INTERPRETATION AND ESTIMATION OF CONDITIONAL POWER IN INTERIM ANALYSES OF CLINICAL TRIALS: OFTEN IGNORED IN DECISION MAKING PROCESS

In group sequential trials, the interim results are more promising in the early termination of a trial either for efficacy or futility of the trial. This reduces the cost and time implications. Moreover, interim analyses play a key role to tackle the problem that arises due to adverse effects. In concern with the early stopping of trials, there are numerous stopping methods among them the Conditional power (CP) approach is best recommended. The CP approach provides the probability of getting significant results at the end of the study given the data observed so far. There are very few Indian studies that had incorporated the concept of CP and made decisions based on the results. This study popularises the CP approach detailing computing and its interpretation and is thereby facilitating clinical researchers to use this approach effectively. We have used real-time and hypothetical examples and illustrated the concept of CP under trend, CP under null, and CP under design. We suggest stopping the study for efficacy when the CP under null is greater than 80% and stopping the study for futility when CP under trend is less than 30%.

Changes in olfaction & quality of life following standard medical therapy in patients with intermittent & persistent allergic rhinitis

Background & objectives: Allergic rhinitis (AR) is an inflammatory disease prevalent worldwide which can affect both olfaction and quality of life (QoL). The objective of the present study was to assess olfaction and QoL changes in patients with AR before and after medical therapy. Methods: Adult participants (>18 yr) with AR were recruited for this study. These patients prospectively underwent olfaction testing using the modified Connecticut Chemosensory Clinical Research Centre Test and QoL assessment using Rhinoconjunctivitis QoL Questionnaire (RQLQ) before and after standard medical therapy with topical steroids and/antihistaminics. Results: Of the 150 patients recruited, 72 per cent had intermittent AR. The symptom of hyposmia was present in 34 patients (22.7%) and was more prevalent in patients with moderate-to-severe type of AR (P<0.001). However, olfaction testing revealed hyposmia/anosmia in 44 patients (29.3%). Mean composite olfaction scores were significantly higher in patients with mild AR compared to moderate/ severe AR (P=0.026). The pre-therapy mean composite olfaction score in the 34 patients with olfaction disturbances was 3.1 standard deviation (±1.06 SD). Following therapy, the mean composite olfaction score rose to 4.3 (±1.34 SD) and this change was found to be significant (P<0.001). Mean pre-therapy RQLQ scores were 2.87 (0.06-5.33) overall. Significant improvement was also found in RQLQ scores following therapy (P<0.001). Mean RQLQ scores were significantly lower in those with moderate-to- severe AR (P<0.001) as well as those with intermittent AR (P=0.004). Nine patients had persistently high RQLQ scores after medical therapy. Interpretation & conclusions: Both olfaction and QoL showed significant improvement after medical therapy in Indian adults with AR. In those patients who do not improve, other causes must be sought for the persistent symptoms.

Characteristics of treatment-naïve HBV-infected individuals with HIV-1 coinfection: A cross-sectional study from South India

Purpose: Human immunodeficiency virus-1 (HIV-1) and hepatitis B virus (HBV) coinfection has become a major health problem across the globe. The increased life expectancy of HIV-1 patients due to antiretroviral therapy has led to the emergence of liver disease as a major mortality factor among them. The purpose of the study was to examine the baseline characteristics of HBV in treatment-naïve HBV/HIV coinfection from southern India compared to monoinfected individuals. Materials and Methods: The study was cross sectional in design, and samples were examined from 80 HIV-1, 70 HBV and 35 HBV/HIV-coinfected individuals using chemiluminescent microparticle immunoassay, real-time polymerase chain reaction and flow cytometry assays. Results: There was a significant increase in HBV DNA (P = 0.0001), higher hepatitis B e antigen percentage difference (P = 0.027) and lower CD4 counts (P = 0.01) among the HBV/HIV-coinfected individuals, but no difference in the HIV-1 viral load compared to HIV-1-monoinfected individuals. Also, the aspartate aminotransferase levels, prothrombin time and the international normalised ratio were significantly high among coinfected individuals. Conclusion: These findings conclude that HIV-1 coinfection can have serious implications on the outcome of HBV-related liver disease. To the contrary, HBV infection had no consequence on the progression of HIV-1 disease but distinctly lowered CD4+ T-cells.

