Pharmacokinetics of bedaquiline in cerebrospinal fluid (CSF) in patients with pulmonary tuberculosis (TB).

BACKGROUND: With current treatment options most patients with CNS TB develop severe disability or die. Drug-resistant tuberculous meningitis is nearly uniformly fatal. Novel treatment strategies are needed. Bedaquiline, a potent anti-TB drug, has been reported to be absent from CSF in a single report. OBJECTIVES: To explore the pharmacokinetics of bedaquiline and its M2 metabolite in the CSF of patients with pulmonary TB. PATIENTS AND METHODS: Individuals with rifampicin-resistant pulmonary TB established on a 24 week course of treatment with bedaquiline underwent a lumbar puncture along with multiple blood sample collections over 24 h for CSF and plasma pharmacokinetic assessment, respectively. To capture the expected low bedaquiline and M2 concentrations (due to high protein binding in plasma) we optimized CSF collection and storage methods in vitro before concentrations were quantified via liquid chromatography with tandem MS. RESULTS: Seven male participants were enrolled, two with HIV coinfection. Using LoBind® tubes lined with a 5% BSA solution, bedaquiline and M2 could be accurately measured in CSF. Bedaquiline and M2 were present in all patients at all timepoints at concentrations similar to the estimated unbound fractions in plasma. CONCLUSIONS: Bedaquiline and M2 penetrate freely into the CSF of pulmonary TB patients with a presumably intact blood-brain barrier. Clinical studies are urgently needed to determine whether bedaquiline can contribute meaningfully to the treatment of CNS TB.

Homoeopathic eye drops in the treatment of mild-to-moderate dry eye disease: Randomised, prospective, multicentre, single-masked study.

INTRODUCTION: To compare the efficacy and safety of a homeopathic eye drop medicinal product (Homeoptic®) with 0.9% sodium hydrochloride eye drops (Larmabak®) in patients with mild-to-moderate dry eye disease (DED). METHODS: Prospective, single-masked, observer-blinded, multicentre study on adult patients. Non-inferiority primary endpoint of the relative change between treatment groups in a composite Visual Analogue Scale (VAS) score covering five symptoms of DED, namely pain, itching, sensation of dry eye, impression of foreign body presence and burning, after 30 days of treatment. Details of all Adverse Events (AEs) were recorded and analysed. RESULTS: Ninety three patients were randomised to each treatment arm. At Day 30, the mean VAS symptom score was 26.0 ± 18.8 in the Homeoptic® group and 32.8 ± 21.2 Larmabak® group. Homeoptic® was demonstrated to be non-inferior to Larmabak®: the mean treatment difference of -7 being below the 10 mm upper limit of the 95% CI ([-12.9; -1.0]) pre-set as significant. The superiority of Homeoptic® over Larmabak® was then established with detection of a significant difference between the two treatment groups (p = 0.022). Significant differences between the treatment groups in favour of Homeoptic® were also detected in isolated VAS scores for the symptoms dry eye sensation (p = 0.009) and burning (p = 0.004). Results of ocular surface staining tests to estimate corneal and conjunctival damage as well as patient satisfaction were also significantly in favour of Homeoptic®. No new safety concerns were identified. CONCLUSION: Homeoptic® is more effective than Larmabak® at relieving the symptoms of DED and constitutes an effective treatment for mild-to-moderate DED.

Mouse models of preeclampsia with preexisting comorbidities.

Preeclampsia is a pregnancy-specific condition and a leading cause of maternal and fetal morbidity and mortality. It is thought to occur due to abnormal placental development or dysfunction, because the only known cure is delivery of the placenta. Several clinical risk factors are associated with an increased incidence of preeclampsia including chronic hypertension, diabetes, autoimmune conditions, kidney disease, and obesity. How these comorbidities intersect with preeclamptic etiology, however, is not well understood. This may be due to the limited number of animal models as well as the paucity of studies investigating the impact of these comorbidities. This review examines the current mouse models of chronic hypertension, pregestational diabetes, and obesity that subsequently develop preeclampsia-like symptoms and discusses how closely these models recapitulate the human condition. Finally, we propose an avenue to expand the development of mouse models of preeclampsia superimposed on chronic comorbidities to provide a strong foundation needed for preclinical testing.

Tailoring nutrition and cancer education materials for breast cancer patients.

OBJECTIVE: Many breast cancer patients are vulnerable to poor nutritional status and may benefit from nutrition education, but existing materials are not generally tailored to the needs of low-literacy immigrant and minority patients. METHODS: With nutritionist guidance, we developed a nutrition presentation for breast cancer patients. English- (n = 29) and Spanish-speaking (n = 19) patients were recruited from 5 safety-net hospitals, an academic cancer center, and a Latina cancer support organization. Materials were tested using multiple rounds of cognitive interviewing (with an adapted USDA interview guide), followed by study team reviews and modifications, until saturation. RESULTS: Seven rounds of interviews per language were needed. Approximately 25% of interviewees had less than a high school education. Changes included adapting to regional lexicons and resolving vague/confusing phrasing. Specific food examples needed cultural tailoring. Text color coding (red/bad, green/good) was requested. Labeled images enhanced participants' understanding of concepts. Spanish speakers expressed a desire to understand nutrition labeling, and this was emphasized in the Spanish slides. CONCLUSION: Cognitive interviews were an important tool for creating a nutrition curriculum tailored to the needs of low-literacy, mostly immigrant patients. PRACTICE IMPLICATIONS: Cultural and linguistic factors should be considered for nutritional education materials in diverse patient populations.