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All Efforts of Worth and Excellence Are Difficult

“Enter by the narrow gate ….Because narrow is the gate and difficult is the way which leads to life …” (Matthew 7:13-14).

If we are going to live as disciples of Jesus, we have to remember that all efforts of worth and excellence are difficult. The Christian life is gloriously difficult, but its difficulty does not make us faint and cave in – it stirs us up to overcome. Do we appreciate the miraculous salvation of Jesus Christ enough to be our utmost for His highest – our best for His glory?

God saves people by His sovereign grace through the atonement of Jesus, and “it is God who works in you both to will and to do for His good pleasure” (Philippians 2:13). But we have to “work out” that salvation in our everyday, practical living (Philippians 2:12). If we will only start on the basis of His redemption to do what He commands, then we will find that we can do it. If we fail, it is because we have not yet put into practice what God has placed within us. But a crisis will reveal whether or not we have been putting it into practice. If we will obey the Spirit of God and practice in our physical life what God has placed within us by His Spirit, then when a crisis does come we will find that our own nature, as well as the grace of God, will stand by us.

Thank God that He does give us difficult things to do! His salvation is a joyous thing, but it is also something that requires bravery, courage, and holiness. It tests us for all we are worth. Jesus is “bringing many sons to glory” (Hebrews 2:10), and God will not shield us from the requirements of sonship. God’s grace produces men and women with a strong family likeness to Jesus Christ, not pampered, spoiled weaklings. It takes a tremendous amount of discipline to live the worthy and excellent life of a disciple of Jesus in the realities of life. And it is always necessary for us to make an effort to live a life of worth and excellence.

Oswald Chambers

My utmost for His highest


Back cover photo
Spotted Owlets – (Athene Brama) grooming each other

Location: Hathikhira Tea Estate, Karimganj District, Assam (f 11, 1/500, 500mm, ISO-500)

Photo by Dr. Vijay Anand Ismavel. See more images at

Spotted owlets are medium sized birds, commonly seen in south and South east Asia. They usually are seen in small groups roosting in the hollows of trees or in cavities in rocks or buildings. It nests in a hole in a tree or building, laying 3–5 eggs. Their main prey includes beetles, moths and other insects and they often hunt at night. Earthworms, lizards, mice and small birds also form part of their diet. They usually hunt from a perch, pouncing on prey, but occasionally take insects in flight.

Dr. Vijay Anand, a pediatric surgeon, works in Makunda Christian Leprosy & General Hospital in Makunda, Assam, a 132 bedded hospital providing high quality care to residents in Assam and surrounding states. The hospital is situated in a lush forest abounding in wildlife and this photograph was taken in a tea estate close to the hospital. Learn more about the hospital at

CME in images

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Test your knowledge by answering the questions provided along with the two sets of images and case scenarios. The answers and a short description are given on the next page.

Case 1:

Case scenario: A gentle man in his late 50s presented to the OPD. He had been suffering from prolonged general ill health and chronic cough. Currently he is worried by development of gradually progressive swelling over face and neck.
1) What is the clinical diagnosis?
2) What would be the 1st line investigations?
3) What would be the recommended line of treatment?

Case 2:


Case Scenario

  • A 30 year old lady with sudden onset, severe intermittent colicky pain abdomen associated with multiple episodes of non projectile, non bilious vomiting for one week. Clinical examination revealed an ill defined palpable mass in the right iliac fossa. Blood investigations were within normal limits. Ultrasound and CT abdomen of the lady are shown above.
  • What is your diagnosis after having seen the images?
  • What are the significant findings in the images that point to a diagnosis?
  • What are the investigations you would order in this patient (adult) and in a child who presents with similar clinical features?


Case 1

Dr. Benjamin Barsouma Mathew & Dr. Tony Bishwas, Harriet Benson Memorial Hospital, Lalitpur, UP

This elderly gentleman has presented with generalised fatigue, chronic cough and recentonset progressive swelling of face and neck. There is oedema of the face and arms associated with plethora and swollen collateral veins on the front and back of the chest wall and arms. An obstruction to the Venous Drainage from upper part of body leading to extravasation of fluid and oedema and opening up of collaterals leading to engorged veins in chest wall explains the clinical picture. The clinical Diagnosis will be that of a Superior Vena Cava syndrome.

Superior vena cava (SVC) syndrome is the constellation of symptoms and signs that results from effective obstruction of blood flow at the level of the SVC itself, the great veins as they empty into the SVC, or the superior cavo-atrial junction .SVC syndrome was first described by William Hunter in 1757 in a patient with a large syphilitic aortic aneurysm compressing the SVC. Because the venous drainage from the upper extremities, upper thorax and head is obstructed, SVC syndrome presents with symptoms related to engorgement of these areas.1The various manifestations of SVC syndrome is summarised in Table 1, the most common ones being facial and neck swelling, dyspnoea and cough2.

The causes of SVC syndrome are summarised in Table 23.The most common cause today is a Bronchogenic Carcinoma compressing the SVC1,2,3. Such a mass is usually visible on a chest X-Ray making it the first investigation of choice. The X Ray of this patient(Fig 1) showed a right upper zone , well defined round homogenous opacity, most probably bronchogenic in origin. A Computed Tomography may be indicated to define the level and extent of venous blockage, map the collaterals and identify and stage the underlying cause.Conventional superior vena cavography is the gold standard for identification of SVC obstruction and the extent of associated thrombus formation2 .Investigations for diagnosing and staging the underlying cause are done in parallel.

The goals of management for SVC syndrome associated with malignancy are to alleviate symptoms and treat the underlying disease. Contrary to the earlier belief, not all cases of SVC syndrome requires emergency management3.The general principles of management of SVC syndrome are3,4

  • Head elevation to decrease venous stasis
  • Preventing injections to arm to avoid thrombosis in presence of pre-existing stasis
  • Removal of indwelling catheters, which might have precipitated a thrombus
  • Anticoagulation if thrombus is the cause
  • Glucocorticoids are found to effective in steroid responsive tumours(eg:Lymphomas) and RT induced SVC syndrome
  • Diuretics to alleviate symptoms are often used, although with questionable benefit
  • Chemotherapy, Radiotherapy or Surgery for the primary disease according to the tissue diagnosis and stage (in case of external compression)
  • Endovascular stenting, often as an emergency procedure in acute cases or as a palliative procedure.
  • A surgical SVC bypass, in specific circumstances, where a stenting is not possible


1. Cohen, Ronny et al. “Superior Vena Cava Syndrome: A Medical Emergency?” The International Journal of Angiology: Official Publication of the International College of Angiology, Inc 17.1 (2008): 43–46.

2. The Superior Vena Cava Syndrome: Clinical Characteristics and Evolving Etiology,Rice et al; Medicine Jan 2006

3. Superior Vena Cava Syndrome: A Contemporary Review of a Historic Disease;Cheng, Susan MDCardiology in Review;Volume 17(1), January/February 2009, pp 16-23

4. Yu JB, Wilson LD, Detterbeck FC. Superior vena cava syndrome-Aproposed classification system and algorithm for management. J ThoracOncol 2008; 3:811.


Drs. Madhavi. K / Geethu Punnen / Shyamkumar N. K.- Dept. of Radiodiagnosis, CMC Vellore

DIAGNOSIS: Jejuno-jejunal intussusception with lipoma as lead point


  • Intussusception is the most common cause of intestinal obstruction in infants and toddlers. It is defined as telescoping of a segment of bowel (intussusceptum) into a distal segment of the bowel (intussuscipiens). There is usually a ‘lead point’- a malignant or benign mass that pulls one bowel segment into another.
  • The most common type is ileocolic, followed by ileoileocolic, ileoileac and colocolic. Jejuno-jejunal intussusception (as in this case) is uncommon.
  • In children, there is no defined lead point, commonly associated with lymphoid hypertrophy following a viral illness. Intussusception is rare in adults; 90% of cases will have a demonstrable cause (neoplasms account for 60% of cases, followed by inflammation, trauma, adhesions).


  • Children present with a triad of colicky abdominal pain, vomiting and red currant jelly stools.
  • Adults usually have an indolent course, with recurrent abdominal pain, vomiting and rarely palpable mass .
  • Ultrasound is the investigation of choice in children. In adults, ultrasound is the base line investigation, followed by cross sectional examination (CT) to assess the cause for the intussusception .


Patients will have to be kept nil per oral (NPO), IV fluids have to be initiated. Children will require Barium or hydrostatic reduction, air enema or surgery. Adults will require surgical reduction (in malignancy) or resection without reduction (benign lesion). This lady underwent laparotomy, reduction of intussusception and excision of sub mucosal lipoma.


  • Longitudinal ultrasound image shows thickened, edematous hypoechoic outer bowel – intussuscipiens with echogenic central collapsed, telescoping inner segment – intussusceptum and associated mesenteric fat
  • Transverse ultrasound image shows an outer edematous, hypoechoic bowel loop with central collapsed telescoping segment of bowel with associated mesentery giving a target or doughnut sign
  • There is colour uptake within suggesting preserved vascularity



Fig. 1: Longitudinal ultrasound image. Fig.2: Transverse ultrasound image

1= outline of hypoechoic outer bowel, 2= collapsed inner segment, 3= mesenteric fat (Compare these images with the earlier images )


Figure 3: Longitudinal ( Fig.3: upper image) and serial cross sectional (Fig.3: lower image) diagrams illustrate intussusception with a lead point.

The thick arrows indicate lead mass. The intussusceptum appears thick with loss of gut signature due to edema. (Image source: Radiographics 2006;Vol 26: 733-744)



Fig.4: CT coronal section, Fig.5: CT transverse section

Arrows 1- outline of outer bowel loop, 2- collapsed inner bowel, 3 – Lipoma as the lead point (Compare with earlier images)

The CT coronal image (Fig.4) shows telescoping of the proximal jejunal loops and along with mesenteric vessels into distal jejunal loop.

CT transverse section (Fig.5) shows well defined fat attenuation lesion – lipoma (3) as lead point

(Compare these images with the earlier images)

Drug dialogues

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Risk of intracranial bleeding with antidepressants and NSAIDs

Concomitant use of antidepressants and nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a significantly increased risk of intracranial haemorrhage (ICH) in the first 30 days after the drugs are taken together, a large cohort study published in The BMJ (2015;351:h3517) has found. Using a national Korean health insurance database to create a propensity score matched cohort, the researchers calculated a hazard ratio (HR) for ICH of 1.6 (95% confidence interval [CI] 1.32—1.85) for combined use of antidepressants and NSAIDs versus use of antidepressants alone. Subgroup analysis indicated that the risk was higher in men than in women, with HRs of 2 (95% CI 1.93—3.42) and 1.2 (95% CI 0.89—1.57), respectively, but did not vary depending on the other characteristics examined, which included age, ICH subtype, comorbidity and other medication. Also, the risk of ICH did not apparently differ among different classes of antidepressants, namely, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs) and serotoninnor-epinephrine reuptake inhibitors.
       The researchers say they undertook their study because, while antidepressants and NSAIDs are each known to increase the risk of gastrointestinal bleeding, little was known about the combined effect of these drugs on the risk of ICH. The addition of NSAIDs to antidepressant treatment increased the risk of intracranial haemorrhage within 30 days of starting the combination especially in men. Both antidepressants and NSAIDs are widely prescribed; furthermore, NSAIDs are often used without prescription. Although NSAIDs bought over the counter are often taken for a short period only, the study reported elevated bleeding risk within 30 days of a new prescription. Patients with risk factors for increased bleeding tendency who are taking an antidepressant should use a NSAID with caution.