Usefulness of ultrasound-guided measurement of minimal transverse diameter of subglottic airway in determining the endotracheal tube size in children with congenital heart disease: A prospective observational study

Introduction: The search for an accurate and predictable method to estimate the endotracheal tube (ETT) size in pediatric population had led to derivation of many formulae. Of this, age-based formulae are the most commonly used. Studies have shown that minimal transverse diameter of subglottic airway (MTDSA) measurements using a high-frequency probe improves the success rate of predicting the airway diameter to about 90%. We did a prospective observational study using MTDSA as the criteria to select the size of ETT in children with congenital heart disease. Methods: In this prospective observational study, 51 children aged from 1 day to 5 years, scheduled for cardiac surgery, were enrolled for this study. The ETT size was guided solely based on the MTDSA. Leak test was used to determine the best-fit ETT size. Results: Data from 49 patients were analyzed. Agreement between the ETT determined by MTDSA and that predicted by Cole's age-based formulas with the best-fit ETT size was analyzed using a Bland–Altman plot. Conclusion: Age-based formula showed poor correlation (27.5%) compared to MTDSA (87.8%) in predicting the best-fit ETT. We observed that pediatric patients with congenital heart disease need a larger sized ETT as compared to what was predicted by age-based formula. Using ultrasound MTDSA measurements to guide selection of ETT size is a safe and accurate method in pediatric cardiac population.

Post-HAART tuberculosis in adult patients with HIV in India; Incidence, Clinical and Immunological profile.

Bacground: Highly Active Antiretroviral Therapy (HAART) was introduced in National AIDS Control Programme in 2004 to reduce the morbidity and mortality among those affected with HIV/AIDS. Tuberculosis, being an important coinfection, its emergence / occurrence in post-HAART period has potential implications. Objective:: Primary objectives were to study the incidence of post- HAART tuberculosis in HIV patients and to identify the possible risk factors. It was also intended to understand the clinical and immunological profile of this important condition. Methodology: Eligible adults and adolescents with HIV disease enrolled on HAART at Government Hospital of Thoracic Medicine, Tambaram Sanatorium, Chennai, from April, 2004 to March, 2007, formed the study population. They were monitored and screened for the occurrence of tuberculosis after commencing HAART. Clinical details and immunological profile of these patients were analysed. Results: Two hundred and sixty-two patients (5.1%) of 5099 patients followed-up for one to four years were found to have Post HAART TB with 100-person year risk of 2.83. Post HAART TB occurred predominantly in men (67.6%) and in 31- 44 years age group (69.8%) with 100-person year risk being 3.26 and 2.83 respectively. Pulmonary, Extra-pulmonary and disseminated tuberculosis were found to occur in the frequencies of 78%, 16% and 6% respectively. A total of 144 patients (54.9%) developed tuberculosis within six months and this number increased to 202 (77%) by 12 months. 230 patients (87.7%) had base level CD4 cell count < 200 / mm3. Conclusion: Tuberculosis was found to occur pre-dominantly in adult male patients with HIV during the first year after the initiation of HAART. Significantly, occurrence of Post HAART TB remained almost the same (5%) among patients treated for TB prior to the initiation of HAART.

Demographic & clinical profile of HIV infected children accessing care at Tambaram, Chennai, India.

BACKGROUND & OBJECTIVE: Human immunodeficiency virus (HIV) is severely affecting the poorly educated and economically disadvantaged in Indian society. When children start developing clinical manifestations, needing treatment, they have to travel long distances for accessing care and support at tertiary institutions. This places an extra burden on patients, who are already struggling to cope with their illness. Sufficient data are needed for the government to evolve appropriate policy for providing care to the children affected with HIV. We undertook this study to present the socio-demographic characteristics, signs and symptoms, clinical profile, distance travelled and follow up pattern of HIV positive children who accessed care for the first time in a referral hospital at Chennai, India. METHODS: Electronic medical records from patients diagnosed with HIV between 2002 and 2004 at the Government Hospital for Thoracic Medicine (GHTM) in Tambaram (Chennai) in India were analyzed to understand care-seeking behaviours. Demographic variables such as age, sex, education and occupation, data on clinical manifestations were examined together with geographic information. RESULTS: At GHTM 1,768 new paediatric patients accessed care from 2002 to 2004. Children aged less than 5 yr were 49.9 per cent; 1115 children had (63%) tuberculosis. Significantly, 14.9 and 20.6 per cent children had extra-pulmonary TB and disseminated TB respectively. Lower respiratory infection (15.8%), Pneumocystis carinii pneumonia (15.20%), oral/oesophageal candidiasis (13.5%), wasting (6.1%) and diarrhoeal disorders (3.5%) were the common clinical manifestations. In all 47 per cent children traveled between 200-400 km from home and 14 per cent travelled over 400 km. INTERPRETATION & CONCLUSION: Our findings showed that tuberculosis should be regarded as the indicator disease for HIV infection in children, especially when they have clinical manifestations of progressive, non pulmonary and disseminated disease. The primary and secondary health care centres should have the trained capacity to diagnose and treat HIV disease and opportunistic infections so as the children to have much needed care and support nearer to their residence.

