Effect of a multicomponent intervention on achievement and improvements in quality-of-care indices among people with Type 2 diabetes in South Asia: the CARRS trial.

AIMS: To evaluate whether and what combinations of diabetes quality metrics were achieved in a multicentre trial in South Asia evaluating a multicomponent quality improvement intervention that included non-physician care coordinators to promote adherence and clinical decision-support software to enhance physician practices, in comparision with usual care. METHODS: Using data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) trial, we evaluated the proportions of trial participants achieving specific and combinations of five diabetes care targets (HbA1c <53 mmol/mol [7%], blood pressure <130/80 mmHg, LDL cholesterol <2.6 mmol/L, non-smoking status, and aspirin use). Additionally, we examined the proportions of participants achieving the following risk factor improvements from baseline: ≥11-mmol/mol (1%) reduction in HbA1c , ≥10-mmHg reduction in systolic blood pressure, and/or ≥0.26-mmol/l reduction in LDL cholesterol. RESULTS: Baseline characteristics were similar in the intervention and usual care arms. Overall, 12.3%, 29.4%, 36.5%, 19.5% and 2.2% of participants in the intervention group and 16.2%, 38.3%, 31.6%, 11.3% and 0.8% of participants in the usual care group achieved any one, two, three, four or five targets, respectively. We noted sizeable improvements in HbA1c , blood pressure and cholesterol, and found that participants in the intervention group were twice as likely to achieve improvements in all three indices at 12 months that were sustained over 28 months of the study [relative risk 2.1 (95% CI 1.5,2.8) and 1.8 (95% CI 1.5,2.3), respectively]. CONCLUSIONS: The intervention was associated with significantly higher achievement of and greater improvements in composite diabetes quality care goals. However, among these higher-risk participants, very small proportions achieved the complete group of targets, which suggests that achievement of multiple quality-of-care goals is challenging and that other methods may be needed in closing care gaps.

Expert Group Consensus Opinion: Role of Anti-inflammatory Agents in the Management of Type-2 Diabetes (T2D).

Diabetes is a major public health emergency of the 21st century. Results of the Indian Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study have found prevalence of diabetes and prediabetes in India to be as high as 7.3% and 10.3%, respectively with nation-wide projection of 77.2 million people with prediabetes and 69.2 million with diabetes. It is well established that insulin resistance (IR) and islet ß-cell failure are the two major features of T2D Multiple mechanisms including glucotoxicity, lipotoxicity, oxidative stress, endoplasmic reticulum stress, formation of amyloid deposits in the islets, etc. have been hypothesized to participate in the pathology of the disease. In the concluding decade of the last century, numerous studies - prospective and cross-sectional, have confirmed the role of chronic low-grade inflammation as a pathogenetic factor of T2D. It has been shown that increased levels of various inflammatory markers and mediators including fundamental markers like white blood cell count, C-reactive protein (CRP) to the more specific circulating cytokines like, interleukin-6 (IL-6), IL-1ß, plasminogen activator inhibitor-1 (PAI-1), etc. correlate with incident T2D. Based on the robust evidence implying the role of inflammation in T2D pathogenesis, several studies have proven that the proinflammatory cytokines play a central role in the development of microvascular diabetic complications such as nephropathy, retinopathy, and neuropathy. Inflammation in T2D causes accelerated atherosclerosis which predisposes to CVD, the leading cause of mortality in these patients. Recently there is a considerable increase in the interest among the researchers about anti-inflammatory therapies in the setting of chronic disorders such as T2D and CV diseases. In a multi-country study conducted in Asia, approximately 50% of Indian respondents had poor diabetes control. Most patients initially respond to sulfonylurea and/or metformin, and later these agents lose their effectiveness with time. Therapeutic option in patients uncontrolled on two-drug combination therapy is either to add third oral drug or insulin. However, use of insulin is limited due to its high cost and poor compliance. Majority of new treatment options like GLP1 agonists, insulin analogs and SGLT2 inhibitors are costly considering they are still under patent. The thiazolidinedione class of drugs is associated with adverse effects like fluid retention and weight gain that may result in or exacerbate edema and congestive heart failure. Thus there is a need for a safe and inexpensive treatment option for the management of uncontrolled T2D. Considering the role of inflammation in T2D pathogenesis, the drug should not only have antihyperglycemic effects but also reduce inflammatory burden thus reducing the progression and complications of T2D. The current interest is apparently directed towards drugs targeting inflammation acting at different stages of the inflammatory cascade. In the recently published CANTOS study, canakinumab, a selective, high-affinity, fully human monoclonal antibody which inhibits IL-1ß, has no consistent long-term benefits on HbA1c. Other selective inhibitors like anakinra (IL-1 receptor antagonist) and etanercept (TNF inhibitor) too have yielded modest effects on glycemic parameters and insulin sensitivity. However, hydroxychloroquine (HCQ), a broad anti-inflammatory agent has been shown to reduce HbA1c by 0.87%. Hydroxychloroquine (HCQ) is considered as one of the safest disease modifying anti-rheumatic drug, used widely for the treatment of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The effect of HCQ in preventing development of diabetes in patients with chronic inflammatory diseases was highlighted in a prospective observational study of 4905 adults with rheumatoid arthritis and no diabetes with 21.5 years of follow-up. Patients who took HCQ for more than 4 years had a significant 77% lower risk of diabetes compared with non users of HCQ (RR, 0.23; 95% CI, 0.11-0.50). Taking cue from this study highlighting the anti-diabetic effect of HCQ, pioneering research studies evaluating these effects of HCQ were conducted in India. In 2014, hydroxychloroquine 400 mg got DCGI approval as an adjunct to diet and exercise to improve glycemic control of patients on metformin, sulfonylurea combination in Type 2 diabetes.

