Miliary tuberculosis in human immunodeficiency virus infected patients not on antiretroviral therapy: clinical profile and response to shortcourse chemotherapy

BACKGROUND: An increase in tuberculosis (TB) incidence has been associated with human immunodeficiency virus (HIV). AIMS: To describe the clinical characteristics and treatment outcome of patients with HIV and miliary TB treated with short-course intermittent chemotherapy in the absence of access to highly active antiretroviral therapy (HAART). SETTINGS AND DESIGN: Prospective study of HIV infected adults referred to a TB clinic between July 1999 and July 2004. MATERIALS AND METHODS: On diagnosis of miliary TB, patients were treated with a standard regimen of two months of isoniazid, rifampicin, ethambutol and pyrazinamide followed by four months of isoniazid and rifampicin (2EHRZ 3 /4RH 3 ) thrice weekly and followed up for 24 months. Patients were reviewed clinically every month and two sputa were collected. Chest radiographs and blood investigations were done at two months, end of treatment and every six months thereafter. RESULTS: Of 498 patients with HIV and tuberculosis, 31 (6%) were diagnosed as miliary tuberculosis. At diagnosis, sputum smear was positive for acid-fast bacilli (AFB) in 14 patients (45%) and Mycobacterium tuberculosis was isolated in 21 (68%). The mean CD4 cell count was 129 +/- 125 cells/mm3 . Twenty-five patients were declared cured at the end of treatment (81%) while one (3%) died and five (16%) failed. The recurrence rate was 19.4/100 person-years and the median survival was 17 months (95% CI 14 to 20). None of the patients received antiretroviral therapy. CONCLUSIONS: Miliary TB tends to occur among HIV infected patients with severe immunosuppression. Though the initial response to short-course chemotherapy was encouraging, a high recurrence rate and mortality was observed indicating poor prognosis in HIV.     

Lapatinib nano-delivery systems: a promising future for breast cancer treatment

Introduction: Breast cancer stands the second prominent cause of death among women. For its efficient treatment, Lapatinib (LAPA) was developed as a selective tyrosine kinase inhibitor of receptors, overexpressed by breast cancer cells. Various explored delivery strategies for LAPA indicated its controlled release with enhanced aqueous solubility, improved bioavailability, decreased plasma protein binding, reduced dose and toxicity to the other organs with maximized clinical efficacy, compared to its marketed tablet formulation.

Areas covered: This comprehensive review deals with the survey, performed through different electronic databases, regarding various challenges and their solutions attained by fabricating delivery systems like nanoparticles, micelle, nanocapsules, nanochannels, and liposomes. It also covers the synthesis of novel LAPA-conjugates for diagnostic purpose.

Expert opinion: Unfortunately, clinical use of LAPA is restricted because of its extensive albumin binding capacity, poor oral bioavailability, and poor aqueous solubility. LAPA is marketed as the oral tablet only. Therefore, it becomes imperative to formulate alternate efficient multiparticulate or nano-delivery systems for administration through non-oral routes, for active/passive targeting, and to scale-up by pharmaceutical scientists followed by their clinical trials by clinical experts. LAPA combinations with capecitabine and letrozole should also be tried for breast cancer treatment.     

Novel Endogenous Glycan Therapy for Retinal Diseases: Safety,In Vitro Stability,Ocular Pharmacokinetic Modeling,and Biodistribution

Asialo, tri-antennary oligosaccharide (NA3 glycan) is an endogenous compound, which supports proper folding of outer segment membranes, promotes normal ultrastructure, and maintains protein expression patterns of photoreceptors and Müller cells in the absence of retinal pigment epithelium support. It is a potential new therapeutic for atrophic age-related macular degeneration (AMD) and other retinal degenerative disorders. Herein, we evaluate the safety, in vitro stability, ocular pharmacokinetics and biodistribution of NA3. NA3 was injected into the vitreous of New Zealand white rabbits at two concentrations viz. 1 nM (minimum effective concentration (MEC)) and 100 nM (100XMEC) at three time points. Safety was evaluated using routine clinical and laboratory tests. Ocular pharmacokinetics and biodistribution of [³H]NA3 were estimated using scintillation counting in various parts of the eye, multiple peripheral organs, and plasma. Pharmacokinetic parameters were estimated by non-compartmental modeling. A 2-aminobenzamide labeling and hydrophilic interaction liquid interaction chromatography were used to assess plasma and vitreous stability. NA3 was well tolerated by the eye. The concentration of NA3 in eye tissues was in the order: vitreous > retina > sclera/choroid > aqueous humor > cornea > lens. Area under the curve (0 to infinity) (AUC∞) was the highest in the vitreous thereby providing a positive concentration gradient for NA3 to reach the retina. Half-lives in critical eye tissues ranged between 40 and 60 h. NA3 concentrations were negligible in peripheral organs. Radioactivity from [³H]NA3 was excreted via urine and feces. NA3 was stable at 37°C in vitreous over a minimum of 6 days, while it degraded rapidly in plasma. Collectively, these results document that NA3 shows a good safety profile and favorable ocular pharmacokinetics.

Electronic supplementary material

The online version of this article (doi:10.1208/s12248-014-9563-1) contains supplementary material, which is available to authorized users.Key words: age-related macular degeneration (AMD), NA3 glycan, pharmacokinetics, safety     

SCAI expert consensus update on best practices in the cardiac catheterization laboratory

The current document commissioned by the Society for Cardiovascular Angiography and Interventions (SCAI) and endorsed by the American College of Cardiology, the American Heart Association, and Heart Rhythm Society represents a comprehensive update to the 2012 and 2016 consensus documents on patient-centered best practices in the cardiac catheterization laboratory. Comprising updates to staffing and credentialing, as well as evidence-based updates to the pre-, intra-, and post-procedural logistics, clinical standards and patient flow, the document also includes an expanded section on CCL governance, administration, and approach to quality metrics. This update also acknowledges the collaboration with various specialties, including discussion of the heart team approach to management, and working with electrophysiology colleagues in particular. It is hoped that this document will be utilized by hospitals, health systems, as well as regulatory bodies involved in assuring and maintaining quality, safety, efficiency, and cost-effectiveness of patient throughput in this high volume area.     

Chemometric Models for Quantification of Carbamazepine Anhydrous and Dihydrate Forms in the Formulation

Carbamazepine (CBZ) exists in anhydrous and dihydrate forms. These forms differ in their solubility, dissolution rate, and subsequently in their oral bioavailability. The objective of this study is to develop multivariate chemometric models for estimation of the low level of carbamazepine dihydrate (CBZ-DH) in the CBZ formulations containing excipients of the commercial formulation. The selected excipients were mixed in proportions to make sample matrices ranging from 0% to 50% CBZ-DH. Fourier transform infrared (FTIR), near infrared (NIR), and hyperspectral imaging data were mathematically pretreated before the development of partial least square and principal component analysis regression models. The developed partial least squares regression and principal component analysis models demonstrated predictability of CBZ and CBZ-DH by multiple scattering correction and standard normal variate processing methods. Among the spectroscopic techniques used the model performance parameters such as root-mean-square error, standard error, and bias were found to be low for NIR compared to FTIR. The treated data have shown better model fitting than without treatment, which was demonstrated by correlation coefficient of 0.9778, 0.9824, and 0.9852 for FTIR, NIR, and hyperspectral imaging, respectively. Furthermore, the predicted values were found to be very close to the selected low level of independent samples having 5% CBZ-DH in tablet formulation.