Antimicrobial prescription patterns for common acute infections in some rural & urban health facilities of India.

BACKGROUND & OBJECTIVES: Irrational use of antimicrobials is a key factor behind rapidly spreading antimicrobial resistance in microorganisms. This study was undertaken to determine the rate and pattern of antimicrobial prescribing in patients with uncomplicated acute respiratory infections, fever and diarrhoea attending a few rural and urban health settings. METHODS: The study was done in primary and secondary health care facilities of public/government and private settings at four sites in India. Patients with fever, cough, diarrhoea or ear, nose or throat infections of < 7 days were included. Pregnant women, lactating mothers, infants, seriously ill patients and patients with bloody diarrhoea or purulent nasal or ear discharge were excluded. RESULTS: Overall antimicrobial prescription rate was 69.4 per cent (95% CI 67.1, 71.7). Wide variation was observed (Thiruvananthapuram 47.6%, Lucknow 81.8%, Chennai 73.1% and Vellore 76.5%). Physicians practicing in rural and public/government settings prescribed antimicrobials more frequently than those in urban and private settings (83.8, 81.9, 68.3 and 68.2% respectively). Antimicrobials were more frequently prescribed for patients presenting with fever. Highest rate was noticed for children aged between 6 and 18 yr. Patients of the high-income group received antimicrobials more frequently (72.7%). In both public/ government and private settings, for patients who purchased medicines, the rate was higher (82.4 and 68.9% respectively), vs. those receiving free medicines (70.2 and 46.2% respectively). Two third of all antimicrobials prescribed were penicillins and co-trimoxazole, and > 40 per cent of prescriptions from private sector were quinolones and cephalosporins. INTERPRETATION & CONCLUSIONS: Our findings showed that prescription of antimicrobials for acute respiratory infections and diarrhoea was extremely common and warrants interventional strategies.

Effectiveness of Management of HIV-TB Patients Under Programme Conditions in India.

HIV patients, on antiretroviral therapy (ART), with co-existing tuberculosis patients were assesed for clinical and immunological progress at GHTM ART centre for effectiveness of management programme. Six hundred and twenty two HIV-TB patients are placed under both Anti-TB Treatment (DOTS) and ART. While 337 patients are continuing their ATT, details of the remaining 283 patients are provided. 214 patients (76%) completed their treatment successfully. 29 patients (10%) expired before completing treatment for TB and 40 patients (14%) were treatment defaulters. Immunologicallly CD4 cells registered significant increase from 101(mean) to 306 (mean) in 202 treatment-completed patients (p=.001). Linking HIV patients on ART to their nearest DOTS centres for treating tuberculosis is feasible. High Mortality, even before completing the prescribed course of ATT is attributable to low immunity and complicating opportunistic infections. Referral and linkage services shall be improved and strengthened for enhanced treatment adherence.

Biochemical and clinical profile after organophosphorus poisoning--a placebo-controlled trial using pralidoxime.

BACKGROUND: Organophosphorus (OP) compounds are the most common suicidal poison in developing countries and mortality continues to be high. METHODS: A study was done to see butyryl cholinesterase (BuChE) profile after OP poisoning in pralidoxime (P2AM) and placebo treated cases. Highest recommended dose of P2AM was used to study the reactivation of cholinesterase. Clinical outcomes like, correlation of BuChE and severity of poisoning, mortality and complications like Type I and II paralysis, need for ventilation and ICU stay were also studied. RESULTS: Twenty one cases of moderate and severe poisoning with OP compounds were included in the study. Mean BuChE levels came up gradually over 6-7 days, some taking up to two weeks. There was no. difference between the treatment and placebo groups. BuChE levels did not correlate with severity of poisoning nor did it correlate with Type I or II paralysis, need for ventilation, ICU stay or mortality. CONCLUSIONS: Treatment with P2AM does not make any difference in BuChE reactivation or complications of moderate and severe OP poisoning. We have not been using P2AM for OP poisoning in our medical ICU with good patient outcomes.