Consensus on Use of Insulins in Gestational Diabetes.

INTRODUCTION: Gestational Diabetes Mellitus (GDM), diabetes diagnosed during pregnancy is associated with maternal (caesarean delivery, hypoglycaemia, hyperbilirubinaemia, shoulder dystocia, pre-term delivery and birth trauma) and fetal (Hyperbilirubinaemia in offspring, Neonatal hypoglycaemia, Macrosomia) complications. Despite, insulin being the standard treatment for GDM cases, there is no existing comprehensive consensus update on use of insulin in Indian patients with GDM. OBJECTIVE: To provide simple and easily implementable guidelines to healthcare physicians on use of insulin in GDM. METHODS: Each consensus based on indications, choice of insulin regimen , titration and insulin therapy during intrapartum and postpartum was presented based on established guidelines and published scientific literature. These evaluations were then factored into the national context based on the expert committee representatives' patient-physician experience in their clinical practice and common therapeutic practices followed in India for successful GDM management. RESULTS: Recommendations based on use of insulin in GDM has been developed. The key recommendations are:to monitor fasting plasma glucose (FPG) and 2-hour post prandial glucose PPG levels and the glycaemic targets are: FPG < 95 mg/dL and 2-hour PPG < 120 mg/dL, short-and intermediate acting human insulin are the first choice of insulin regimens, rapid-acting (Insulin Aspart or Lispro) may be considered, use basal/intermediate acting insulin at bedtime, if FPG>110 mg/dL. During intrapartum, start IV insulin infusion with hourly glucose monitoring. Those women who require insulin < 20 U over 24 hours prior to labor may not need interpartum use of insulin infusion and Insulin dosing is stopped after birth and capillary glucose monitoring for 24-48 hours. CONCLUSIONS: We hope that the consensus based recommendations mentioned in this paper will be a useful reference tool for healthcare practitioners to achieve glycaemic targets in GDM patients.

Association of Physicians of India: Position Statement on Role of Chirally Pure Molecules in Clinical Practice.

Chirally pure molecules or enantiomers are non-superimposable mirror images of each other with a chiral center (such as carbon, sulphur, nitrogen or phosphorous atom). An equimolar mixture of enantiomers forms a racemate. Chirally pure molecules (single enantiomers) are important in the field of drug discovery as the drug targets such as enzymes and receptors are enantioselective in nature. Clinical studies have demonstrated that chirally pure drugs exhibit different pharmacokinetic and metabolic profiles, reduced adverse events, improved safety profiles and similar therapeutic activity at lowered drug dosage as compared with the racemate in many therapeutic areas. However, since there is a low level of awareness on the advantages of chirally pure molecules among clinicians, pharmacists and patients in India, the Association of Physicians of India (API) developed this position statement to increase awareness on the concept of chirality and the associated advantages of using chirally pure drugs in certain therapeutic areas to maximize patient outcomes. This includes the clinical evidence associated with single enantiomers such as S-metoprolol, S-amlodipine, esomeprazole, escitalopram, levobupivacaine, cisatracurium, S-etodolac, dexketoprofen, levofloxacin in terms of efficacy and safety as compared with their racemates. In addition, the API also provides some tactical recommendations for clinicians, pharmacists, patients, regulatory body and pharmaceutical companies to increase awareness on chirally pure drugs and puts forth the need for expedited availability of chirally pure drugs in the Indian market.

