing into the already crowded auditorium. With rich maroon gowns flowing and the traditional caps, they looked almost as grown up as they felt.

Dads swallowed hard behind broad smiles, and moms freely brushed away tears.

This class would not pray during the commencements; not by choice, but because

of a recent court ruling prohibiting it. The principal and several students were careful to stay within the guidelines allowed by the ruling.

They gave inspirational and challenging speeches, but no one mentioned divine guidance and no one asked for blessings on the graduates or their families.

The speeches were nice, but they were routine; until the final speech received a standing ovation.

A solitary student walked proudly to the microphone. He stood still and silent for just a moment, and then he delivered his speech - a resounding sneeze! The rest of the students rose immediately to their feet, and in unison they said, “God bless you.”

The audience exploded into applause. The graduating class found a unique way to invoke God’s blessing on their future - with or without the court’s approval.

(Source: http://www.inspire21.com/stories/educationstories)

AnIn

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Dr. Good & Dr. Bad

Dr KK Aggarwal

SITuATION:

lESSON:

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CP

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A 36-year-old executive used to take 5 pegs of alcohol once a week.

The French habit of drinking wine almost daily is less taxing to the heart than the Irish custom of downing an equivalent amount of beer on one or two nights a week, according to a study published in the British Medical Journal.

lAug

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le

VirUses

Coming to a hard drive near you, the worst computer viruses yet:

AT&T virus: Every three minutes it tells you what great service you’re getting.Government Economist virus: Nothing works, but all your diagnostic software says everything is fine.Politically correct virus: Never calls itself a “virus.” Instead, it’s an “electronic microorganism.”Government Spokesman virus: Nothing works but all your diagnostic software says everything is fine.Right to life virus: Won’t allow you to delete a file, regardless of how old it is. If you attempt to erase a file, it requires you to first see a counselor about possible alternatives.

—Dr GM Singh

Either stop it or just take one peg a day

Continue it

Quot

es

“Destiny is no matter of chance. It is a matter of choice: It is not a thing to be waited for, it is a thing to be achieved.”

—William Jennings Bryan

ILLUSION


Manuscripts should be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767).Indian Journal of Clinical Practice strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so.The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript.Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper.

Covering letter

– The covering letter should explain if there is any deviation from the standard IMRAD format (Introduction, Methods, Results and Discussion) and should outline the importance of the paper.

– Principal/Senior author must sign the covering letter indicating full responsibility for the paper submitted, preferably with signatures of all the authors.

– Articles must be accompanied by a declaration by all authors stating that the article has not been published in any other Journal/Book. Authors should mentioned complete designation and departments, etc. on the manuscript.

Manuscript– Three complete sets of the manuscript should be

submitted and preferably with a CD; typed double spaced throughout (including references, tables and legends to figures).

– The manuscript should be arranged as follow: Covering letter, Checklist, Title page, Abstract, Keywords (for indexing, if required), Introduction, Methods, Results, Discussion, References, Tables, Legends to Figures and Figures.

– All pages should be numbered consecutively beginning with the title page.

Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be returned to authors.

Title pageShould contain the title, short title, names of all the authors (without degrees or diplomas), names and full location of the

departments and institutions where the work was performed, name of the corresponding authors, acknowledgment of financial support and abbreviations used.– The title should be of no more than 80 characters and

should represent the major theme of the manuscript. A subtitle can be added if necessary.

– A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included.

– The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page.

– A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text.

Summary– The summary of not more than 200 words. It must

convey the essential features of the paper.– It should not contain abbreviations, footnotes or

references.

Introduction– The introduction should state why the study was carried

out and what were its specific aims/objectives.

Methods– These should be described in sufficient detail to permit

evaluation and duplication of the work by others.– Ethical guidelines followed by the investigations should

be described.

StatisticsThe following information should be given:– The statistical universe i.e., the population from which

the sample for the study is selected.– Method of selecting the sample (cases, subjects, etc.

from the statistical universe).– Method of allocating the subjects into different

groups.– Statistical methods used for presentation and analysis of

data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques.

– Confidence intervals for the measurements should be provided wherever appropriate.

Results– These should be concise and include only the tables

and figures necessary to enhance the understanding of the text.

Information for Authors


Discussion

– This should consist of a review of the literature and relate the major findings of the article to other publications on the subject. The particular relevance of the results to healthcare in India should be stressed, e.g., practicality and cost.

ReferencesThese should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses). At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution.Examples of common forms of references are:

ArticlesPaintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes. Q. J. Expt. Physiol. 1955;40:89-111.

BooksStansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985.

Articles in BooksStrong MS. Recurrent respiratory papillomatosis. In: Scott Brown’s Otolaryngology. Paediatric Otolaryngology Evans JNG (Ed.), Butterworths, London 1987;6:466-470.

Tables– These should be typed double spaced on separate

sheets with the table number (in Roman Arabic numerals) and title above the table and explanatory notes below the table.

legends– These should be typed double spaces on a separate

sheet and figure numbers (in Arabic numerals) corresponding with the order in which the figures are presented in the text.

– The legend must include enough information to permit interpretation of the figure without reference to the text.

Figures– Two complete sets of glossy prints of high quality

should be submitted. The labelling must be clear and neat.

– All photomicrographs should indicate the magnification of the print.

– Special features should be indicated by arrows or letters which contrast with the background.

– The back of each illustration should bear the first author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen.

– Color illustrations will be accepted if they make a contribution to the understanding of the article.

– Do not use clips/staples on photographs and artwork.

– Illustrations must be drawn neatly by an artist and photographs must be sent on glossy paper. No captions should be written directly on the photographs or illustration. Legends to all photographs and illustrations should be typed on a separate sheet of paper. All illustrations and figures must be referred to in the text and abbreviated as “Fig.”.

Please complete the following checklist and attach to the manuscript:1. Classification (e.g. original article, review, selected

summary, etc.)_______________________________2. Total number of pages ________________________3. Number of tables ____________________________4. Number of figures ___________________________5. Special requests _____________________________6. Suggestions for reviewers (name and postal address) Indian 1. ___________Foreign 1. _______________ 2. ___________ 2. _______________ 3. ___________ 3. _______________ 4. ___________ 4. _______________7. All authors’ signatures________________________8. Corresponding author’s name, current postal and

e-mail address and telephone and fax numbers __________________________________________

For Editorial CorrespondenceDr KK AggarwalGroup Editor-in-Chief

Indian Journal of Clinical PracticeE-219, Greater Kailash, Part-1

New Delhi - 110 048. Tel: 40587513E-mail: [email protected] Website: www.ijcpgroup.com

Online Submission Also e- Issue @ www.ijcpgroup.com

Documents

IJCP Oct ober 2012