Community prevalence of hepatitis B infection and modes of transmission in Tamil Nadu, India.

BACKGROUND AND OBJECTIVE: There have been very few community based studies on prevalence of hepatitis B virus (HBV) infection in India. We undertook this study to determine the prevalence of HBV infection in a southern State of India, Tamil Nadu and to describe the important factors related to transmission of the virus in the community. METHODS: Analysis of stored blood samples from a representative population of Tamil Nadu from an earlier community cluster survey on sexually transmitted diseases (STD) prevalence using proportionate to population size (PPS) technique was done. Serum markers of HBV viz., hapatitis B surface antigen (HBsAg), hepatitis B e antigen (HBe Ag) and antibody to surface antigen (anti-HBs) were performed. RESULTS: 1981 subjects were screened in the study. HBsAg prevalence was 5.7 per cent (CI 4.6- 6.8) with 23.5 per cent (25/106) of these having positive HBe-antigen. Community seroprevalence (HbsAg + anti-HBs) of hepatitis B infection was 27.4 per cent (CI: 25.3-29.5) with the highest prevalence of 32.7 per cent (CI: 30.2-35.2) noted in the 15-20 yr age group. Significant independent association (OR 1.4; P=0.006) was detected with family history of exposure to HBV infection by logistic modeling. Other risk factors noted to have significant association were use of disposable needles during injection (OR 0.5; P=0.02) in men, smoking (OR 3; P=0.04) and use of condom (OR 0.6; P=0.08) in women. INTERPRETATION AND CONCLUSION: This community based study shows a high prevalence of hepatitis B infection in the state of Tamil Nadu with the highest prevalence being in the younger (15-20 yr) age group. High prevalence rate in childhood with e-antigenemia seen in 23.5 per cent of HBsAg positive subjects suggest childhood transmission. Poor injection practices and high-risk sexual behavior were found to be additional risk factors for transmission of the disease in the community.

Effect of potassium channel modulators on toxicity of Cleistanthus collinus.

The study was conducted to determine the effects of boiled extract of Cleistanthus collinus on rats by observing ECG changes and electrolyte levels in serum and urine. Influence of minoxidil and glibenclamide on Cleistanthus collinus induced toxicity was determined. ED50 for arrhythmia, changes in contractility and heart rate were recorded using the isolated frog heart. Cleistanthus at low doses caused transient tachycardia and increase in contractility and at high dose caused arrhythmia and cardiac arrest in rat. LD50 was found to be 1690 mg/kg. Minoxidil potentiated cardiac toxicity, whereas glibenclamide did not produce any significant change. High concentration of potassium in Cleistanthus extract hindered comparison of its levels. There was excretion of sodium even in the presence of hyponatraemia. Cleistanthus at low dose caused transient tachycardia and increase in contractility and at high dose caused arrhythmia and cardiac arrest in isolated frog heart. ED50 for arrhythmia was found to be 1406 mg/kg. Acute toxicity was mainly due to depressive cardiac activity of Cleistanthus. It also caused renal failure. Potassium channel modulators did not have important role in acute cardiac toxicity treatment. Probably in chronic toxicity, electrolyte level changes are involved and potassium channel modulators might have a role.

Serodiagnosis of syphilis in a community: An evaluatory study.

PURPOSE: To analyse the prevalence of syphilis in the apparently healthy population and to provide data for implementation of the joint STD/HIV control programme, a population based study was undertaken by using 'probability proportional to size' cluster survey method in three randomly chosen districts of Tamil Nadu, India namely Dindigul, Ramnad and Tanjore. METHODS: Blood samples were collected from adults (n=1873) aged 15-45 years, from the selected households enrolled in this study. The sera were tested parallelly by rapid plasma reagin (RPR) and Treponema pallidum haemagglutination (TPHA) tests. Reactive samples by RPR and/or TPHA were later analysed by fluorescent treponemal antibody absorption (FTA-ABS) test. RESULTS: The prevalence of syphilis in the community of Tamil Nadu as per RPR positivity was 2.7% (50/1873) as against 0.7% by TPHA (13/1873). FTA-ABS positivity was observed in only 12 out of 48 (25%) RPR/TPHA reactive samples tested. By taking the positivity by two of the three tests, the community prevalence of acute ongoing syphilis in Tamil Nadu was determined as 1.1% (20/1873). CONCLUSIONS: The results confirmed that no single serological test for syphilis can act as the marker of ongoing acute infection in an apparently healthy population. The study suggests that for specific diagnosis of ongoing syphilis, the FTA-ABS test may be performed along with RPR and TPHA.