Regional and seasonal variations in ultraviolet B irradiation and vitamin D synthesis in India.

UNLABELLED: Evaluation of ultraviolet B index (UVBI) and its impact on vitamin D synthesis is important. We observed the maximum UVBI between 11 am and 1 pm. There was no increase in serum 25(OH)D levels following sun exposure during winter as the UVBI was significantly low, emphasizing the need for vitamin D supplementation during these months. INTRODUCTION: The amount of vitamin D3 synthesizing UVB irradiation (290-320 nm) reaching the earth's surface at different altitudes and seasons in different parts of India and it's impact on vitamin D synthesis has not been well studied. METHODS: The hourly UVB index (UVBI) from 10 am to 3 pm everyday for 12 months was measured by a solar meter in 4 different zones (North, Northeast, West and South) of the country. To study the impact of sun light exposure on vitamin D synthesis during winter, healthy school children aged 10-15 years were exposed to sunlight for a period of 30 min per day, between 11 am to 12 noon with 10 % body surface area, for 4 weeks. The main outcome measures were serum 25(OH)D, PTH, calcium, phosphate, and alkaline phosphatase levels before and after sun exposure. RESULTS: The mean UVBI was highest between 11 am and 1 pm throughout the year in all locations. The highest UVBI was recorded from the North zone (4.5 ± 2.7 µW/Cm(2)), while the least was recorded in the Northeast zone (2.1 ± 1.2 µW/Cm(2)). UVBI readings in the Northeast zone were consistently low throughout the year, while all the other three zones showed significant seasonal fluctuations. Surprisingly, we observed a significant decrease in serum 25(OH)D levels from baseline (6.3 ± 4.6 to 5.1 ± 2.7 ng/mL; p < 0.001) despite sun exposure. CONCLUSION: The mean UVBI was highest between 11 am and 1 pm throughout the year in all locations. No increase in the serum 25(OH)D levels was observed following sun exposure in winter, emphasizing the need for vitamin D supplementation during these months.

Translating structure to clinical properties of an ideal basal insulin.

There is a need for ideal basal insulin which can overcome the unmet need of a truly once daily insulin, with a flat peakless profile. Useful for all types of patients Insulin degludec is next generation insulin with a unique mode of protraction of forming soluble multi-hexamers and slow continuous absorption giving it a flat profile compared to the existing basal insulin. In patients with type 1 diabetes or with type 2 diabetes, at steady-state, the mean terminal half-life of insulin degludec was 25 hours, i.e., approximately twice as long as for insulin glargine (half-life of 12.1 hours). In once-daily dosing regimen it reaches steady state after approximately 3 days. The duration of action of insulin degludec was estimated to be beyond 42 hours in euglycaemic clamp studies and this gives the unique opportunity of flexible time dosing which is not an available option with the existing basal insulin. The glucose-lowering effect is evenly distributed across a 24-hour dosing interval with insulin degludec having 4 times lower variability than insulin glargine. This is an important attribute given the narrow therapeutic window of insulin and the goal of achieving night time and inter-prandial glycaemic control without increasing the risk for hypoglycaemia, a goal that is challenging given the variability of absorption and lower PK half-lives of current basal insulin products. The combination of the ultra-long, flat and stable profile with an improved hour-to-hour and day-to-day variability could present an improved risk-benefit trade-off with the lower risk of hypoglycaemia, allowing for targeting improved levels of glycaemic control.

Initiation of insulin aspart to Indian subjects on OADs show significant improvement in glycaemic outcomes: the A1chieve observational study.