New treatment for chronic hepatitis C

The US Food and Drug Administration has approved daclatasvir for use with sofosbuvir to treat hepatitis C virus (HCV) genotype 3 infections. Daclatasvir is the first drug that has demonstrated safety and efficacy to treat genotype 3 HCV infections without the need for co-administration of interferon or ribavirin. The safety and efficacy of daclatasvir in combination with sofosbuvir were evaluated in a clinical trial of 152 treatment-naïve and treatment experienced participants with chronic HCV genotype 3 infection. Participants received daclatasvir 60 mg with sofosbuvir 400 mg once daily for 12 weeks and were monitored for 24 weeks post treatment. The studies were designed to measure whether a participants hepatitis C virus was no longer detected in the blood 12 weeks after finishing treatment (sustained virologic response), suggesting a participant’s infection had been cured. Results showed that 98% of the treatment-naïve participants with no cirrhosis of the liver and 58% of the treatment-naïve participants with cirrhosis achieved sustained virologic response. Of the participants who were treatment experienced, 92% with no cirrhosis of the liver and 69% with cirrhosis achieved sustained virologic response. The most common side-effects of daclatasvir with sofosbuvir were fatigue and headache. Serious symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is co-administered with sofosbuvir in combination with another HCV directacting antiviral.

PCSK9 inhibitors for hypercholestro-laemia

Evolocumab, the first biologic drug for the treatment of hypercholesterolaemia, is set to launch in Europe following a positive opinion from the European Medicines Agency (EMA). It is the first monoclonal antibody for treating high cholesterol and the first inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) to be recommended for approval. Evolocumab provides a new option for people who are unable to control their cholesterol levels with current treatments such as statins and other lipid-lowering drugs. It is also an alternative therapy for people who are statin-intolerant. Late last month, the US FDA approved another PCSK9 inhibitor, alirocumab injection for the same indication as evolocumab. Alirocumab is approved for use in addition to diet and maximally tolerated statin therapy and still require additional lowering of LDL cholesterol. Alirocumab is marketed as Parulent® by Sanofi.

Newer contraceptive pills associated with higher risk of clots

Combined contraceptive pills containing one of the newer progestogens are associated with a higher risk of venous thromboembolism (VTE) than pills containing older progestogens, a study published in the BMJ on 26 May 2015 has found. The increased risk associated with combined oral contraceptives is well known, but previous studies have used different methods to examine this link, meaning the relative risks associated with different hormone combinations have been unclear. To address this, researchers from the University of Nottingham used prescription data from two large UK general practice databases to measure the associations between use of the different types of combined oral contraceptives and risk of VTE in women aged 15—49 years, adjusting for other known risk factors. A total of 1,340 practices were covered by the two databases from which 10,562 eligible VTE cases were identified and matched with 42,034 controls. The results showed that current users of any combined oral contraceptive had a threefold increased risk of VTE compared with non-users of similar age and health status (adjusted odds ratio 2.97, 95% CI 2.78— 3.17). When different pill combinations were looked at, women using combined pills containing older progestogens (Levonorgestrel, norethisterone and norgestimate) had around a two and a half times increased risk of VTE compared with women not using any form of pill, while women using pills containing newer progestogens (drospirenone, desogestrel, gestodene and cyproterone) had around a four times increased risk of VTE. In absolute terms, the number of extra VTE cases per year per 10,000 women was lowest for Levonorgestrel and norgestimate (6 extra cases), and highest for desogestrel and cyproterone (14 extra cases).

New treatment for schizophrenia and depression
Brexpiprazole tablets have been approved by the US FDA last month to treat adults with schizophrenia and as an add-on treatment to an anti-depressant medication to treat adults with major depressive disorder (MDD). The effectiveness of brexpiprazole in treating schizophrenia was evaluated in 1310 participants in two 6week clinical trials. Brexpiprazole was shown to reduce the occurrence of symptoms of schizophrenia compared to placebo. Its effectiveness as an add-on treatment for MDD was evaluated in two 6week trials that compared brexpiprazole plus an anti-depressant to placebo plus an anti-depressant in 1046 participants for whom anti-depressant alone did not adequately treat their symptoms. The participants taking brexpiprazole reported fewer symptoms of depression than those taking the placebo. Brexpiprazole and other drugs used to treat schizophrenia have a warning alerting health care professionals about an increased risk of death associated with the off-label use of these drugs to treat behavioral problems in older people with dementia related psychosis. No drug in this class is approved to treat patients with dementia related psychosis. The most common side effects reported by participants taking brexpiprazole in clinical trials included weight gain and inner sense of restlessness, such as feeling the need to move. Brexpiprazole is manufactured by Tokyo-based Otsuka Pharmaceutical Company Ltd. and is marketed as Rexulti®.

Sacubitril/valsartan combo for heart failure treatment
Early last month the US FDA approved sacubitril and valsartan combination tablets for the treatment of heart failure. Sacubitril acts by inhibiting the enzyme neprilysin. The combo was studied in a clinical trial of more than 8000 adults and was shown to reduce the rate of cardiovascular death and hospitalizations related to heart failure compared to enalapril. Most patients were also receiving currently approved heart failure treatments including beta-blockers, diuretics, and mineralocorticoid antagonists. The combo was reviewed under the FDA’s priority review program, which provides for expedited review of drugs that are intended to treat a serious disease or condition and may provide a significant improvement over available therapy. The most side effects in clinical trial participants treated with this combo were hypotension, hyperkalaemia and renal impairment. Sacubitril/valsartan combo is contra-indicated in pregnancy. If pregnancy is detected while on treatment, the drug should be discontinued as soon as possible. The drug is manufactured by Novartis, New Jersey and is marketed as as Entresto®.
“Angioedema was reported with sacubitril/valsartan; black patients and patients with a prior history of angioedema have a higher risk”

Source: CMC Pharmacy Bulletin, a publication of the Pharmacy Service (DISH), CMC, Vellore.


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Amith Balachandran, Department of Anaesthesia, CMC Vellore, and
Ashish Jacob Mathew, Assistant Professor, Department of Rheumatology, CMC, Vellore.


Systemic lupus erythematosus (SLE) is a disease with an auto-immune origin, which occurs nine times more often in women than in men, and is especially prevalent among women of the child bearing age group. Presence of autoantibodies against a person’s own proteins, which develop well before the diagnosis, is a hallmark of this disease. Patients present with variable clinical features ranging from mild joint and skin involvement to life-threatening renal, hematologic, or central nervous system involvement. This makes it a clinically heterogeneous entity which makes timely diagnosis challenging. It is only apt to include it in the group of the great mimics in medicine.

One of the major threats which increases the mortality risk in patients with SLE is the high rate of infections. Co-morbid illnesses like cardiovascular risk and treatment related complications, generally related to corticosteroid usage, always play a pivotal role in management of this disease. The first case of systemic lupus erythematosus from India was reported in 19551.Today SLE is one of the most commonly diagnosed autoimmune disorders, and newer clinical manifestations and immune phenomena are being studied and reported worldwide.


The preliminary criteria for classification of SLE was published in 1971,2,3 and was popularly known as the ARA (American Rheumatism Association) Criteria, which were then modified in 19824 (The ACR/American College of Rheumatology Criteria) and later in 19915 to include newer diagnostic modalities and immunological knowledge (Table 1). These were introduced to classify patients for research purposes and not as diagnostic criteria for SLE. Subsequently, multiple groups employed new statistical methodology to refine SLE classification criteria. However, the 1991 modification of ACR criteria remained the most popular, and despite being a classification criteria, has been widely used as a diagnostic tool for SLE.


Although it was widely popular, several concerns about the ACR criteria were being raised. The SLICC (Systemic Lupus International Collaborating Clinics) is an international research group that is over 30 years old, which is dedicated to SLE and has contributed much to this field, including development of the ACR/SLICC Damage Index6.

The SLICC noted the following concerns about the ACR criteria7

1) Concerns about many patients without any immunologic criteria being classified as SLE,

2) Duplication of highly correlated cutaneous lupus terms (malar rash and photosensitivity) and missing out on many other lupus cutaneous manifestations,

3) Many of the SLE specific neurologic manifestations were not included.

4) Quantification of urine protein had to be modified utilizing new standards,

5) Omission of low serum complement levels,

6) Inclusion of new knowledge on antiphospholipid antibodies in the immunologic criteria,

7) Patients with biopsy proven lupus nephritis may not be classified as SLE according to ACR criteria.

8) The 1997 revision of ACR criteria were not validated.

With the intention to improve the clinical relevance of the ACR criteria, they incorporated recent findings on the immunology of SLE and addressed several problems that were attributed to the 1982/1997 criteria. Along

with this, they performed the so far missing validation, giving rise to the SLICC criteria, which was initially published in 2012.

Table 1: A Comparison between the Classification Criteria for SLE

SLICC 2012

ACR 1997

ACR 1982

ARA 1971

1. Acute Cutaneous Lupus 1. Malar Rash 1. Malar Rash 1. Facial Erythema
2. Chronic Cutaneous Lupus 2. Discoid Rash 2. Discoid Rash 2. Discoid Lupus
3. Photosensitivity 3. Photosensitivity 3. Photosensitivity
3. Oral/Nasopharyngeal ulcers 4. Oral or Nasal Ulceration 4. Oral or Nasal Ulceration 4. Oral or Nasal Ulceration
4. Non-scarring alopecia 5. Alopecia
5. Synovitis involving > 2 joints 5. Non Erosive arthritis involving two or more joints 5. Non Erosive arthritis involving two or more joints, characterized by tenderness, swelling or effusion 6. Arthritis without Deformity
6. Serositis 6. Pleuritis or pericarditis 6. Serositis: pleuritis or pericarditis 7. Pleuritis or pericarditis
7. Renal manifestations 7. Renal disorder: persistent proteinuria or cellular casts 7. Renal disorder: persistent proteinuria or cellular casts 8. Cellular Casts
9. Proteinuria
10. Raynaud’s Phenomenon
8. Neurological manifestations 8. Neurologic disorder: seizures or psychosis 8. Neurologic disorder: seizures or psychosis in the absence of offending drugs or known metabolic derangement 11. Psychosis or Convulsions
9. Hemolytic anemia 9. Hematological Disorder
Hemolytic anemia



9. Hematological Disorder
Hemolytic anemia



12. Hemolytic anemia or
Lymphopenia or


10. Leucopenia/Lymphopenia
11. Thrombocytopenia
12. ANA 10. Positive antinuclear antibody by IFT or an equivalent assay 10. Positive antinuclear antibody by IFT or an equivalent assay 13. L.E. cells
13. Anti-dsDNA 11. Immunologic Disorder
– Anti-DNA antibody to native DNA
– Anti-Sm antibody

– Positive antiphospholipid antibodies:

a) IgG or IgM anticardiolipin

b) positive lupus anticoagulant (LA) or

c) false positive test for syphilis

11. Immunologic disorder
– Anti-DNA antibody
– Anti-Sm antibody

– Positive LE Preparation

– False positive test for syphilis

14. Chronic false positive test for syphilis
14. Anti-Sm
15. Anti Phospholipid Antibody
16. Low Complement
17. Direct Coombs Test