Oxidative damage in intermediate syndrome of acute organophosphorous poisoning.

BACKGROUND & OBJECTIVES: The main cause of morbidity due to organophosphate poisoning is intermediate syndrome (Type II paralysis) that can occur 48-72 h after poisoning. Mechanisms that underlie the intermediate syndrome are not known. This study investigates the role of oxidative damage to muscles as a possible mechanism underlying the development of the intermediate syndrome. METHODS: Nineteen patients with acute organophosphate poisoning were evaluated from admission to discharge from intensive care for the severity of poisoning and the development and duration of the intermediate syndrome. Blood cholinesterases and parameters of oxidative stress were studied daily and their temporal profiles analysed according to the severity of poisoning and the development and duration of the intermediate syndrome. RESULTS: Fifteen patients had severe poisoning and 16 developed intermediate syndrome. There was a positive association between the severity of poisoning and the occurrence of intermediate syndrome. There was no association between the organophosphate ingested and the development of intermediate syndrome. Erythrocyte membrane acetylcholinesterase and serum butyrylcholinesterase levels at admission and over the course of poisoning were significantly (P < 0.001) reduced in patients compared to controls. There were significantly (P < 0.05) higher levels of lipid peroxidation, conjugated dienes and protein thiols in erythrocyte membranes of patients who developed the intermediate syndrome compared to healthy controls, in patients who developed intermediate syndrome compared to those who did not and in patients with long compared to short duration intermediate syndrome. INTERPRETATION & CONCLUSION: In acute organophosphate poisoning, severe and prolonged acetylcholinesterase inhibition is associated with oxidative stress, detected in erythrocyte membranes, that occurs early in the course of poisoning and may contribute to the development and severity of intermediate syndrome.

Community prevalence of sexually transmitted diseases and human immunodeficiency virus infection in Tamil Nadu, India: a probability proportional to size cluster survey.

BACKGROUND: Human immunodeficiency virus (HIV) infection and AIDS is threatening the survival of many nations. To evaluate ongoing interventional strategies and burden of illness estimates, valid data on the prevalence of HIV are required. Often, in the absence of community prevalence data, estimates are based on surrogate markers such as prevalence of HIV in antenatal clinics. Even though the antenatal prevalence of HIV is easier to measure and can be repeated for evaluation, it is important to establish the association between antenatal and community prevalence of sexually transmitted diseases (STDs) and HIV, so that the validity of the estimates can be verified. METHODS: A 'probability proportional to size' cluster survey was conducted in three randomly selected districts of Tamil Nadu in India. The basic unit of the survey was households from rural and urban clusters. Adults 15-45 years of age from the selected households were eligible for recruitment. Demographic, behavioural and laboratory data were collected. Clinical examination was done to identify STD syndromes and blood, urine, vaginal/urethral and endocervical swabs were taken for laboratory diagnosis of STDs from the subjects. Direct smear examination for Trichomonas vaginalis; serological tests for syphilis, hepatitis B, HIV, herpes simplex virus 2, Chlamydia trachomatis; and culture of Neisseria gonorrhoeae and Haemophilus ducreyi were performed on the collected specimens. The data were analysed adjusting for cluster effect. RESULT: We selected and screened 1981 individuals (1157 women and 824 men) for STDs and HIV from 1114 households representing the 25 million projected adult population of Tamil Nadu. The overall community prevalence of STDs including HIV and hepatitis B in Tamil Nadu was 14.6% (CI: 14.1-15.1), and 8.3% (CI: 7.9-8.6) when HIV and hepatitis B were excluded. Community prevalence of HIV and hepatitis B infection was 1.8% (CI:1.7-1.9) and 5.3% (CI: 5.1-5.5), respectively. The distribution of HIV involved both rural and urban regions of Tamil Nadu. On clinical examination, at least one STD syndrome was noted in 486 (24.5%) of the women subjects; vaginal discharge was the most common and found in 421 women (38.4%). CONCLUSION: The prevalence of STD and HIV in Tamil Nadu is higher than expected and has extended into the non-high risk population (generalized epidemic).

Pre-transplant risk factors for renal allograft dysfunction at one year in Indian patients.