The prevalence of diabetes is increasing worldwide and India stands second next only to china. The management of diabetes in real life settings needs to be evaluated for deriving better management practices. A1chieve observational study evaluated the use of modern insulin in real life settings. This was a 24-week, international, prospective, multicenter, non-interventional, observational study of people with type 2 diabetes. India recruited with 20,554 subjects and a total of 1815 patients were enrolled to receive insulin aspart as bolus insulin therapy of whom 1450 (79.9%) were insulin naïve and 365 (20.1%) were insulin users. At the end of 24 weeks, only one SAE was reported in this study and overall hypoglycemia events per patient year decreased from 2.49 (348 episodes) to 0.17 (20 episodes). There were no major hypoglycemic episodes reported in either insulin naive or insulin treated subjects. There was a significant improvement in the HbA(1c) values from the baseline in both insulin naive and insulin users. The mean HbA(1c) value was reduced from 9.5 to 7.4 (p < 0.001) for insulin naïve subjects and from 9.2 to 7.7 (p < 0.001) in insulin experienced subjects. Fasting plasma glucose values decreased by 70 mg/dL and 50 mg/dL in insulin naive and insulin experienced, respectively and the difference from baseline was statistically significant (P < 0.001). The post prandial glucose value was also significantly (p < 0.001) reduced by 105 mg/dL for insulin naïve subjects and 55 mg/dL for insulin experienced subjects. The composite end point was achieved by 46.6% of insulin naive and 38.1% of insulin-experienced subjects. The study concluded with good HbA(1c) reduction along with lower incidence of hypoglycemia and better health related quality of life outcomes in both in insulin naive and insulin experienced subjects who used insulin aspart as bolus insulin treatment.

Cardiovascular risk in newly diagnosed type 2 diabetes patients in India.

BACKGROUND: Type 2 diabetes mellitus (T2DM) worldwide continues to increase, in particular in India. Early T2DM diagnosis followed by appropriate management will result in more cardiovascular event free life years. However, knowledge of the cardiovascular profile of newly diagnosed T2DM patients is still limited. The aim of this study was to understand the extent of cardiovascular disease (CVD) risk of newly diagnosed T2DM patients in India. METHODS: A cross sectional observational study was conducted to evaluate clinical laboratory and socio-demographic parameters of 5,080 newly diagnosed T2DM patients (48.3 ± 12.8 years of age; 36.7% female). In addition, we determined their cardiovascular risk according to the guidelines of the Lipid Association of India (LAI) and the criteria of the QRISK3 score. RESULTS: Of the newly T2DM diagnosed patients in India 2,007(39.5%) were classified as "High risk" and 3,073 (60.5%) were classified as "Very high risk" based on LAI criteria. On average, patients had 1.7 ± 0.9 major atherosclerotic cardiovascular disease (ASCVD) risk factors. Low HDL-C value was the most frequent major risk (2,823; 55.6%) followed by high age (2,502; 49.3%), hypertension (2,141; 42.1%), smoking/tobacco use (1,078; 21.2%) and chronic kidney disease stage 3b or higher (568; 11.2%). In addition, 4,192 (82.5%) patients appeared to have at least one cholesterol abnormality and, if the latest LAI recommendations are applied, 96.5% (4,902) presented with lipid values above recommended targets. Based on the QRISK3 calculation Indian diabetes patients had an average CVD risk of 15.3 ± 12.3%, (12.2 ± 10.1 vs. 17.1 ± 13.5 [p<0.001] for females and males, respectively). CONCLUSIONS: Newly diagnosed Indian T2DM patients are at high ASCVD risk. Our data therefore support the notion that further extension of nationwide ASCVD risk identification programs and prevention strategies to reduce the occurrence of cardiovascular diseases are warranted.

Refractory rickets in the tropics.

Rickets is an important problem in children. The majority of rickets in children is due to deficiency of calcium, phosphorus or vitamin D. However, rickets may also be a feature of renal diseases, e.g. renal tubular acidosis, hypophosphatemic rickets or rickets associated with renal insufficiency. The treatment varies with etiology and hence complete workup is essential before initiating therapy.

Management of children and adolescents having type 1 diabetes during COVID-19 pandemic in India: challenges and solutions.

Purpose: Type 1 diabetes (T1D) requires a holistic approach and continuous care. The current COVID-19 pandemic has made the health care professionals realise its challenges even more ardently than in the normal times. In a country like India with its huge population burden and a significant number of people having T1D, the risk of COVID-19 in people having T1DM is considerably high. Methods: In this article, we are sharing our practical experiences of problems faced by children and adolescents having T1DM during the past 2 months of lockdown. Results: We have classified the challenges into 3 broad categories based on diabetes self-management, healthcare system and psychosocial aspects. We have tried to provide precise, comprehensive and region specific solutions to these challenges. Solutions briefly include maintaining the supply chain of essentials like insulin, syringes and glucose meter strips to psychological support, financial aid and support for hospitalization in case of COVID-19 itself or diabetes complications including diabetic ketoacidosis. Conclusions: Children and adolescents having T1DM require special care and attention during this period of COVID-19 pandemic because of various challenges as discussed. Our proposed solutions may help them overcome these problems and help them in better diabetes management during such emergency situations.