Table 2. The 2012 SLICC Classification Criteria for SLE

Classify a patient as having SLE if
a) The patient satisfies four of the criteria, including at least one clinical criterion and one immunologic criterion or
b) The patient has biopsy-proven nephritis compatible with SLE and with ANA or anti-dsDNA antibodies
1. Acute Cutaneous Lupus Lupus malar rash (do not count if malar discoid), Bullous lupus, Toxic epidermal necrolysis variant of SLE, Maculopapular lupus rash. Photosensitive lupus rash (in the absence of dermatomyositis). Subacute cutaneous lupus (nonindurated psoriaform and/or annular polycyclic lesions that resolve without scarring, occasionally with post-inflammatory dyspigmentation or telangiectasias)
2.Chronic Cutaneous
Classical discoid rash-localised (above the neck) or generalised (above and below the neck). Hypertrophic (verrucous)lupus.
Lupus panniculitis (profundus). Mucosal lupus. Lupus erythematosus tumidus, Chillblains lupus, Discoid Lupus-lichen planus overlap.
3.Oral ulcers Palate, Buccal, Tongue or Nasal ulcers (in the absence of other causes, such as vasculitis, Behcets, infection (herpes), IBD, reactive arthritis, and acidic foods)
4.Non-scarring alopecia Diffuse thinning or hair fragility with visible broken hairs (in the absence of other causes such as alopecia areata, drugs, iron deficiency and androgenic alopecia)
5.Synovitis involving >2 joints Characterized by swelling or effusion or tenderness in 2 or more joints and thirty minutes or more of morning stiffness.
6.Serositis Typical pleurisy for more than 1 day or pleural effusions or pleural rub.
Typical pericardial pain (pain with recumbency improved by sitting forward) for more than 1 day or pericardial effusion
Or pericardial rub or pericarditis by ECG (in the absence of other causes, such as infection, uremia, and Dressier’s pericarditis)
7.Renal manifestations Urine protein/creatinine (or 24 hr urine protein) representing 500 mg of protein in 24 hr or red blood cell casts
8.Neurological Manifestations Seizures, psychosis, Mononeuritis multiplex (in the absence of other known causes such as primary vasculitis), myelitis, peripheral or cranial neuropathy (in the absence of other known causes such as primary vasculitis, infection and diabetes mellitus), acute confusional state (in the absence of other causes, including toxic-metabolic, uremia, drug)
9.Hemolytic anemia
10.Leucopenia/ Lymphopenia Leucopenia <4000mm3 at least once (in the absence of other known causes such as Felty’s, drugs, and portal hypertension)
Lymphopenia <1000mm3 at least once (in the absence of other known causes such as corticosteroids, drugs and infection)
11.Thrombocytopenia <100,000mm3 at least once (in the absence of other known causes such as drugs, portal hypertension, and TTP)
1.ANA Above the reference range of the laboratory
2.Anti-dsDNA Above laboratory reference range, except ELISA: twice above laboratory reference range
4.Anti Phispholipid
Lupus anticoagulant, False positive RPR, Medium or high titre anticardiolipin (IgA, IgG or IgM) and beta 2-glycoprotein I (IgA, IgG or IgM)
5.Low Complement Low C3, C4 or CH50
6.Direct Coombs Test In the absence of haemolytic anemia
Criteria are cumulative and need not be present concurrently

Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin FR et. al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012.


The SLICC classification criteria were derived from a set of 702 expert-rated patient scenarios. After an initial review of the clinical manifestations of SLE, a short standardised narrative of 10-12 patients who had the clinical diagnoses of SLE and 10-12 controls, who had diagnoses of close differentials of SLE (like APLA, Scleroderma, Fibromyalgia) were sent to 32 rheumatologists, who were unaware of the diagnosis made by the primary physician. If >80% of these rheumatologists made a diagnosis of SLE it was considered as a consensus diagnosis. A subcommittee then used statistical tools to identify variables that significantly contributed to separation of SLE cases from others and summarised it into a simple classification rule. The rule was vigorously discussed in meetings and few changes made on the basis of voting by experts.

To validate the criteria, a different group of 690 patients diagnosed to have SLE were studied in a similar fashion, and their blood tested for immunological criteria in same standardised laboratory. Statistical methods were used to find out specificity and sensitivity of the SLCC criteria and compare it to the ACR criteria.


The classification criteria that thus emerged were published in 2012, and is popularly called the SLICC criteria (Table 2). It contains 11 clinical and 6 immunological criteria. The proposed classification rule is as follows:

Classify a patient as having SLE if

The patient satisfies four of the criteria, including at least one clinical criterion and one immunologic criterion.


The patient has biopsy-proven nephritis compatible with SLE and with ANA or anti-dsDNA antibodies.

Criteria need not be present concurrently.7

Some of the features of the SLICC classification:

1) Similar skin manifestations were grouped and discrete skin manifestations added as a new group.

2) Arthritis criterion was redefined so that it doesn’t require a radiograph, and can be diagnosed clinically

3) The renal criterion now includes measurement of proteinuria by the urine protein/creatinine ratio without the requirement of a time frame for collection. This reflects acceptance that the “spot” or random urine protein/creatinine ratio is easier to obtain than a 24 hour urine protein

4) Several new established neurological manifestations (other than Seizures and Psychosis) were included

5) Each Hematological manifestation was given more weightage

6) The immunologic criterion reflects new knowledge about serologic tests in SLE and each criterion now gets more weightage as compared to the ARA criteria, where all the immunological tests were grouped into one criterion

7) Patients with Biopsy proven Lupus (according to Nephritis International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Classification of Lupus Nephritis8) can now be classified as SLE, in the presence of one immunological variable.

However, whether the SLICC criteria is really superior to ACR criteria in a real life clinical setting in terms of picking up more cases early and avoiding false diagnoses needs to be carefully studied before we can replace one with the other.

Observations from studies:

The following are some significant observations from various studies.

1) In the validation sample the SLICC classification criteria misclassified fewer cases and had higher sensitivity, although less specificity. The difference between the ACR classification criteria and SLICC classification criteria performance was however not statistically significant. (Table 3)

2) In a study that applied the SLICC criteria to 2 large multi-ethnic cohorts, it was noted that when compared to the judgment of expert physicians, SLICC criteria allowed the earlier diagnosis of a sizable proportion of patients who, otherwise, could not be identified until later with the consequent beneficial implications. However the authors raises the distinct possibility that some patients could not be identified until later using the SLICC criteria, and some, not at all.9

3) In a retrospective analysis of childhood onset SLE involving 3 main pediatric lupus centers both sets of classification criteria were analyzed in 154 childhood SLE patients with a mean age at disease onset of 12.7 years and in 123 controls with a mean age of 8.9 years. The sensitivity and specificity of the ACR criteria were 76.6% and 93.4%, respectively, whereas those of the SLICC criteria were 98.7% and 85.3%, respectively. It was noteworthy that 22 lupus nephritis patients failed to meet four of the ACR criteria. The SLICC criteria showed better sensitivity (p<0.001) and led to fewer misclassifications, but were less specific (p<0.001) than the ACR criteria10

4) In a cross sectional study of 110 SLE patients from Croatia, a moderate correlation between the number of SLICC classification criteria and SLEDAI disease activity index was found, both in active and inactive disease. However, there was no correlation between the number of ACR classification criteria and disease activity index. SLICC classification criteria correlate with disease activity because they capture more clinical and laboratory findings also involved in SLEDAI index. More patients satisfied the neurological and hematological criteria in SLICC than in the ACR criteria.11

5) In a Swedish study SLICC-12 showed a diagnostic sensitivity of 94% compared with90% (for the updated set of ACR criteria from 1997, whereas ACR-82 failed to identify every fifth true SLE case. However, the disease specificity of SLICC-12 reached only 74%.12


1. Malaviya et al. Systemic lupus erythematosus in India. Lupus; 1997;6(9):690-700.

2 . Cohen, A. S., et al., Bulletin on Rheumatic Diseases, 1971,

3. Davis et al. Criteria for Classification of S.L.E. British Medical Journal, 1973 Jul 14;3(5871):88-9.

4. Tan et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum; 1982.

5. Hochberg M C et al. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997 Sep;40(9):1725.

6. Gladmann et al. The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index for Systemic Lupus Erythematosus International Comparison. J Rheumatol. 2000;Feb;27(2):373-6.

7. Petri et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012 Aug;64(8):2677-86. doi: 10.1002/art.34473.

8. Weening et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney International. 2004 Feb;65(2):521-30.

9. Pons-Estel et al. The American College of Rheumatology and the SystemicLupus International Collaborating Clinics Classification criteria or systemic lupus erythematosus in two multi-ethnic cohorts: a commentary. Lupus 2014;23(1):3-9. doi: 10.1177/0961203313512883. Epub 2013 Nov 27,

10. Sag et al. Performance of the new SLICC classification criteria in childhood systemic lupus erythematosus: a multicentre study. Clin Exp Rheumatol. 2014 May-Jun;32(3):440-4. Epub 2014 Mar 17.

11. Felina Anić et al. New classification criteria for systemic lupus erythematosus correlate with disease activity. Croat Med J. 2014 Oct;55(5):514-9.

12. Ighe et al. Application of the 2012 Systemic Lupus International Collaborating Clinics classification criteria to patients in a regional Swedish systemic lupus erythematosus register. Arthritis Research & Therapy 2015 Jan 10;17(1):3. doi: 10.1186/s13075-015-0521-9.

Chronic venous ulcer

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An update on Venous Disease

– Chronic Venous Ulcer

Indrani Sen, Assistant Professor, Department of Vascular Surgery, Christian Medical College, Vellore.


A chronic venous leg ulcer is an ulcer occurring in a patient with venous disease that remains unhealed for at least four weeks. It is the most common cause of chronic leg ulceration and poses a significant socioeconomic burden on those who develop the illness. Though the pathophysiology is not very clear it is suggested that venous incompetence and associated venous hypertension contribute to the mechanism of venous ulceration. A systematic history and examination of the patient will help identify factors that may help in diagnosis, treatment and prognosis. Conservative management with compression (elastic compression stocking/bandage), ankle exercises, dressings and foot elevation is the mainstay of management. Of these compression is the most important. Healing time varies with some ulcers taking up to one year to heal. Almost all venous ulcers recur unless the superficial reflux is treated. Most patients with chronic venous ulceration will benefit from the addition of simple venous surgery. Patients with superficial venous reflux should therefore be considered for superficial venous surgery to prevent recurrence.


The most common cause of chronic leg ulceration is venous disease and it affects about 1% of the population1. A leg ulcer that does not heal is associated with significant socioeconomic burden resulting in an impaired quality of life. Proper management is therefore of critical importance to prevent chronic disability that may result from this easily treatable condition. There are multiple Western treatment guidelines and these can be extrapolated and tailored to the Indian context.

Its prevalence is thought to increase with age; however ulceration is not restricted to the elderly. A large proportion of those affected are young. Some of the factors that affect prognosis are the patient’s psychosocial and economic state, occupation, mobility, ease of access to health care and motivation for continuing home treatment. These are factors that need to be assessed and optimised, based on individual needs, to ensure the best chance for healing. The treatment between non-specialist and dedicated vein clinics varies, with the latter achieving higher ulcer healing and lower recurrence rates.


A chronic venous leg ulcer is an ulcer occurring in a patient with venous disease that remains unhealed for at least four weeks.

