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.

The effect of sham feeding on neurocardiac regulation in healthy human volunteers.

BACKGROUND: Distension and electrical stimuli in the esophagus alter heart rate variability (HRV) consistent with activation of vagal afferent and efferent pathways. Sham feeding stimulates gastric acid secretion by means of vagal efferent pathways. It is not known, however, whether activation of vagal efferent pathways is organ- or stimulus-specific. OBJECTIVE: To test the hypothesis that sham feeding increases the high frequency (HF) component of HRV, indicating increased neurocardiac vagal activity in association with the known, vagally mediated, increase in gastric acid secretion. METHODS: Continuous electrocardiography recordings were obtained in 12 healthy, semirecumbent subjects during consecutive 45 min baseline, 20 min sham feeding (standard hamburger meal) and 45 min recovery periods. The R-R intervals and beat-to-beat heart rate signal were determined from digitized electrocardiography recordings; power spectra were computed from the heart rate signal to determine sympathetic (low frequency [LF]) and vagal (HF) components of HRV. RESULTS: Heart rate increased during sham feeding (median 70.8 beats/min, 95% CI 66.0 to 77.6; P<0.001), compared with baseline (63.6, 95% CI 60.8 to 70.0) and returned to baseline levels within 45 min. Sham feeding increased the LF to HF area ratio (median: 1.55, 95% C.I 1.28 to 1.77; P<0.021, compared with baseline (1.29, 95% CI 1.05 to 1.46); this increase in LF to HF area ratio was associated with a decrease in the HF component of HRV. CONCLUSIONS: Sham feeding produces a reversible increase in heart rate that is attributable to a decrease in neurocardiac parasympathetic activity despite its known ability to increase vagally mediated gastric acid secretion. These findings suggest that concurrent changes in cardiac and gastric function are modulated independently by vagal efferent fibres and that vagally mediated changes in organ function are stimulus- and organ-specific.

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.

Malignant peritoneal mesothelioma in an inguinal hernial sac: an unusual presentation.

Malignant peritoneal mesothelioma, which is a rare neoplasm, usually presents with abdominal complaints. Though such tumours have been reported from tunica vaginalis testis presenting as para-testicular mass, there is only one documented case of the tumour arising from the inguinal hernial sac. In this paper, we are reporting a rare presentation of this tumour.