Effect of Gliclazide or Gliclazide plus Metformin Combination on Glycemic Control in Patients with T2DM in India: A Real-World, Retrospective, Longitudinal, Observational Study from Electronic Medical Records.

BACKGROUND: The efficacy of gliclazide has been reported in clinical trials in India. However, real-world data on the effectiveness of gliclazide in India is unavailable. OBJECTIVE: To provide real-world evidence regarding the effectiveness of gliclazide or gliclazide + metformin fixed-dose combination or separate medications, used either as monotherapy or as the latest add-on to other antihyperglycemic agents in reducing glycated hemoglobin (HbA1c) levels in Indian patients with type 2 diabetes mellitus (T2DM). METHODS: Electronic medical record data of adult patients who were diagnosed with T2DM who were newly initiated on or had been prescribed gliclazide or gliclazide + metformin combination for < 30 days as monotherapy or as add-on therapy to other antihyperglycemic agents, and had HbA1c ≥ 6.5% were retrospectively analyzed. Mean change in HbA1c from baseline was the primary endpoint. Secondary endpoints were assessment of dosages and formulations of gliclazide or gliclazide + metformin prescribed in the HbA1c spectrum and antihyperglycemic agents to which gliclazide or gliclazide + metformin was added as an adjunct. Readings were obtained before initiating gliclazide or gliclazide + metformin and after at least 90 days of treatment with gliclazide or gliclazide + metformin. RESULTS: Included patients (n = 498) were categorized into gliclazide only (n = 66), gliclazide + metformin only (n = 179), gliclazide add-on (n = 169), and gliclazide + metformin add-on (n = 84) groups. Mean (95% confidence interval [CI]) change in HbA1c among patients with baseline HbA1c > 7% was - 0.8% (- 1.26, - 0.34) in gliclazide only group; - 1.6% (- 1.89, - 1.31; p < 0.001) in gliclazide + metformin group; - 1.2% (- 1.50, - 0.90; p < 0.001) in add-on gliclazide group; and - 1.4% (- 1.75, - 1.05; p < 0.001) in add-on gliclazide + metformin group. Gliclazide once daily was the most prescribed regimen in the gliclazide only group (72.7%), with 60 mg being the most prescribed modified-release dose (62.5%). Gliclazide + metformin twice daily was the most prescribed regimen in the gliclazide + metformin group (69.3%) with 80 mg + 500 mg being the most prescribed immediate-release dose (62.9%). Gliclazide and gliclazide + metformin were most added as an adjunct to existing prescriptions of biguanides (83.4%) or insulin (64.3%), respectively. CONCLUSION: Gliclazide or gliclazide + metformin prescribed as mono- or add-on therapy during routine clinical practice effectively reduced HbA1c in Indian patients with T2DM, thus validating the use of gliclazide and gliclazide + metformin for managing T2DM in India.

"Worm in the eye": the rationale for treatment of DUSN in south India.

AIM: To discuss the rationale for different techniques of treatment for DUSN (diffuse unilateral subacute neuroretinitis) and their effectiveness in two patients from south India. METHODS: Two rare cases of live worms in DUSN from India are reported, where filarial Brugia malayi is endemic. Both cases presented with progressive unilateral loss of vision with no history of animal contact. They were 40 year old, apparently healthy men. In case 1, the worm (1500-2000 microm) was easy to identify with wriggling movements among crisscrossing diffuse subretinal tracks. The worm was destroyed by a single shot of laser to its advancing end, which was followed by oral steroid to control the inflammation caused by the dead worm. In case 2, the worm was small and difficult to identify. Initially diffuse neuroretinitis was diagnosed and treated with intravenous methylprednisolone and oral corticosteroid. A week later, a small live worm (400-600 microm) was found and subsequently destroyed by laser photocoagulation followed by a combination of anthelminthics. RESULTS: The patients' vision had improved to 6/60-6/36 from counting fingers after a few weeks. CONCLUSION: The role of a combination of laser treatment, systemic steroid, and anthelminthics is discussed.

