A prospective, observational cohort study to elicit adverse effects of antiretroviral agents in a remote resource-restricted tribal population of Chhattisgarh

Objective:

To assess the adverse effects of antiretroviral therapy (HAART) and its adherence in HIV-infected patients, in remote and tribal area with restricted resources.

Materials and Methods:

This was a prospective, observational study carried out at Department of Medicine, Government Medical College, Jagdalpur. A set of questions were asked and adverse drug reactions (ADRs) were recorded for every patient.

Results:

79 HIV positive patients were analyzed. Among them, 68 (86%) had at least one ADR. The mean ADR per patient was 1.64 (±1.09). The most common ADR in our study was peripheral neuropathy (20.83%), followed by skin rashes (15.83%). Twenty-one patients (26.58%) had severe (grade-3 and grade-4) ADRs. Female patients had more ADRs (45.71%) than males (11.36%); severe ADRs had a statistically significant positive correlation with sex and CD4 cell count of the patients.

Conclusion:

In spite of high ADRs, HAART is the only answer to HIV/AIDS; thus, management requires a highly precise balance between benefits of durable HIV suppression and the risks of drug toxicity to achieve the therapeutic goals, with conventional drugs or with newer less toxic agents.     

Live/real time three-dimensional transthoracic echocardiographic identification of quadricuspid aortic valve

We describe an adult in whom live/real time three-dimensional echocardiography was able to make a definite diagnosis of a quadricuspid aortic valve which was misdiagnosed as bicuspid by live two-dimensional transthoracic echocardiography (2DTTE).     

Superior vena cava, right pulmonary artery or both: real time two- and three-dimensional transthoracic contrast echocardiographic identification of the echo-free space posterior to the ascending aorta

We describe the usefulness of contrast echocardiography and live/real time three-dimensional transthoracic echocardiography in characterizing the normal structures imaged posterior to the proximal ascending aorta as superior vena cava, right pulmonary artery, or both.     

Comparison of two- and three-dimensional transthoracic echocardiography in the assessment of trabeculations and trabecular mass in left ventricular noncompaction

Twenty-one patients (mean age 47.5 years, 9 females) with left ventricular noncompaction (LVNC) diagnosed by both two-dimensional transthoracic echocardiography (2DTTE) and live/real time three-dimensional transthoracic echocardiography (3DTTE) were included in the study. Left ventricular (LV) mass was calculated with epicardial and endocardial border tracings first including the LV trabeculations and then excluding them. LV trabecular mass was then derived as the difference between the two measurements. This was done by 2DTTE using the modified biplane Simpson's method and by live/real time 3DTTE using the Tom Tec imaging system. The number of trabeculations arising from each segment of LV walls as well as the segmental distribution of trabeculations were also assessed by both 2DTTE and 3DTTE. The calculated LV trabecular mass by 3DTTE (mean 11.8 +/- 5.5 g) was significantly greater than 2DTTE (mean 7.3 +/- 4.3 g, P = 0.005). The total number of trabeculations assessed by 3DTTE (mean 11.2 +/- 3.3) was also significantly greater than 2DTTE (mean 3.76 +/- 1.2, P < 0.0001). The values for inter- and intraobserver variability were lower for 3DTTE than 2DTTE. In conclusion, both LV trabecular mass as well as the total number of trabeculations in patients with LVNC were significantly underestimated by 2DTTE as compared to 3DTTE.     

Assessment of surgically unroofed coronary sinus by live/real time three-dimensional transthoracic echocardiography

Both two-dimensional transthoracic echocardiography (2DTTE) and live/real time three-dimensional transthoracic echocardiography (3DTTE) were attempted in a 25-year-old morbidly obese female with total anomalous pulmonary venous return (TAPVR) into the coronary sinus (CS) in whom surgical unroofing of CS with patch closure of CS ostium was performed in infancy to redirect pulmonary venous flow into the left atrium (LA). The patient had become increasingly symptomatic over the past 1 year because of severe left-to-right shunting due to dehiscence of the patch used to close the CS ostium. Despite a poor acoustic window, 3DTTE was able to identify a communication between the LA and CS which resulted from surgical unroofing of the CS as well as flow signals moving into the right atrium from the CS. These findings were not detected by 2DTTE.     

Formulation development of ambroxol hydrochloride soft gel with application of statistical experimental design and response surface methodology

The purpose of present work was to develop ambroxol hydrochloride soft gel formulation with the application of statistical experimental design and response surface methodology (RSM). A two-factor, three-level (3(2)) full factorial design of experiment with RSM was run to evaluate the main and interaction effect of two independent formulation variables that included the amount of low-acetylated gellan gum and sodium citrate. The dependent variables included viscosity (Y(1)), amount of drug release at 10 min (Y(2)) and 30 min (Y(3)), and gelation time (Y(4)). In order to obtain a formulation having the maximum amount of drug release at 10 min and minimum gelation time, RSM optimization was used. The prepared formulations were evaluated for pH, viscosity, rheological properties, gelation time, drug content, in vitro drug release, appearance, and taste. All the formulations showed a gelation time in the range of 6 to 48 min. The drug content in all the formulations was within limit (99.6 ± 1.56%). The viscosity of all the formulations was found in the range of 1872-12,182 cP. Dissolution studies of the formulations showed drug release in the range of 40.56-72.46% within 10 min and 80.2-100.5% within 30 min. Human evaluation tests revealed that all the gels possessed acceptable characteristics. This study showed that the soft gel formulation GA5, containing 0.3% of gellan gum and 0.4% of sodium citrate, has potential use as an immediate release soft gel for oral drug delivery. LAY ABSTRACT: The objective of this investigation was to develop a new, immediate-release, soft gel dosage form for ambroxol hydrochloride, an oral expectorant and mucolytic agent. This novel soft gel dosage form needs to be suitable for pediatric and geriatric patients as well as patients with dysphagia. A statistical technique was used for optimization of the gel formulation. The methodology, called a design of experiment with response surface methodology, evaluated several independent formulation variables, including the amount of two ingredients, low-acetylated gellan gum and sodium citrate. Their effects were studied by comparing physical properties of the gel such as viscosity, amount of drug release at 10 and 30 min, and gelation time. The final optimized formulation (0.3% of gellan gum and 0.4% of sodium citrate) was chosen to maximize the amount of drug release at 10 min, minimize gelation time, and optimize viscosity in a reasonable range. After this optimization exercise, the prepared ambroxol hydrochloride soft gel formulations were evaluated for pH, viscosity, rheological properties, gelation time, drug content, in vitro drug release, appearance, and taste. Human evaluation tests revealed that all the gels possessed acceptable organoleptic characteristics.     

Toward an integrated knowledge environment to support modern oncology

Around the world, teams of researchers continue to develop a wide range of systems to capture, store, and analyze data including treatment, patient outcomes, tumor registries, next-generation sequencing, single-nucleotide polymorphism, copy number, gene expression, drug chemistry, drug safety, and toxicity. Scientists mine, curate, and manually annotate growing mountains of data to produce high-quality databases, while clinical information is aggregated in distant systems. Databases are currently scattered, and relationships between variables coded in disparate datasets are frequently invisible. The challenge is to evolve oncology informatics from a "systems" orientation of standalone platforms and silos into an "integrated knowledge environments" that will connect "knowable" research data with patient clinical information. The aim of this article is to review progress toward an integrated knowledge environment to support modern oncology with a focus on supporting scientific discovery and improving cancer care.