Though the pathophysiology is not very clear it is suggested that venous incompetence and associated venous hypertension contribute to the mechanism of venous ulceration. Primary varicose veins or deep vein thrombosis causes valve incompetence and calf muscle pump insufficiency. This in turn produces ambulant venous hypertension which leads to microcirculatory changes and tissue ischemia resulting in recurrent chronic venous leg ulceration.2

In the following sections we briefly go over the clinical presentation and detail the management protocol based on current guidelines for a patient presenting with a chronic venous ulcer.

Clinical evaluation

History – Some of the important pieces of information to be elicited and documented are given below.

  • Details of onset and progression.
  • Previous history of deep vein thrombosis and its treatment along with any relevant family history.
  • In women, menstrual and obstetric history to document the relation of varicose veins or edema to pregnancy, use of hormone therapy etc.
  • Details of occupation and lifestyle along with a ‘Quality of Life’ (QOL) assessment provide useful information to guide treatment options.
  • Drug and medical history should be elicited: patients may present with ulceration secondary to a drug reaction, vasculitis, diabetes or in certain haematological disorders like haemosiderosis or sickle cell disease.


  • Examination of the distribution of varicose veins (standing position), edema, skin changes, and sites of healed or active ulceration should be performed and documented. (See Fig.2 on page 67)
  • The skin should be examined for erythema, weeping, scaling and pigmentation to differentiate venous eczema from contact/allergic dermatitis.
  • The depth and the fixity of ulcers to underlying structures should be assessed. If possible, serial measurement of the surface area should be done.
  • Non-venous causes of edema (liver, thyroid, heart, and kidney disease / drug history) should be ruled out. A complete arterial history and examination with measurement of the ankle brachial pressure index (ABPI) should be performed.
  • The body mass index should be calculated.
  • Assessment of joint mobility, presence of infection, groin node enlargement, atypical features (multiple, necrotic, deep: s/o vasculitis; rolled out edges s/o malignancy; undermined margin s/o tuberculosis), neuropathy and lymphedema along with a systemic examination should be performed.
  • Look for concomitant obesity, peripheral arterial disease (seen in 22% of cases), rheumatoid arthritis/ systemic vasculitis in (9% of cases), pyoderma gangrenosum, diabetes mellitus (seen in 5% of cases) or other coexistent medical illness that may complicate the course of treatment. Pointers to these conditions should be looked for in the clinical examination and ruled out by directed tests when suspected. Consider referral to Dermatology, Rheumatology or Endocrinology if any of the above problems are encountered.
  • Continuous reassessment of healing, etiology, co morbidities and compliance should be carried out at each visit to ensure that the management is consistent and appropriate.

Fig. 2a: Varicose veins

Fig 2b: Venous ulcer in the lower limb. Notice the discolouration of the skin surrounding the ulcer


  • A venous duplex is the first line of investigation.
  • Blood tests to rule out systemic disorders should be done when indicated after clinical examination. These are listed in Table 1.
  • Grossly infected/ atypical/ cellulitic ulcers may need microbiological tests (pus/tissue culture) and biopsy may be needed to rule out vasculitis and malignancy.
Table 1. Investigations

Full blood count




Serum Albumin, liver enzymes


Blood sugar


Serum urea, creatinine

and electrolytes


Thyroid stimulating hormone


D dimer, venous duplex




ECG, ECHO, Chest X ray


Abdominal/ pelvic imaging


The diagnostic protocol used for patients with venous ulcers is presented in Fig. 1. Duplex ultrasound is the first line of imaging. Evaluation of the deep veins and other tests for hemodynamic assessment are performed in patients with recalcitrant symptoms and no demonstrable abnormality on duplex ultrasound.

Figure 1: Evaluation and management of CV

Basic CEAP Classification
Clinical Classification:
C 0
C 1
C 2
C 3

C 4a
C 4b

C 5

C 6


No visible evidence of venous disease
Superficial spider veins (telangectasias or reticular veins)
Simple varicose veins only
Ankle edema of venous origin

Skin pigmentation in the ankle area and/or dermatitis/eczema

Healed venous ulcer

Open (active) venous ulcer


Etiologic classification

No venous etiology

Anatomic classification

Superficial veins
Perforating veins
Deep veins
No venous anatomy involved

Pathophysiology classification

Reflux and obstruction
No venous pathology

CEAP = Clinical-Etiologic- Anatomic-Pathophysiology.
Modified from Meissner et al. J Vasc Surg.2007:4 (suppl. S)54S-67S.


Bisgaards regimen – This remains the mainstay of treatment for ulcer healing. This is combined with complex decongestive therapy (manual lymphatic drainage) to reduce edema and over a period of time reduce the ankle fibrosis to a certain extent. Mobility of the ankle is important for activity of the calf muscle pump- a fixed ankle often hinders the healing process.

There are 4 components in this regimen: compression, ankle exercises, dressings and bed rest with foot elevation)

1. Ankle exercises: Range of motion exercises for the ankle dorsiflexion and plantar flexion of the ankle joint is what is essential to activate the calf pump. Movement of only the toes is NOT adequate.

2. Dressings: The wound will need daily or twice daily dressings depending on the amount of discharge and debridement of slough will be required periodically. The type of dressing applied has no effect on accelerating wound healing- even a simple saline dressing that facilitates moist wound healing is adequate.

3. Rest and foot elevation: Elevation of the limb on two pillows or the foot end of the bed on a 4-6inch bloc is advisable. Patients who are obese or have concomitant cardiac disease may not tolerate elevation very well.

    4. Compression: Of the four components, compression is the main component that promotes healing– this can be done by bandages, stockings or pneumatic compression devices. Compression should be avoided in patients with an ABPI of < 0.8. Though seemingly simple, it does have potential for increased skin damage if the pressures are too high, and should be used with caution in patients with diabetes or fragile skin.

Other than the traditional elastic bandages; multi or single component elastic, extensible or inelastic (short stretch) compression bandages are also available. The multi-component (4 layer bandages) provide the highest sustained pressure for a longer time. This is available as a commercial kit or can be assembled from individual components. However, all the components cannot be reused. Overall, this is a more expensive option but this avoids daily dressings and is cost effective in patients with large wounds. A meta-analysis of RCTs comparing 4 layer bandages (4LB) with short stretch bandage found that the 4LB was associated with a significantly shorter time to healing.3

Graduated compression stockings: These are available in different sizes, lengths, material, designs and compression/class which vary between manufacturers. They can be custom-made for patients who do not match the available sizes. These provide the maximum pressure at the ankle: Class 1: 14–17 mmHg , class 2: 18–24 mmHg, class 3: 25–35 mmHg, class 4 : 49–70 mmHg: Class 2 stockings are prescribed for ulcer disease. A meta-analysis of eight RCTs concluded that compression with stockings is more effective than bandages. Patients are advised the strongest compression to which they can comply.3

Intermittent pneumatic compression:
Eight or 12-chamber pneumatic compression devices are also available for use in ulcer disease. These can provide a gradual increase in the compression pressure which is useful in patients who find the sudden application of higher pressures painful or uncomfortable. This is mostly restricted to hospital use. Affluent patients who require lifelong therapy may opt to buy a machine for home use.

Patient preference, lifestyle, compliance, required frequency of application, size and shape of the leg are some factors which guide the specific modality chosen in a particular patient. Adjuncts like analgesics and antibiotics are prescribed when indicated

Other interventions:

About 30% of ulcers do not heal in a year. Two drugs, Daflon (micronized purified flavonoid fraction) and Trental (pentoxifylline) have shown benefit in ulcer healing by favourably altering the rheological venolymphotonic microcirculation. Many pharmaco-mechanical adjuncts e.g. low dose diuretics, steroids, aspirin, zinc/vitamin supplements, topical antibiotics, growth factors, honey, acupuncture, electromagnetic therapy, hyperbaric oxygen, infrared light/ laser, ultrasound therapy and skin substitutes have been studied. None of these have been proven to cause dramatic improvement and there is insufficient evidence to recommend their use.

Prevention of recurrence

Almost all venous ulcers recur unless the superficial reflux is treated. A below-knee graduated compression stocking is recommended to prevent recurrence after ulcer healing has been achieved. The ESCHAR trial randomised to either compression treatment alone or compression in combination with superficial venous surgery showed that surgical correction of superficial venous reflux reduces 12-month ulcer recurrence. Most patients with chronic venous ulceration will benefit from the addition of simple venous surgery. (12% versus 28%, hazard -2.76 (95% CI -1.78 to-4.27). Surgery however did not improve ulcer healing rates. Patients with superficial venous reflux should therefore be considered for superficial venous surgery to prevent recurrence.4

Open surgery (Trendlenberg high tie, stripping and stab avulsion), heat ablation using radiofrequency or laser is available in India; other modalities like glue, superheated steam etc. are under study but not yet approved for clinical use. The latter is a relatively newer modality-long term outcomes specific to ulcer disease are not available. However, its use is recommended based on early studies which demonstrate marginally better immediate postoperative recovery. Other modalities like foam sclerotherapy have a role in treatment of perforator incompetence.

Even with the above treatment, about 5% ulcers will recur in 5 years. Repeat imaging to rule our recurrent varicose veins is done and if recurrence is found, it is treated on the same lines as primary disease. Reflux or obstruction in the deep veins is assessed. Stenting of an obstructed deep venous segment or venous valve repairs have a role in ulcer healing and reduction of edema in symptomatic patients. Valvuloplasty, valve transposition or valve transplant are offered for patients with isolated deep venous reflux.

Last but not the least are rarer conditions like congenital varicose veins (Klippel-Tenaunay syndrome) or arteriovenous fistulae presenting with ulceration due to secondary CVI. These usually have characteristic clinical findings like local gigantism, leg length discrepancy, lateral varicose veins and abnormal pulsatile venous flow. These patients need more extensive imaging (MRI/ Angiogram) and referral to a specialist vascular center for further management.

         Though venous ulcers have been known since antiquity, the cause of their chronicity and pathophysiology are still incompletely understood. Treatment options are varied- these need to be tailored to the individual’s needs. Conservative management with compression, ankle exercises, dressings and foot elevation is the mainstay of management. Of these compression is the most important. Compression increases ulcer healing rates compared with no compression. An elastic bandage is more effective than inelastic bandages.
      Historically, patients with large chronic ulcers were sometimes advised amputation but this is largely unnecessary with current treatment modalities. Most ulcers heal and do not recur if treated early.


  1. O’Meara S, Al-Kurdi D, Ologun Y, Ovington LG, Martyn-St James M, Richardson R. Antibiotics and antiseptics for venous leg ulcers. Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No.: CD003557.
  2. de Araujo T, Valencia I, Federman DG, Kirsner RS. Managing the patient with venous ulcers. Ann Intern Med. 2003;138(4):326–334.
  3. O’Meara SCullum NNelson EADumville JC. Compression for venous leg ulcers. Cochrane Database Syst Rev. 2012 Nov 14;11:CD000265. doi: 10.1002/14651858.CD000265.pub3.
  4. Barwell JRDavies CEDeacon JHarvey KMinor JSassano ATaylor MUsher JWakely CEarnshaw JJHeather BPMitchell DCWhyman MRPoskitt KR. Comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR study): randomised controlled trial. Lancet. 2004 Jun 5;363(9424):1854-9.


Electronic cigarette – evidence update

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Evidence Update

Summary of a Cochrane Review

Electronic cigarettes: Are they effective in smoking cessation and reduction?

