Do geriatrics require dose titration for antidiabetic agents?

OBJECTIVE: To evaluate the antidiabetic drug dosage differences between geriatric and nongeriatric diabetics with reference to duration of disease and creatinine clearance (Crcl). MATERIALS AND METHODS: Prospective study conducted for 6 months in a tertiary care hospital. Patients with type 2 diabetes mellitus were grouped into geriatric (age ≥60 years) and nongeriatric (age <60 years). Patients' demographic data, duration of diabetes, medication, and serum creatinine were recorded. Crcl was calculated using Cockcroft-Gault formula. Doses of sulfonylureas (SU) were converted into equivalent doses, taking glibenclamide as standard. Univariate analysis was done for comparison of drug doses between groups. RESULT: A total of 320 geriatric and 157 nongeriatric diabetics completed the study. The duration of diabetes and Crcl adjusted dose reduction of glibenclamide (mean dose: Geriatrics 7.2±0.4 mg, nongeriatrics 9.6±0.7 mg; P=0.01) and gliclazide (mean dose: Geriatrics 85.5±11.5 mg, nongeriatrics 115.3±32.7 mg; P=0.42) was 25%, glimepiride (mean dose: Geriatrics 1.62±0.13 mg, nongeriatrics 2.1±0.18 mg; P=0.06) was 22%. Glipizide did not require dose reduction. Mean converted equivalent dose of sulfonylurea monotherapy was significantly lower in geriatrics than nongeriatrics (3.2±0.5 vs 6.4±1.02 mg; P=0.01) and showed 50% dose reduction. Mean dose of metformin was lower in geriatrics (901±32.2 mg vs 946.7±45.8 mg; P=0.45) and showed 5% reduction in dosage. There was no difference in the mean drug doses of thiazolidinediones and insulin between the groups. CONCLUSION: A substantial dose reduction of glibenclamide (25%), gliclazide (25%), glimepiride (22%), and metformin (5%) in geriatrics compared to nongeriatrics was observed. Smaller dosage formulations like 0.75 mg glibenclamide, 0.5 mg glimepiride, 20 mg gliclazide, and 250 mg metformin may be of value in geriatric diabetic practice.

Safety and radiosensitizing efficacy of sanazole (AK 2123) in oropharyngeal cancers: randomized controlled double blind clinical trial.

UNLABELLED: Oropharynx is an important site of cancer in India. Global comparison indicates higher incidences in India. Radiotherapy remains an important treatment modality. Efforts to improve loco-regional treatment and prolong survival are areas of focus. Radiosensitizers in hypoxic tumors have shown promise. AIM: To study the safety and radiosensitizing efficacy of sanazole in oropharyngeal squamous cell carcinoma (stage T2-4, N0-3, M0) as phase-II double blind controlled trial in patients treated with conventional radiotherapy. SETTINGS AND DESIGN: Single institutional, randomized, double-blind, placebo-controlled trial. MATERIALS AND METHODS: Group 1 (control; n = 23) received normal saline infusion, group 2 (test; n = 23) received sanazole biweekly 1.25 g intravenous infusion 15 minutes before radiotherapy. Surrogate end points of efficacy were tumor and nodal size; safety parameters were mucositis, salivary and skin reactions, dysphagia, vomiting, dysgeusia and neurological deficit. Investigators blinded to the trial evaluated patients, weekly during treatment for six weeks and thereafter monthly for three months. STATISTICAL METHODS: Non-parametric, Friedman's, Chi square, Mann-Whitney U tests. RESULTS: In the test, 15 (65%) patients had complete response, five (22%) partial/no response, two (9%) died, one (4%) lost to follow up. In the control, five (22%) patients had complete response, 16 (70%) partial/no response, one (4%) died, one (4%) lost to follow up. Short-term loco-regional response was better in the test (DF = 3, 95% Confidence Interval 0.418, 0.452, P = 0.0048). In the test group significant vomiting and one case of grade 3 neurological deficit was observed. CONCLUSION: The study validates the usefulness of sanazole for initial loco-regional control in oropharyngeal cancers.

An open comparative clinical trial to assess the efficacy and safety of losartan versus enalapril in mild to moderate hypertension.

OBJECTIVES: To compare the efficacy and safety of losartan with enalapril, in mild to moderate hypertension. METHODS: An open, enalapril controlled study was conducted in 30 patients with mild to moderate hypertension. Losartan 50 mg was administered to patients for eights weeks. Throughout the study blood pressure was measured every two weeks. Routine laboratory investigations were performed before entering the trial, fourth week and at the end of the study. Adverse effects were recorded. After eight weeks losartan was stopped and enalapril 10 mg daily was administered to the same patients after two weeks washout period. The same methodology that was followed for losartan trial was repeated for enalapril trial also. RESULTS: Losartan treatment resulted in a highly significant reduction in the mean sitting diastolic blood pressure. Comparison with enalapril showed that both drugs are equally efficacious in reducing blood pressure in mild to moderate hypertension. The percentage of responders was slightly more with losartan than enalapril (86.7% vs 76.7%). Adverse events reported with losartan were mild. Enalapril also was well tolerated like losartan but there was high incidence of dry cough, which was reported in nine patients (30%). CONCLUSIONS: Losartan is an effective antihypertensive drug with an excellent safety and tolerability profile. It shows similar blood pressure lowering efficacy to that of enalapril. In contrast to enalapril, losartan does not cause dry cough.

