Bedaquiline has potential for targeting tuberculosis reservoirs in the central nervous system

Bedaquiline (BDQ) is the first-in-class United States Food and Drug Administration (US FDA) approved anti-tuberculosis (anti-TB) drug, which is a novel diarylquinoline antibiotic that has recently been utilized as an effective adjunct to existing therapies for multidrug-resistant tuberculosis (MDR-TB). BDQ is especially promising due to its novel mechanism of action, activity against drug-sensitive and drug-resistant tuberculosis (TB) in addition to having the potential to shorten treatment duration. Drug delivery to the central nervous system (CNS) is a major concern in TB chemotherapy, especially with the increasing cases of CNS-TB. In this study, we investigated the CNS penetration of BDQ in healthy rodent brain. Male Sprague-Dawley rats (n = 27; 100 ± 20 g) received a single 25 mg kg⁻¹ b.w dose of BDQ via intraperitoneal (i.p.) administration, over a 24 h period. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine whole tissue drug concentrations and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) was utilized to evaluate drug distribution in the brain. BDQ reached peak concentrations (C_max) of 134.97 ng mL⁻¹ in the brain at a T_max of 4 h, which is within the range required for therapeutic efficacy. BDQ was widely distributed in the brain, with a particularly high intensity in the corpus callosum and associated subcortical white matter including the striatal, globus pallidus, corticofugal pathways, ventricular system, basal forebrain region and hippocampal regions. Using MALDI MSI, this study demonstrates that due to BDQ''s distribution in the brain, it has the potential to target TB reservoirs within this organ.

Bedaquiline (BDQ) was administered to healthy Sprague-Dawley rats in order to determine its localisation in the brain using mass spectrometry imaging (MSI). This study shows that BDQ has the potential for targeting TB reservoirs in the CNS.     

The Impact of Economic Pressure on Parent Positivity,Parenting, and Adolescent Positivity into Emerging Adulthood

This study describes how positivity can be incorporated into the family stress model to explain resilience to disrupted family processes in the face of economic distress. Prospective, longitudinal data came from 451 mothers, fathers, and youth participating from their adolescence through early adulthood. Assessments included observational and self‐report measures. Information regarding economic pressure, parental positivity, and parenting were collected during early adolescence, positivity was collected in late adolescence and emerging adulthood. Results indicated that economic pressure was indirectly associated with adolescent positivity through parental positivity. Economic pressure was negatively associated with parent positivity, whereas parental positivity was positively associated with parenting. Moreover, parental positivity and parenting were related to positivity in adolescence. Results suggest that personal resources linked to a positive outlook can foster nurturant parenting, even in times of economic strain. Such parenting seems to positively influence adolescent development into emerging adulthood.     

A Study of the Use of Psychopharmacologic Agents by Acutely Medically Ill Older Adults

ABSTRACT

This retrospective study sought to investigate issues related to the safety of psychopharmacological agents used by acutely medically ill hospitalized older adults. It explored if there were any associations between commonly prescribed psychiatric medications that medically ill hospitalized older adults received and adverse events. It also sought to compare the safety of antidepressants, sedative/hypnotics, and antipsychotics, when used as a standing (on a preset schedule) and as needed pro re nata (PRN) basis. The study found that psychopharmacological agents are frequently prescribed for medically ill hospitalized older adults. No statistically significant difference was found as far as safety was concerned. The number of PRN medications that were used, and the total number of medications was associated with increased risk of transfer within the hospital to a higher level of care or transfer upon discharge to long-term-care/rehabilitation or hospice. Overall, the use of psychopharmacological agents did not appear to be related to serious adverse events.     

A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

AIMS

Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition.

METHODS

Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken.

RESULTS

One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m⁻². Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide.

CONCLUSIONS

Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7–14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required.     

Understanding and use of inhaler medication by asthmatics in specialty care in Trinidad: a study following development of Caribbean guidelines for asthma management and prevention

STUDY OBJECTIVES: Following the development of the Caribbean Guidelines for Asthma Care, we examined the utilization of inhaled medications in asthmatic patients in Trinidad, West Indies. SETTING: Chest Clinic, Ministry of Health, Trinidad. PARTICIPANTS: Physician-diagnosed asthmatic patients who attended the Chest Clinic between July 1998 and August 2000. MEASUREMENTS AND RESULTS: A consecutive sample of patients who were > 7 years of age (n = 402) was interviewed about compliance with, understanding of, and use of inhaler medication. The inhaler technique of these patients was directly observed. Inhaled steroid therapy was prescribed in 83% of patients but were prescribed the least in elderly patients (63%) and children (62%). Salbutamol was prescribed in 98% of patients, and ipratropium and sodium cromoglycate were selectively prescribed in elderly men and children, respectively. Only 33% of patients used the inhaler correctly, and children and the elderly were the least efficient in its use. The use of a spacer device was advised in 19% of patients, including only 6% of the elderly patients. Explanations for different inhaler therapies were given to 62% of patients, and 53% of patients could describe these reasons. The reported 40% noncompliance rate among patients in the sample was primarily a result of long waiting periods at the pharmacy (58%) and the personal cost incurred on purchasing the medication (52%). CONCLUSIONS: Educating patients, with a focus on children and the elderly, in inhaler techniques and reinforcing understanding of asthma medications can improve asthma management in Trinidad. Asthma caregivers in the Caribbean should ensure the appropriate dissemination of the guidelines and should outline strategies for their implementation.     

The Selvester 32-point QRS score for evaluation of myocardial infarct size after primary coronary angioplasty

In patients treated successfully with primary angioplasty for a first myocardial infarction, the Selvester 32-point score correlates well with infarct size measured with quantitative thallium-201 perfusion imaging. Therefore, it is a useful parameter for infarct sizing, particularly in patients with anterior infarction or reduced ejection fraction at discharge.