Conclusion: Electronic cigarettes can possibly help smokers stop and also reduce their cigarette consumption

Researchers in The Cochrane Collaboration conducted a systematic review on the effects of electronic cigarettes on smoking cessation and reduction. After searching through relevant databases, two randomized controlled trials were identified that together enrolled over 600 adults. This Evidence Update summarizes the key findings. This Evidence Update summarizes the key findings.

Electronic Cigarettes and smoking cessation

What are electronic cigarettes?

Electronic cigarettes (EC) also known as e-cigarettes are battery operated devices made to resemble regular tobacco cigarettes. Although e-cigarettes have been available in the market for a few years, their popularity has increased considerably in recent times.

ECs do not contain tobacco and do not emit smoke however they contain nicotine, thereby providing smokers with the nicotine ‘rush’ without exposing them or others to the smoke of regular cigarettes.

EC manufacturers claim that they are a safer substitute for regular cigarettes, however, the benefits and risks have been widely debated.

Smoking cessation attributes to multiple health benefits. However, most smokers despite the desire to stop smoking are unable to, and often resort to medical help or behavioural support.

Despite this additional support, the long-term quit rates among smokers is low and ECs might prove beneficial in overcoming this.

What does research say?

The review compared

(i) nicotine ECs with nicotine-free EC (placebo)

(ii) nicotine ECs with nicotine patches

It was found that :

· Nicotine EC users were more likely to stop smoking when compared to placebo EC users

· Nicotine ECs were more effective than placebo ECs and nicotine patches in achieving 50 % or more smoking reduction, this was supported by low quality evidence

How confident can I be of this evidence?

Although the two studies included in the review were rated as low risk of bias, the overall evidence was graded as low because the total number of participants included in the studies was only approximately 660. Hence the results should be interpreted with caution. Data from ongoing trials might change these conclusions in future updates.

Can this evidence be applied in my setting?

The studies included in the review were conducted in Italy and New Zealand where ECs are easily available and affordable. Therefore this evidence may not be directly applicable to low and middle income countries

Electronic cigarettes for smoking cessation and reduction

This table provides more detail about the effectiveness of ECs on smoking cessation and reduction These numbers are based on research findings that are currently available. The quality of evidence is rated as high, moderate, low or very low.

Nicotine EC No. of participants What happens Quality of evidence
Cessation: Nicotine EC versus placebo EC
(Follow-up : 6-12 months)
40 per 1000 93 per 1000
(42 –201)
(2 studies)
Slightly higher rates of cessation were noted in the Nicotine EC group Low
Cessation: Nicotine EC versus nicotine replacement therapy
(Follow-up :6 months)
58 per 1000 73 per 1000
(1 study)
It is uncertain if cessation rates differs between both groups Very low
Reduction: Nicotine EC versus placebo EC
≥ 50% reduction in baseline
cigarette consumption

(Follow-up: 6 – 12 months)

271 per 1000 355 per 1000
(277 –455)
(2 studies)
Reduction rates in Nicotine EC user was found to be slightly better than in placebo EC user Low
Reduction: Nicotine EC versus nicotine replacement therapy
≥ 50% reduction in baseline
cigarette consumption

(Follow-up: 6 months)

* Does not include quitters

435 per 1000 614 per 1000
(1 study)
Higher proportion of EC users achieved 50% or more reduction Very low

More information

This summary is based on the following systematic review:
McRobbie H, Bullen C, Hartmann-Boyce J, Hajek P. Electronic cigarettes for smoking cessation and reduction. Cochrane Database of Systematic Reviews 2014, Issue 12. Art. No.: CD010216. DOI: 10.1002/14651858.CD010216.pub2

What is a systematic review?
A systematic review seeks to answer a well formulated and specific question by identifying, critically appraising, and summarising the results of all relevant trials, published and unpublished, according to pre-stated and transparent methods.

What is the Cochrane Collaboration?
The Cochrane Collaboration is an international network of more than 28,000 people from over 100 countries. The collaboration is one of the biggest producers of systematic reviews on the effects of healthcare interventions, and Cochrane Systematic Reviews are recognized internationally as the benchmark for high quality information. The Cochrane Database of Systematic Reviews is available from and free for eligible countries.

How has the quality of evidence been assessed?
The quality of evidence has been assessed using methods developed by the GRADE working group ( The GRADE system considers ‘quality’ to be a judgment of the extent to which we can be confident that the estimates of effect are correct. The level of ‘quality’ is judged on a 4-point scale. Evidence from randomized controlled studies is initially graded as HIGH and downgraded by one, two or three levels after full consideration of : the risk of bias of the studies, the directness (or applicability) of the evidence, and the consistency and precision of the results.

High: Further research is very unlikely to change our confidence in the estimate of effect.

Moderate: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Low: Further research is very likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Very low: We are very uncertain about the estimate

Evidence update – Deworming

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Evidence Update

Summary of a Cochrane Review                 Child Health Series

In areas where intestinal worm infection is common, does giving school children deworming drugs improve health and school performance?

Deworming programmes have little or no effect on average weight gain, haemoglobin, height, cognitive ability, school performance, and mortality, even in high endemic are There is not enough evidence to know if deworming improves school attendance.

Cochrane researchers conducted a review of the effects of school -based deworming programmes onchildren’s health, ability to learn, and school attendance. After searching for relevant studies, they identified 44 trials enrolling 67,672 children, and one additional trial of over one million children.

What are deworming programmes and how might they work?

Soil-transmitted worms, including roundworms, hookworms, and whipworms, are common in tropical and subtropical areas, and particularly affect children in low-income areas where there is inadequate sanitation. Heavy worm infection is associated with malnutrition, poor growth, and anaemia in children. The World Health Organization currently recommends that school children in endemic areas are regularly treated with drugs which kill these worms. The recommended drugs are effective at greatly reducing worm infections, but the programmes are often promoted on the basis of additional benefits on child nutrition, growth, school attendance and performance, It is important to know whether these additional benefits will be gained, as they influence policy decisions about how money is spent, and potentially prevent investment in other interventions to address the wider problems of nutrition and school attendance.

Review edition

This review was updated in July 2015 and includes a trial of one million children from India and new information from the replication of a trial from Kenya that examined school attendance.

What does the research say?

Deworming programmes that treat all school children at regular intervals:
May have little/no effect on average weight gain.
May have little/no effect on average haemoglobin.
Probably has little/no effect on cognitive ability or exam performance.
We don’t know whether deworming improves school attendance.

How much certainty can I have in these results?

We have low certainty in the finding of no effect on weight and haemoglobin because of potential bias in the study methods and some inconsistency in the results between trials. We have moderate certainty in the finding of no effect on cognitive ability and exam performance. We are very uncertain whether there is an effect on school attendance due to the limited settings where this has been assessed and the risk of bias of the few studies that have been done.

Can the results of the research be applied to my setting?

Deworming programmes have not demonstrated consistent benefits in any setting, including those with high worm prevalence (15 trials), medium prevalence (12 trials), and low prevalence (10 trials). Three trials from 15 years ago did suggest important effects on weight gain, but trials published since then have not confirmed these findings.

The effects of school deworming programmes in areas where worm infection is common

This table provides more detail about what happens when school children are routinely treated with deworming drugs at regular intervals, and are followed up for more than one year, as this provides the best evaluation of what current policy aims to achieve. These numbers are based on the results of the research, when available. The certainty in the evidence is either ranked as high, moderate, low, or very low.

More information

No deworming programme

The mean weight gain ranged from 1.2 kg to 4.73 kg

The mean change in haemoglobin ranged from 0.26 to 1.75 g/dL

Deworming programme (95% CI)

The mean weight gain with deworming was 0.08 kg more (from 0.11 kg less to 0.27 kg more)

The mean haemoglobin with de-worming was 0.02 g/dL higher (0.08 g/d Lower to 0.04 g/dL higher) – None of the trials reported a benefit of deworming across multiple tests The mean school attendance ranged from 66% to 90%. The mean school attendance with de-worming was 2% higher (4% lower to 8% higher) Deaths in children 27 per 1000 25 per 1000 1,005,135.

This summary is based on the following open access Cochrane systematic review:
Taylor-Robinson DC, Maayan N, Soares-Weiser K, Donegan S, Garner P. Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin, and school performance. Cochrane Database of Systematic Reviews 2015, Issue 7. Art. No.: CD000371. DOI: 10.1002/14651858.CD000371.pub6

What is a systematic review?
A systematic review seeks to answer a well formulated and specific question by identifying, critically appraising, and summarising the results of all relevant trials, published and unpublished, according to pre-stated and transparent methods.

What is Cochrane?
Cochrane is an international network of more than 28,000 people from over 100 countries. The collaboration is one of the biggest producers of systematic reviews on the effects of healthcare interventions, and Cochrane Systematic Reviews are recognized internationally as the benchmark for high quality information. The Cochrane Database of Systematic Reviews is available from and free for eligible countries.

How has the certainty in the evidence been assessed?
The certainty in the evidence has been assessed using methods developed by the GRADE working group ( The level of certainty is judged on a 4-point scale. Evidence from randomized controlled studies is initially graded as high and downgraded by one, two, or three levels after full consideration of: the risk of bias of the studies, the directness (or applicability) of the evidence, and the consistency and precision of the results.

High: We are very certain that the true effect lies close to that of the estimate of the effect.

Moderate: We are moderately certain in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

Low: Our certainty in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.

Very Low: We have very little certainty in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

Evidence Update published in August 2015. Evidence Updates can be distributed free of charge.

The full review is available from


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TINY PRINTS – struggle for life

 Dr. Shafini Beryl , Junior medical officer , Baptist Christian Hospital, Tezpur, Assam.

This is the story of a baby born severely premature and her struggle to compete for existence, to prove herself fit to be fittest for survival. Kick up your feet and keep reading. This child is a miracle.

The baby was bought to our hospital in the afternoon on a busy day. The casualty medical officer was busy with all the severely ill patients; this baby suddenly caught his eye as she was brought into the room. He was shocked to see such a tiny baby. The baby was brought from 200 kms away, by road, after being denied admission in every hospital along the way. This was their last hope; the parents were not ready to push any further. The baby, she came 3 months early, straining the limits of what is possible and what is right. The baby was 24 weeks old and weighed a meager 900 gms. When a baby is born at the edge of viability, which is the greater act of love: to save him, or to say good-bye! The medical officer gave the option to take the child to the higher centre, Guwahati which was another 250 km away. The tired, worn out parents losing hope said they cannot go any further. So taking the chances, the medical officer admitted the baby in our nursery.

Some babies are born so early that they are beyond rescue. Other babies ripen in the womb into the third trimester but arrive a little early. In between those scenarios is a zone between life and death, between viability and futility. In the hands of experienced specialists, though, babies born slightly earlier may have a chance at survival. Babies born at 23 weeks may survive with these specialists in a state-of-the-art NICU, but the odds of survival are much lower. The earliest baby to have ever survived premature birth was born at 21 weeks and 6 days, and this was reported in the news as having been a “miracle.”But they spent nearly 2.4 million dollars on that baby.

The odds of survival increase as the pregnancy progresses, and even an extra week in the womb can make a difference. In general, premature babies born closer to 37 weeks will be much better off than those born before 28 weeks.