Hepatitis in falciparum malaria.

BACKGROUND: Hepatocellular jaundice occurring in patients with falciparum malaria has been called as malarial hepatitis. METHODS: We studied 95 consecutive patients admitted with falciparum malaria. Of these 20 had evidence of malarial hepatitis. Their clinical presentation, complications and response to treatment was compared with that of patients without evidence of malarial hepatitis. RESULTS: The clinical presentation of these patients was not different from those without hepatitis. However, the incidence of complications such as renal failure (60% vs 25%; X2 = 8.47, p < 0.01), Adult Respiratory Distress Syndrome (35% vs 3%; X2 = 18.13, p < 0.001) and septicemia (20% vs 6%; X2 = 4.01, p < 0.05) was significantly higher. The mortality also was higher in the group of patients with malarial hepatitis (40% vs 17%; X2 = 4.85, p < 0.05). CONCLUSIONS: We conclude that the presence of hepatitis in patients with falciparum malaria indicates a more severe illness with a higher incidence of complications and a poor prognosis.

Neurological emergencies--diabetes management.

Diabetes can affect the nervous system in several ways. Of all the neurological complications of diabetes, peripheral neuropathy is by far the commonest and has been extensively studied. The involvement of central nervous system can be in several forms. The underlying damage may be due to involvement of the large and small cerebral blood vessels as also due to metabolic derangement caused by prolonged hypoglycemia, anoxia or ketoacidosis. The neurological emergencies that occur in diabetes can be: 1) atherothrombotic and lacunar strokes; 2) convulsive disorder in the setting of both hypo and hyperglycemia; 3) coma; 4) cranial neuropathies; and 5) acute proximal muscle weakness. In patients with diabetes, atherothrombotic stroke is associated with poor outcome. Hyperglycemia at the time of stroke is an important risk factor for an adverse outcome than chronic stable diabetic state. Proper management of diabetes in these acute situations is crucial for a better outcome of the underlying disease process.

Frequency, clinical features and risk factors of lacunar infarction (data from a stroke registry in South India).

Analysis of 893 patients of ischaemic stroke in the stroke registry of Nizam's institute of Medical Sciences, Hyderabad is presented. 16% of them had lacunar infarction. The mean age at presentation was 56.9 years and male to female ratio was 3.5:1. The common risk factors included hypertension(62%),diabetes(38%) and smoking(28%). Six percent had an underlying cardiac source of embolism and none had significant (>50%) extracranial carotid atherosclerosis. In 22% of patients, no obvious risk factors could be identified. The frequency of risk factors was similar in patients with lacunar and non- lacunar infarctions. However, patients with lacunar infarction had higher frequency of diabetes and absence of significant (>50%) extracranial carotid artery disease. Pure motor hemiparesis was the presenting syndrome in 45% patients. Ataxic hemiparesis and sensorimotor stroke accounted for 18% each and dysarthria-clumsy hand syndrome for 14%. This study suggests that the frequency, risk factors and clinical profile of lacunar infarction in our stroke registry is similar to most of the western stroke registries.

Cerebral salt wasting syndrome in a patient with a pituitary adenoma.

Cerebral salt wasting syndrome (CSWS) is often an unrecognized cause of hyponatremia that occurs in the setting of intracranial lesions. It is important to differentiate CSWS from the syndrome of inappropriate ADH secretion, as this would alter the management of hyponatremia. We describe a case of CSWS that occurred in association with a non-functioning pituitary adenoma.

Snake bite presenting as acute myocardial infarction, ischaemic cerebrovascular accident, acute renal failure and disseminated intravascular coagulopathy.

An unusual presentation of a viperine snake bite presenting with ischaemic damage to the major organs like brain and heart leading to cerebrovascular accident and acute myocardial infarction along with acute renal failure and disseminated intravascular coagulopathy (DIC) is described in this report.

Malignancy in rheumatoid arthritis--a report of two cases.

The development of malignancy in the setting of pre-existing connective tissue disease is well known. We report two cases of rheumatoid arthritis who developed malignancy--multiple myeloma in one of them and carcinoma cervix in the other. Case 1 was a 62 year old man, who developed multiple myeloma three years after the onset of rheumatoid arthritis. Case 2 was a 61 year old female with history of rheumatoid arthritis for two years and who developed carcinoma cervix.