BACKGROUND: Only a few patients with end-stage renal disease in the Indian subcontinent receive optimal treatment. Of these only a minority can afford a second renal transplant. Awareness of modifiable pre-transplant risk factors that influence allograft function is crucial before embarking on the first transplant. There are no reports from the Asian subcontinent describing the pre-transplant risk factors. METHODS: We studied the effect of donor age, gender, and relation with the recipient, patient age, gender, HLA matching, native kidney disease and immunosuppression on one-year allograft function using data from 1177 consecutive primary living related donor renal transplants at the Christian Medical College Hospital, Vellore. We performed a univariate followed by a multivariate analysis using a logistic regression model to calculate the odds ratio for the effect of the above factors on two levels of graft function (serum creatinine > 1.4 mg/dl and > 2 mg/dl) at one year. RESULTS: On univariate analysis, older donors, women donors, mother being the donor, men recipients, < 1 HLA antigen match, cyclosporine-based immunosuppression and patient age between 16 and 40 years were associated with serum creatinine levels > 1.4 mg/dl at one year. Multivariate analysis showed that donor-related factors, namely mother as donor, older donors, and a < or = 1 HLA antigen match, were risk factors for graft dysfunction (serum creatinine level > 1.4 mg/dl) at one year. Recipient-related risk factors were male patients and those between the age of 16 and 40 years. CONCLUSION: In patients undergoing living related donor renal transplants from large extended families, a younger haplomatched donor, for instance, a brother, is a better choice than an older haplomatched donor, for instance, the mother, particularly in young male recipients at a higher risk of renal dysfunction.

Randomized controlled trial on the effective dose of anti-snake venom in cases of snake bite with systemic envenomation.

Snake bite is the common cause of morbidity and mortality in India. Snake antivenom, although very effective, is expensive, scarce, and associated with side effects. The conventional dose may not be required in all cases and a smaller dose may be as effective. A randomized double blind controlled trial was conducted to compare the effect of lower versus the conventional (high) dose. Patients presenting within 24 hours of snake bite with hematological or neurological evidence of systemic envenomation were included in the study. Patients were randomized either to receive high dose (2 vials over 1 hour, followed by 2 vials over 4 hours and repeated 4 hourly until clotting parameters normalized and then 2 vials as infusion over 24 hours) or low dose (2 vials over 1 hour, followed by 1 vial over four hours, repeated 4 hourly until clotting parameters were normalized and then 1 vial as an infusion over 24 hours). Thirty one patients received high dose and 29 a low dose. The mean dose of antivenom used was significantly different in the two groups (8.9 and 4.7, respectively). There was no mortality. The duration of stay was 4.94 and 3.48 days, respectively. There was no difference in the transfusion, dialysis or ventilation requirement of the two groups. Low dose regimen is more effective and required 5 vials less than the conventional dose. Each vial costs Rs. 200, so the estimated savings is Rs. 1000 per patient.

A randomised control trial on sequential drug monotherapy versus conventional step care therapy in the treatment of mild to moderate hypertension.

OBJECTIVES: There are many studies in the literature on single drug therapy (monotherapy) for mild to moderate hypertension. These studies show comparable efficacy, side effect profile and compliance. It has not been shown yet, whether the number of patients controlled on monotherapy can be improved by systematically stopping a drug which does not adequately control blood pressure and starting another drug in a sequential manner until blood pressure is well controlled. The aim is to show that sequential drug monotherapy (SDM) is as good as step care therapy (SCT) in controlling mild to moderate hypertension. METHODS: Patients attending three medical outpatient departments of Christian Medical College and Hospital, with mild to moderate hypertension uncontrolled on single drug therapy formed the patient population. They were then randomised to the sequential drug monotherapy or step care therapy. The choice of one of the five antihypertensive drugs was left to the attending physician. RESULTS: Thirty two and 42 patients entered the study and 28 and 35 completed the study in SCT and SDM group, respectively. Follow up was for a period of three months. BP was controlled 100% each in SCT and SDM groups. Efficacy with intention to treat was 85.2% in SCT and 81.8% in SDM group. Percent controlled with second drug was 82 and 71, controlled with third drug was 18 and 14 in SCT and SDM, respectively. Mean duration of treatment for control for BP was 1.7 and 2.3 months in SCT and SDM groups respectively. Average cost in SCT was Rs 66.28 and in SDM was Rs 45.53 per month (p = 0.005). Incidence of ADR was 28.6% and 10.5% in SCT and SDM groups, respectively (p = 0.06). CONCLUSIONS: SDM is as effective as SCT, SDM offers the following advantages: less expensive, better compliance, fewer complications, drug interaction and thus improved quality of life.