So the survival chance for our baby was about 50% with the best care possible. And we did not have incubators, mechanical ventilators preterm nutrition or pediatric surgeons or. But we planned on doing the best for the baby. The child stayed in the nursery for 10 days. She was adequately warmed and her mother was taught how to give kangaroo mother care (See box 1). Initially she was only on IV fluids and then cautiously after 5 days nasogastric feeding was started till the baby was able to tolerate the full feeds. Although the weight fell to 700 gm during her hospital stay, she started gaining weight toward the discharge. The parents wanted to take the baby home by day 10 as they were daily wagers and had no money. The mother was taught to give nasogastric feeds with adequate hygiene and kangaroo care for warmth and the baby was discharged.

The parents were unable to bear the hospital expenses and so the entire bill was written off by the hospital.

The baby was reviewed after a month and she now weighed 1.8 kg, was able to suck well and so, breastfeeding was initiated and the child was called 2 weeks later for immunization.


This incident happened in July, 2015.Since then we have been receiving a lot of preterm, low birth weight babies who are referred, even from our nearby government medical college.

And it is so humbling to see how GOD takes cares of these preemies that He has never let even one die during the hospital stay. The odds of them dying of other illness, becoming disabled are still there, and for this reason they are asked to review every month for developmental assessment.

    Baptist Christian Hospital (BCH), Tezpur, Assam is where this story unfolded. Assam, the state of beautiful tea gardens does not boast itself as having good health services. The health services are poor, quality compromised, quacks practicing and access to proper health care is even considered a boon by many. BCH provides health services to the nearby districts and states. We, as a unified team, want to touch the lives of forgotten people, heal the wounded and give hope to the weary. We strive to bring the love of Christ to the people in a way that makes a real difference in their lives. The joy that comes from this surpasses anything that money can buy!



1. Kliegman RM, Behrman RE, Jenson HB, Stanton BF, editors. Nelson Textbook of Paediatrics.18th edition. Philadelphia: Saunders Elsevier; 2007.


4. of fetal viability and its enhancement. Breborowicz GH1.


6. Conde-Agudelo A, Díaz-Rossello JL. Kangaroo mother care to reduce morbidity and mortality in low birthweight infants. Cochrane Database of Systematic Reviews 2014, Issue 4. Art. No.: CD002771. DOI: 10.1002/14651858.CD002771.pub3

Community mental health

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Birth of a community mental health project in a rural mission hospital

Johann Ebenezer MBBS, DPM, MD (Psych), Psychiatrist, Padhar Hospital


Mental health is often not considered a priority area in rural centres and mission hospitals. A widespread misconception exists, even among medical professionals that these disorders are rare, difficult to diagnose and expensive to treat. In this article we challenge these assumptions and describe the birth and development of a Community Mental Health project at Padhar Hospital, a Lutheran mission hospital in Madhya Pradesh over the past one year. The purpose of this article is to illustrate that effective community mental health intervention programs are not only essential in rural mission hospital settings, but also incredibly cost-effective in terms of financial and human resources.

Two stories: (Names have been changed to protect identity)

  1. Goddess in human form
    Priya, the second daughter of a teaching assistant in a primary school, was a normal, cheerful and playful little girl in a village primarily consisting of Gond tribals. She developed normally till about 5 years of age, and her parents reported that she could recite the alphabets in English and Hindi, and was capable of identifying pictures in books and was toilet trained fairly well. When she was three years old, she started having attacks of epilepsy. Due to the superstitious belief system prevalent among the village elders, the community believed that these attacks came because she was a goddess in human form and possessed supernatural powers. As a result of these beliefs, she was never treated. The frequency of seizures gradually increased and on one particular day when she was 5 years old, she had up to 15 attacks within a few hours. Following that, she became developmentally retarded, and has remained so ever since. She also developed hyperactivity associated with repetitive stereotypical movements and speech. Her speech now consisted only of one or two bi-syllabic words. She was completely dependent on her parents for all self care, soiling her clothes up to ten or fifteen times a day, and having erratic mealtimes. She also developed aggressive behaviour towards herself and others in response to various stimuli.

2.    Demon-possessed

Dhanush was a regular student and appeared to have a bright future. While he was preparing for his tenth standard examinations, a profound and sudden change overcame him. He did not appear for his exams. He started roaming around aimlessly and undressing himself in public and hit people with stones. His family members tied him up with iron chains in their house. He started withdrawing from everybody and even neglected his personal hygiene and care. He was taken to a private doctor for treatment but his condition remained the same. He was taken to several religious places as well and they met several sages and witchcraft practitioners. This state of affairs went on for about four years. As per the rural belief systems prevailing in the local area, he was considered as being possessed by a demon.
(‘Two stories’ – continued at the end of the article)


Mental, neurological, and substance use disorders account for 13% of the total global burden of disease. In low and middle income countries, 76% – 85% of people with severe mental disorders do not receive any treatment.[1]

As per the National Mental Health Program in India, the median prevalence of mental disorders is 65.4 / 1000 individuals at any given time. This translates into nearly 70 million individuals across the country currently requiring mental health interventions – an amount almost equal to the entire population of Germany, Europe’s most populous country. [2] To tackle this immense burden, there are currently only 0.3 psychiatrists for every 100,000 people in India[3], which is a total of less than 4000 for the entire country. 75% of these psychiatrists work in urban areas, where less than 40% of the population lives.[4,[5] Whole districts exist without a single trained mental health professional. No other medical specialty in India has such a mismatch between need and available human resources.

Padhar Hospital, Mental health scenario in Madhya Pradesh

Padhar Hospital is a 200 bedded multispecialty Lutheran mission hospital located in Betul district of southern Madhya Pradesh. The hospital started a Psychiatry department in June 2014, which is the first and only full-time mental health service in Betul district and in at least three other surrounding districts in a radius of more than 200 kms. The department currently consists of only one psychiatrist, myself. I soon realized that most of the patients who were coming to the psychiatry OPD, as well as our inpatients and consults from other departments were predominantly from urban areas, with hardly any hailing from the surrounding villages. This initially struck me as very odd, as I had a very different experience during my training years at Vellore, where large numbers of local people (even those from rural areas) made use of the mental health facilities. Although it was surprising for me then, I soon realized that most of the available literature, reports very similar situations across Central and Northern India, especially in states like Madhya Pradesh, where mental health facilities are not only inaccessible, but, for the most part, completely non-existent.

The majority of these areas around Padhar are poverty-stricken, primarily agrarian villages, and many are situated in areas with very limited accessibility by road with negligible public transport facilities. The population is multi-ethnic (with tribals such as the Gonds and Korkus besides the local Hindi-speaking population, as well as a sizeable Marathi-speaking population and even ethnic Bengalis – who migrated as refugees during the 1971 Indo-Pak war). There is also considerable religious diversity – although Hindus are a clear majority, there is a large Christian minority centered around Padhar Hospital, and a smaller Muslim minority as well. Many tribals practice a primitive form of religion with strong animistic belief systems and practices.

Mental illnesses and epilepsy are looked at in these remote communities with a mixture of fear and awe. Patients are either revered as incarnate deities or shunned as demon-possessed souls. Diverse magical exorcism rites from potions and local remedies to harsh beatings or branding with hot iron rods are common and are done at great financial cost to the families. Families of these hapless souls also face social ostracism, often being excluded from public functions. Surprisingly, these beliefs and practices are not confined to patients with dramatic conditions like schizophrenia and epilepsy, but also to people who suffer from common conditions like depression, anxiety and migraine, and face many of the same issues of stigma, ignorance and lack of treatment as those with more severe disorders.

Realizing that very few rural patients were coming to the hospital, I decided to try a different approach. Twelve community field workers of the hospital were initially given some training sessions, to teach them some basics of identifying mental illness in the community. These workers are recruited by the hospital from the local population and are used for a variety of community-based programs in a target area of seventy five villages within a radius of 30 km around Padhar. I started informal visits to some of the target villages once a week along with the respective field workers with the intention to screen patients for mental illnesses and refer them to the hospital. Surprisingly, without any intensive preparation or planning, we found 15 severely ill patients with a variety of diagnoses in the very first village we visited. Subsequent visits resulted in similar numbers. Gradually, the field workers began to screen their areas well in advance to facilitate my efforts.

Screening, however, was not the real problem. Very few of the referred patients actually ended up coming to Padhar, and the few that did, proved to be extremely difficult to follow up. Likely reasons included financial difficulties, lack of accessible public transport, unwillingness of relatives to leave a day’s work to bring patients, and lack of awareness of the effectiveness of treatment. In any case, it appeared that merely screening and referring patients was inadequate to make a difference in this community.

Since December 2014, rather than waiting for the patients to come to the hospital for treatment, we decided instead to take the interventions to the community setting itself. We focused our attention at first on the most severe cases (those with schizophrenia/other psychotic disorders, bipolar disorder, severe depression, epilepsy and mental retardation with treatable co-morbidities), and dispense medications to these patients in the field without payment. All patients and their relatives were educated about their conditions, the treatment strategies, and strategies to cope. Patients with less severe mental health issues (such as addictions, anxiety disorders, adjustment disorders, stress-related disorders etc) and especially those who needed more intensive non-pharmacological treatments like psychotherapy or family interventions were referred to the hospital (but had to pay for their treatment, though consultation and therapy charges could be reduced or waived on a case to case basis.). Where necessary, in very select cases, inpatient stay could be offered. Thus was born the Community Mental Health (CMH) project at Padhar Hospital.

We divided the seventy five target villages into eleven clusters based on geographical proximity, with one field worker in-charge and responsible for each cluster. Each cluster was centered around one or two large villages at central locations, to make planning and accessibility easier. Each Wednesday, a team including myself, the respective field workers, some nursing students (undergoing their psychiatry rotation) and an administrative coordinator visited one cluster of villages. Patients who are screened by the field workers prior to our visits are evaluated and appropriate intervention done, old patients are followed up. A few house visits are made for patients who are too sick or too far to come to the central location chosen. Since there are eleven clusters of villages, each cluster gets reviewed roughly every three months. In the intervening period, the respective field workers follow up patients in their area, and bring problems encountered to my notice so that they can be addressed as required.

To facilitate screening by the field workers, we have created a new screening questionnaire tool designed to be asked by non-professional workers verbatim to one member of each household to identify potential patients with mental illnesses and epilepsy. We are now simultaneously conducting an evaluation study of this tool to assess its sensitivity and specificity as a screening tool in rural Indian settings.

Every Saturday, all those involved hold a short meeting in which problems encountered are discussed and potential solutions considered. Plans for the next week, and specific issues involving individual patients are also discussed. These sessions also provide an opportunity to have brief workshop-style training for the field workers on specific issues that arise in the field such as managing problems in compliance and violent / suicidal patients in the field.

As of July 2015, 410 patients are registered under the CMH project and have been evaluated. Of these, 187 have received long-term medications in the field and are on follow up, and many others have been referred to the hospital for more intensive treatments (medication / psychotherapy.). The current break up of major diagnoses among those registered under the project is shown in the table below.

Schizophrenia & other psychotic disorders


Bipolar Disorder


Depressive disorders (Major Depression,

Dysthymia, Recurrent Depression etc)


Anxiety & other neurotic spectrum disorders


Alcohol use disorders


Mental Retardation


Autism/ Autistic spectrum disorders






Headache syndromes (including Migraines,

Tension headaches etc)


Other neurological disorders (including

stroke, Parkinson’s etc)


We have also started doing Group Therapy sessions in the field targeting patients with severe mental disorders / epilepsy and their family members once a month in one cluster (along with the outreach clinics). These will focus on issues such as nature of the disorders and their treatment, family burden, stigma and issues of social re-integration of these patients.