Serum C peptide level and renal function in diabetes mellitus.

C peptide is an active peptide hormone with potentially important physiological effects. C peptide has the capacity to diminish glomerular hyperfiltration and reduce urinary albumin excretion in both experimental and human type 1 diabetes. The present study is aimed at correlating the serum C peptide level with that of renal clearance, urinary albumin excretion and duration of diabetes. This is a prospective cross sectional study. Patients with diagnosis of type 2 diabetes mellitus were evaluated for their baseline clinical and laboratory profile. Both males and females above the age of 18 years were included in the study. The laboratory investigations include fasting serum C peptide, HbA(1C), serum creatinine, blood urea nitrogen, urine albumin and creatinine. Creatinine clearance was calculated using modification of diet in renal disease formula from serum creatinine value. A total of 168 patients were included in the study, among them 90 were females (53.57%) and 78 males (46.43%). Mean age of the patients was 57.64 years. Pearson correlation test showed negative correlation of serum C peptide level with creatinine clearance, though statistically not significant. Negative correlation was also seen between serum C peptide, and urine albumin, urine albumin creatinine ratio, HbA(1C) and duration of diabetes. Mean urine albumin was higher in patients with subnormal C peptide level. Duration of disease was more in patients with lower serum C peptide level. The study has shown weak association of serum C peptide level with microalbuminuria and creatinine clearance. Risk of albuminuria is more in patients with low serum C peptide level.

Microalbuminuria in diabetes mellitus: Association with age, sex, weight, and creatinine clearance.

Studies in the Western literature show a linear relationship between degree of microalbuminuria and body mass index (BMI), blood pressure, and duration of diabetes. This study was aimed to determine the correlation of microalbuminuria with age, sex, duration of diabetes, BMI, and creatinine clearance in type-2 diabetics in Indian population. One hundred patients (59 males and 41 females) with type-2 diabetes mellitus of duration six months or more and negative for albumin in urine by albustic method were included in the study. Detailed clinical history was taken followed by a thorough physical examination that included neurological examination in the selected patients. Micral test was used for estimation of microalbuminuria. Overall prevalence of microalbuminuria in the present study was 37%. Among the patients with microalbuminuria, 20 were males and 17 were females. Pearson correlation of microalbuminuria with age showed statistically significant linear relationship. Gender-wise correlation analysis of microalbuminuria failed to show any statistical significance. Correlation of microalbuminuria with BMI was also not significant (r = 0.063, P > 0.05). Creatinine clearance negatively correlated with microalbuminuria, but this was statistically insignificant. There was a statistically significant correlation of microalbuminuria with duration of diabetes. Prevalence of microalbuminuria is around 37% in type-2 diabetes mellitus. Incidence of microalbuminuria increases with age as well as with increased duration of diabetes mellitus. There is no effect of BMI and sex on the prevalence of microalbuminuria.

Study of clinical profile and antibiotic response in typhoid fever.

The objective of the present study is to evaluate the clinical profile and pattern of various drugs used in the treatment of typhoid fever. A retrospective analysis of adult patients suffering from typhoid fever was done at Kasturba Medical College hospital, Attavar during the year 1999-2001. Diagnosis of patients was based on clinical features, widal test and blood culture. The sensitivity pattern of isolates from blood culture was recorded. The mode of presentation, clinical course, treatment history, laboratory investigations reports, antibiotic administered, response to therapy and the complications were recorded. Total number of 44 cases of typhoid fever were studied. Out of these 21(47.7%) were males and 23(52.3%) were females. Average age of presentation was 23.9 years. Average duration of hospital stay was 10.8 days. Fever was present in all patients. Resistance of S. typhi to amoxicillin, chloramphenicol, ampicillin and co-trimoxazole were significantly high. Ciprofloxacin also showed resistance in 18.1% of cases. Sensitivity to cephalosporin was 100% in our study. Ciprofloxacin was the most commonly used antibiotic in our study (23 patients). Chloramphenicol alone was used in 2 patients and in 3 patients it was given after 6 days of ciprofloxacin treatment. Third generation cephalosporins (ceftriaxone) alone were used in 16 patients. Indiscriminate use of drugs in typhoid fever should be discouraged. Appropriate antibiotic as indicated by sensitivity tests should be employed to prevent the development of resistant strains of S. typhi.