In terms of cost, the major expenses ultimately come down to medication and transport costs. Since the entire target area is within a radius of just 30 km, transport costs are minimal. We did not hire any new staff for the project – it is structured entirely with existing resources. We do consultations and Group therapy for free. By using cheap (but effective and trusted) brands of a select few drugs, we have managed to keep medication costs to just between Rs.100 – 200 per month for an average patient with severe mental disorder / epilepsy. This translates into just Rs.3/- to 6/- per day per patient, an incredibly small amount of money considering the tremendous impact the intervention has on the patient, family and community. At present we are running the project with a limited budget entirely based on donations by well-wishers. An effective Community Mental Health program is therefore an astonishingly cost-effective affair, unlike what is often portrayed.

One of the major challenges in any community-based mental health program will always be the re-integration of individuals who have been shunned by family and society for so long, and many of whom have, as part of their symptoms, lost their social and communication skills. In this respect, there are many similarities between leprosy work and work with the mentally ill; however there are some key factors in a rural mental health program such as ours that have played well to our advantage.

First, unlike patients with leprosy or cancer, patients with majority of mental illnesses (barring few congenital syndromes with developmental delays) do not look different from others around them. What stands out is their behaviour. And as behaviour improves, they become less conspicuous and easily merge into their community. A second advantage of rural areas is that the predominant occupations are agricultural work and manual labour, which do not demand a high technical knowledge and skill base. Finally, the strong cohesive joint family system which, despite some significant disadvantages, at least provides a solid support system to supervise and care for mentally ill patients at their homes until they get better (preventing the need for unnecessary hospitalization and labour and time of hospital staff).

Realizing these significant advantages, we have fortunately been quite successful in the community re-integration of several patients with severe mental illnesses and epilepsy in the target area. It is gratifying to see so many of our community patients who once behaved violently and roamed aimlessly through the villages or frequently fell unconscious with seizures now much better and back to work at home or in the fields. Once families understand that their symptoms can be controlled, and once they are encouraged to give them minor tasks at home or in the fields on a regular basis as the major symptoms improve, the patients easily begin to contribute economically and socially to their families and community. And in most instances, that itself diminishes the terrible isolation they have faced in silence for years.

Two stories (continued…)

Goddess in human form – The story of Priya.

     During one of the CMH outreach visits to the Chiklimal cluster of villages, Priya’s father brought her for evaluation. We evaluated her and recommended that admission in the hospital was necessary. During the two-week hospitalization (in which consultation and therapy charges were waived), the parents were educated about the nature of her condition and effective management strategies. She was started on Carbamazepine for her epilepsy, and on a low dose of Risperidone for her hyperactivity and stereotypical movements and speech. The patient and her parents also underwent intensive behaviour therapy, and techniques like activity scheduling, differential reinforcement and time-outs were employed using appropriate reinforcements.
     Over the course of her stay, her seizures were controlled, her hyperactivity and stereotypical movements decreased significantly. Her aggressive behaviour decreased considerably, meal times were regularized and she was able to remain without soiling her clothes throughout the day.
     Priya is one among many such patients with post-encephalitic syndromes we encounter frequently in our target villages. Several of these hapless patients develop their neuropsychiatric symptoms due to improper or delayed treatment (or in many cases non-treatment) of their initial encephalitic illness or seizures due to prevalent beliefs of supernatural causation of mental and neurological illnesses. This represents a group of preventable severe neuropsychiatric conditions, and we hope that through this project we may be able to improve awareness about the need for early and correct intervention in order to prevent or reduce the morbidity of these disabling disorders.

Demon possessed – The story of Dhanush
     During a field visit, one of the Project Coordinators (Mr. Achal) found that Dhanush was tied with an iron chain in one of the village temples for magico-religious exorcism rituals for demon possession. He was called to Padhar Hospital for psychiatric intervention a number of times but his family members refused to come. At this temple, his hands were branded with iron rods as part of the exorcism rites (he still bears the scars of these rituals on his palms). He remained in the same condition and was taken back to his home village.
    Subsequently, Dhanush was evaluated during one of our outreach visits under the Community Mental Health Project and was diagnosed to be suffering from Schizophrenia. He and his family were educated about the nature of his condition and the treatment required. He was prescribed Olanzapine for free for three months and reviewed at the subsequent review camp in his cluster. His family members started giving him medicines regularly and it transformed his behaviour. Now, he has stopped wandering around aimlessly and hitting people and remains at home. He also started supporting his family in household work as well as in the fields.


  1. WHO (2013) Mental Health Action Plan. World Health Organization, Geneva. Mental Health Program (2010)
  2. WHO (2011) Mental health atlas: country profiles on mental health resources. World Health Organisation, Geneva
  3. National Mental Health Program (2010)
  4. Census India 2011.
  5. Kumar A. Mental Health Services in India: challenges and prospects. Health. 2011;3:01 Vol. 3, No. 12, pp. 757-761

Brain abscess

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Brain abscess – Diagnosis and management

Tony Abraham Thomas, M. Ch (Neurosurgery), Ranjith K. Moorthy, M. Ch. (Neurosurgery)
Department of Neurosciences, Christian Medical College, Vellore

Brain abscess is relatively uncommon problem in general practice yet it is important to be aware of the problem and consider it as one of the differential diagnoses in an individual who presents with symptoms of raised intracranial pressure (especially if there are predisposing factors). Brain abscess is a potentially life-threatening illness and the treatment is almost always involves surgical intervention along with medical therapy. It is therefore essential to know when to suspect a brain abscess, when to refer and how to manage a patient before referral to a center with neurosurgical facilities.
Appropriate treatment results in a cure in more than 90% of cases.

Two case descriptions are given below. Try to answer the questions before you proceed to an overview on the diagnosis and management of brain abscess.

Case descriptions

  1. An eight year old girl was brought to the outpatient department with progressively worsening headache associated with vomiting for three weeks. She had recurrent cyanotic spells since the age of three years. On examination, her GCS score was 15/15 and she had left hemiparesis (grade 4 power in upper and lower limbs). There was central cyanosis. She had been treated elsewhere with multiple parenteral antibiotics for 2 weeks. A CT scan of the brain with contrast is shown in Fig. 1.
  2. A twenty five year old lady with systemic lupus erythematosus (SLE) who had been on oral steroids for three years complained of headache and vomiting for 2 weeks with episodes of blurred vision and one episode of generalized tonic-clonic seizure. MRI of brain with gadolinium was done (Fig. 2) and she was started on anti-tuberculous medications empirically elsewhere. Her symptoms continued to worsen.

Fig. 1: CT brain with contrast of case 1

Fig. 2: MRI brain with gadolinium of Case 2


What will you suspect as the cause of headache in each of these scenarios and why?
How would you approach this patient to arrive at a diagnosis and then to treat the illness?

See the end of the article for a brief discussion of these cases.

Definition and overview

Pyogenic brain abscess is a focal collection of pus in the brain parenchyma. It is a focal suppurative process which begins as a localized area of inflammation (cerebritis) within an area of devitalized brain tissue with poor microcirculation which then develops into a collection of pus with a well formed capsule.

In developing countries the incidence of brain abscess is about 8% of all intracranial tumours while it is lower in developed countries. 1 Improvement in living conditions and widespread use of antibiotics have not reduced the incidence because of the rise in the incidence of infection among immunocompromised individuals. Almost every person with a brain abscess died in the pre-antibiotic era6. The advent of antibiotics and CT imaging have ensured early diagnosis and reduced mortality rates significantly. Most patients in the present era are cured with medical and surgical therapy.

Pathogenesis of brain abscess

Brain abscess develops when microorganisms are introduced into brain parenchyma (1,2,11). The routes of entry of micro-organisms are as follows.

  1. Contiguous spread occurs in about 40% of abscesses, with spread from middle ear infection (acute or chronic suppurative otitis media), infection in paranasal sinuses (usually frontal and sphenoid) and mastoiditis. Middle ear infections are a common source and tend to result in abscesses in the temporal lobe and cerebellum. 2
  2. Haematogeneous spread occurs through the bloodstream from infectious focus at a distant site. Eg. Pulmonary infection (bronchiectasis, pneumonia, empyema), infective bacterial endocarditis, dental infection, osteomyelitis, acute diverticulitis. These metastatic abscesses are usually small and multiple. They are most common in the middle cerebral arterial territory. Spread of middle ear infection through septic thrombophlebitis of the sigmoid and transverse sinuses can also occur.
  3. Direct inoculation from outside – About 10% of abscesses are caused by spread of organisms introduced from outside (infected compound skull fracture, bullet injury, intracranial surgery).
  4. In about 10-37% of abscesses, the source of infection is not determined.

Children with congenital cyanotic heart disease and individuals who are immunocompromised due to HIV infection or long term corticosteroid therapy are particularly predisposed to developing brain abscess.

After inoculation of brain tissue, brain abscesses evolve from a stage of ill-defined cerebritis and oedema to gradual development of a capsule.

Micro-organisms that cause brain abscess

The organisms that cause brain abscess vary according to the predisposing condition (Table 1) and by age. The most common organisms that cause brain abscess are streptococci that are usually anaerobic or microaerophilic(1,3,10). In several cases there are multiple causative organisms. Mycobacterium tuberculosis or fungal infection can also result in brain abscess formation. Hence it is important to send pus for aerobic, anaerobic, fungal and acid-fast bacilli cultures.

Table 1: Common organisms according to predisposing conditions (3)

Predisposing condition

Likely pathogens

otitis media/mastoiditis

streptococci (anaerobic & aerobic), B. fragilis, Enterobacteriaceae spp

paranasal sinusitis

streptococci, Bacteroides spp, Enterobacteriaceae spp., S. aureus

dental infections

streptococci, Fusibacterium spp, Bacteroides spp


L. monocytogenes, C. diversus

cyanotic heart disease

streptococci, Haemophilus spp

bacterial endocarditis

S. viridans, Staphylococcus spp, enterococci, Haemophilus spp

pyogenic lung disease

streptococci, N. asteroides, Actinomyces spp, Bacteroides spp

T-cell deficiency

Toxoplasma gondii, Nocardia spp, L. monocytogenes


S. aureus, Enterobacteriaceae spp

Box 1,2,3

Clinical features

1. Features of raised intracranial pressure – Headache, vomiting, altered consciousness and visual disturbances (blurred vision, diplopia) are the commonest symptoms. Alteration in consciousness is seen in up to two-third of patients.

2. Seizures – is seen in up to 50% of cases

3. Focal neurological deficits – like weakness of the limbs, cerebellar dysfunction (impaired balance, gait ataxia), and other deficits are seen depending on the site and size of the abscess.

It should be noted that fever is not a common presenting symptom and if present, is usually low grade. Absence of fever should not exclude the suspicion of brain abscess.

Brain abscess is more common in the younger age group and for some reason, more common in males

Investigations and Diagnosis

If a patient with predisposing conditions like an ear infection or congenital cyanotic heart disease presents with features of raised intracranial pressure, the possibility of brain abscess must be considered and investigated.

Radiological imaging:

A computerized tomography (CT) with contrast administration is the quickest and cheapest investigation to confirm diagnosis and plan treatment. The abscess is usually seen as a ring-enhancing lesion with surrounding oedema. The enhancing rim is the capsule and this may be thin or absent in an early abscess.

MRI scans with gadolinium may be used when available. The advantage of MRI is that it can detect very small abscesses and the multiple planes of imaging aid in planning for surgery. In most cases however CT imaging is more than adequate.

Ultrasound imaging can be used to detect abscesses in children with an open anterior fontanelle.

If a brain abscess is diagnosed, further investigation to detect the source of the infection is important. The CT or MRI of the brain can detect sinusitis involving the paranasal sinuses, mastoidits, fractures of the skull. Further imaging of the abdomen and thorax may be necessary to look for infections in these regions. A consultation with an ENT surgeon is recommended to rule out an ear infection even if the imaging is negative.

Laboratory investigations

Lumbar puncture for CSF analysis is contraindicated as it can lead to life-threatening transtentorial herniation and transforaminal herniation of the brain. The process of herniation of the brain is slow (over several days) and may not manifest immediately after a lumbar puncture. Moreover, CSF analysis does not contribute to diagnosis since a brain abscess is a localized infection in the brain parenchyma unlike a meningitis and CSF analysis may be normal or inconclusive.

Routine blood investigations like Total WBC counts and ESR are usually normal or mildly elevated and do not contribute to diagnosis. Haemoglobin, serum creatinine, virology screening and crossmatch for transfusion may be sent if surgical intervention is planned.

Pus for culture: Pus from the abscess, once obtained must be sent immediately for aerobic, anaerobic and acid-fast bacilli (AFB) and fungal culture and sensitivity for a definitive diagnosis. Cultures must be sent immediately because delayed incubation can lead to false negative results and difficulty in antibiotic selection.

Differential diagnosis in CT/MRI:

The differential diagnoses in a patient with a ring enhancing lesion on imaging are high grade brain tumour and metastasis. Cystic lesions like solitary cysticercal granuloma are also ring enhancing lesions . The enhancing rim in a brain abscess is usually thinner and more uniform than in a brain tumour. Cysticercal lesions are usually small (less than 2 cms) and may be multiple and they usually present with seizures.

Treatment of brain abscess

The treatment of brain abscess is administration of parenteral administration of antibiotics after confirmation of the diagnosis by microscopic examination of pus (obtained by aspiration or surgical excision) and culture (1,2,3,5,6,7).

Aspiration of pus:

This may be done using a twist-drill / burr-hole and cannula or with sterotactic guidance. Aspirated pus has to be sent immediately for culture and sensitivity after which antibiotics are started as soon as possible. The pus has to be sent for aerobic, anaerobic, fungal and AFB (acid-fast bacilli) culture. Serial weekly CT scans may be done to monitor the size of the abscess. Repeated aspirations may be necessary . In case of multiple abscesses, the largest abscess must be aspirated, followed by antibiotics.


Antibiotics need to be given for 6-8 weeks and the choice of antibiotics is based on sensitivity of the organism. The antibiotics of choice are crystalline penicillin, chloramphenicol and metronidazole followed by antibiotics based on the sensitivity report. Third generation cephalosporins (ceftriaxone) may be used as an alternative to chloramphenicol.

At least 2 weeks of parenteral antibiotics followed by 4 – 6 weeks of oral antibiotics is recommended.

Empirical antibiotic therapy is not advisable because a definitive diagnosis of brain abscess either by aspiration of pus or excision and isolation of the micro-organism is essential to treatment.

The antibiotic schedule followed in CMC Vellore is as follows.

Until culture and sensitivity reports are obtained:

Inj. Crystalline Penicillin 50,000 units/Kg/dose every 2 hours IV (in children)

20 lakh units IV every 2 hours (adults above 60 Kg)


Inj. Chloramphenicol 100 mg/Kg/ day IV in four divided doses (in children)

1 gm IV every four hours ( adults over 60 Kg)

(in children – reduce the dose by half after 3 days)


Inj. Metronidazole 7.5 mg / Kg/ dose IV (every 8 hours)

Inj. Ceftriaxone (100mg/kg/day in children and 4 gm/ day in adults in two divided doses) may be used instead of chloramphenicol in case of availability issues or adverse drug reactions.

After culture and sensitivity report: Antibiotics may be altered according to the sensitivity pattern obtained.

After two weeks of intravenous antibiotics, oral antibiotics with good CSF penetration are recommended for 4 – 6 weeks depending on the causative organism. If no organism has been isolated, co-trimoxazole (double strength) may be given at the appropriate dose along with Rifampicin.

If staphylococcal infection is suspected, an anti-staphylococcal penicillin like cloxacillin may be used. Vancomycin is reserved for penicillin resistant Gram positive organisms and in case of penicillin hypersensitivity.

Anti-oedema measures:

Anti-oedema measures may be necessary in case of low level of consciousness due to raised intracranial pressure or if the scan shows significant cerebral oedema with mass effect. Mannitol is effective in lowering intracranial pressure.

Intravenous mannitol

Dose: 1-1.25 gm/kg/day in four divided doses for two days, taper dose to half on the third day. There is no benefit in continuing Mannitol beyond three days.

Corticosteroids for reducing oedema and intracranial pressure are not advisable in the presence of an infective process. A single dose of dexamethasone may be given as a life-saving measure before referring the patient. (See box 3)

Anticonvulsant medication

All patients with brain abscesses should be started on anticonvulsant drugs except for those with an abscess in the posterior fossa structures (cerebellum and brain-stem). An abscess in the cerebral parenchyma, especially within or close to the cortical grey matter is likely to cause seizure and an anticonvulsant drug with a broad spectrum of activity is recommended (Phenytoin, sodium Valproate or phenobarbitone). Phenytoin and sodium Valproate have the advantage of being available as intravenous preparations. Anticonvulsant drugs will have to be continued long term even after medical therapy and/or surgery. This is especially important in patients who have presented with seizures; these individuals will require anticonvulsant drugs for at least 3 years after treatment.

Surgical excision:

Surgical excision of the abscess (craniotomy and excision) is recommend in either of these cases

  1. the abscess is large with significant mass effect or multiloculated
  2. The abscess is superficial and not in an eloquent area of the brain
  3. Cerebellar abscess (they tend to cause rapid deterioration in clinical status especially if the abscess recurs after aspiration)

Surgical excision is not recommended if the abscess is deep-seated or is in an eloquent area of the brain or if the patient is clinically unfit for surgery. Aspiration of pus may be done in such cases with or without stereotactic guidance.

Role of stereotactic aspiration

Aspiration of pus and biopsy of the abscess wall may be done using stereotactic guidance in instances where the abscess is deep-seated or if the patient is unfit for surgery or if the abscess is in a region of the brain where surgery is not advisable because of the risk of severe neurological deficits (Eg. Thalamus, basal ganglia, brainstem abscesses). In stereotactic aspiration, the aspiration is done using a probe that is inserted using CT image guidance (usually under local anaesthesia). It is precise and effective in managing small, deep-seated abscesses with a very low risk to life and very little morbidity compared to surgery(8,9).

Treatment of the source of infection

Treatment of brain abscess is incomplete if the source of the infection has not been identified and treated. A meticulous attempt has to be made to ascertain the source of the infection and treat the infection. Middle ear and paranasal sinus infections and common predisposing conditions and can be detected using clinical examination and imaging (X-rays and CT). Ultrasound/ CT of the abdomen to look for intra-abdominal collections and echocardiogram to detect cardiac anomalies and valvular vegetations are recommended. A chest x-ray can detect bronchiectasis or large abscesses in the lungs. A source of infection however, may not be detected in some despite extensive investigation.

Congenital cyanotic heart disease

Congenital cyanotic heart disease (right to left shunt) is an important predisposing condition for development of brain abscess(1,2,3,11). It accounts for 12.8–69.4% of all cases of brain abscesses with identified risk factors in several series and the incidence of brain abscess in patients with cyanotic heart disease is between 5-18.7%. Tetralogy of Fallot is the commonest anomaly associated with brain abscess and most of the patients are children. In patients with cyanotic heart disease, there is a right-to left shunt of venous blood in the heart, bypassing the pulmonary circulation. Thus, bacteria in the bloodstream are not filtered through the pulmonary circulation, where they would normally be removed by phagocytosis. Patients with cyanotic heart disease could have low-perfusion areas in the brain due to chronic severe hypoxemia and metabolic acidosis as well as increased viscosity of blood due to secondary polycythemia. These low-perfusion areas commonly occur in the junction of gray and white matter, and they are prone to seeding by microorganisms that may be present in the bloodstream.

Individuals, especially children with cyanotic heard disease and a brain abscess may present only with headache and there should be a low threshold for performing a CT scan of the brain in this situation. Brain abscesses in these patients tend to be multiple. Since the cardio-pulmonary status in most patients is sub-optimal, general anaesthesia and surgical excision is usually contraindicated. These patients also have abnormal coagulation profile and are at high risk for open surgical procedure to excise the abscess. Repeated aspiration after correction of coagulation profile followed by antibiotics is the recommended treatment.

Fungal brain abscess:

Fungal infections may present as an abscess or granuloma in the brain although the rhinocerebral syndrome and meningitis are more common. Fungal infections are uncommon must be suspected if the patient is immunocompromised, though the infection may also seen in the immunocompetent. The commonest fungi that present a fungal mass in the brain are Phaeohypomycosis spp., Zygomycetes spp.,  Candida spp.,  and rarely with Aspergillus spp. Most of the fungi are inhaled and initiate a primary lung infection which is usually self-limited. The infection may then spread by hematogenous dissemination with subsequent involvement of the central nervous system (CNS). Local extension from paranasal sinuses, ear and orbit and rarely trauma are some of the other ways in which a fungal infection reaches the CNS. 4

Outcomes and long term sequelae

The majority of patients with brain abscesses in the present era are cured with medical and surgical treatment. The cure rate reported in literature is about 90% for single and multiple abscesses. Early diagnosis by CT scan and the availability of antibiotics have reduced mortality rates significantly. Some conditions associated with higher mortality and morbidity are

  1. Nocardial and listerial brain abscesses
  2. Intra-ventricular rupture of brain abscess and
  3. Low Glasgow Coma Scale score on presentation to hospital.

Cognitive dysfunction, delayed onset seizures and focal neurological deficits are some of the long term sequelae.

Discussion of case scenarios

Case 1
Brain abscess must be suspected in any patient with a background of cyanotic heart disease presenting with complaints of headache and vomiting. Imaging (CT or MRI) with contrast is the investigation of choice to arrive at a diagnosis. This patient was treated with aspiration of pus in multiple settings. Pus culture did not grow any organism since the child had been treated elsewhere with multiple antibiotics empirically. Definitive treatment in the form of aspiration or excision with pus smear and culture is a necessity in the treatment of brain abscess so that appropriate antibiotics can be administered. Empirical treatment with antibiotics without pus culture is usually ineffective and leads to diagnostic dilemmas.

Case 2

This lady had been on oral prednisolone for three years and in this setting, brain abscess should be suspected if there are symptoms of raised intracranial pressure or seizure. An empirical diagnosis of tuberculosis was made elsewhere and she was managed with ATT (anti-tuberculous therapy) without pus smear or culture and her symptoms worsened. The pus culture after CT guided stereotactic aspiration grew Nocardia and she improved with co-trimoxazole therapy. Nocardia and fungal species are uncommon causative organisms and emphasizes the need for sending all possible cultures in brain abscess (aerobic, anaerobic, fungal and AFB).


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