Strategies for isoniazid preventive therapy in HIV-positive patients who consume alcohol.

WHO guidance to defer isoniazid preventive therapy (IPT) among those with regular alcohol use because of hepatotoxicity concerns may exclude many people living with HIV (PLWH) at high TB risk in these settings.To evaluate hepatotoxicity during TB preventive therapy (TPT) in PLWH who report alcohol use in Uganda over 10 years.We developed a Markov model of latent TB infection, isoniazid preventive therapy (IPT - a type of TPT), and TB disease using data from the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) study. We modeled several treatment scenarios, including no IPT, IPT with liver enzyme monitoring (AST/ALT) during treatment, and IPT with pre-screening using the tuberculin skin test (TST).The no IPT scenario had 230 TB deaths/100,000 population over 10 years, which is more than that seen in any IPT scenario. IPT, even with no monitoring, was preferred over no IPT when population TB disease incidence was >50 in 100,000.For PLWH who report alcohol use in high TB burden settings, IPT should be offered, ideally with regular AST/ALT monitoring. However, even if regular monitoring is not possible, IPT is still preferable to no IPT in almost every modeled scenario..

Predictive modeling for pituitary adenomas: single center experience in 501 consecutive patients.

BACKGROUND: Personalized postoperative management of patients with pituitary adenomas requires an early risk stratification system. METHODS: We reviewed 501 cases operated between 10/27/2011 and 5/5/2016 by a single neurosurgeon. We determined biochemical remission and tumor resection at 3 months, and biochemical recurrence, tumor recurrence, radiation and reoperation during follow-up. We considered age, gender, tumor diameter, cavernous sinus invasion (CSI) by MRI, diagnostic category (clinical, biochemical and immunohistochemical), and proliferation markers in a Cox proportional hazards model. We built predictive models with the significant parameters and used Kaplan-Meier survival curves for time-dependent analyses. RESULTS: The 501 cases comprised 141 functional and 360 nonfunctional adenomas. Tumor diameter, CSI, and ki-67 index predicted long-term events. Model 1 (CSI, diameter ≥ 2.9 cm and ki-67 > 3%) identified 18 (3.6%) adenomas and predicted persistent hypersecretory syndrome and residual tumor with 98.7% specificity (OR 8.6; CI 3.0-24.7). Model 2 (ki-67 > 3% and CSI) identified 48 (9.6%) adenomas and had 93.1% specificity (OR 3.3; CI 1.8-6.0). Model 3 (ki-67 > 3%, mitoses and p53, former "atypical" adenoma) identified 26 (5.2%) adenomas and had 96.0% specificity (OR 2.3; CI 1.0-5.0). Model 1 best predicted the long-term event-free survival and was strengthened when Knosp 3-4 CSI grades were used. Model 2 better identified the smaller adenomas at risk. Among the WHO 2017 special PA subtypes, patients with silent corticotroph adenoma had a lower event-free survival than ACTH-negative nonfunctional adenomas. CONCLUSION: Use of CSI, ki-67 and tumor diameter in prediction models facilitates tailored surveillance and management of patients with pituitary adenomas.

LOCOMOTION STRATEGIES AND INTENSITY OF SUPPORT REACTIONS AS AN APPROACH TO INDIVIDUALIZATION OF COUNTERMEASURES AGAINST THE NEGATIVE EFFECTS OF MICROGRAVITY.

A search for optimal methods of planning cosmonaut's training is currently guided by the concept of the leading role of support afferentation in hypogravity-induced changes of locomotion. Support afferentation is dependent on the strength of support reactions (SR); in this connection, the investigation was aimed at analysis of the vertical component of maximal SR at identical speeds of different types of locomotion on motorized and nonmotorized treadmill in I g and micro-g. Minimal vertical components of maximal SR were, measured during walk on the motorized treadmill. Maximal vertical components of maximal SR were measured during run on the nonmotorized treadmill. This was observed regularly on ISS treadmill BD-2 outfitted with vibroisolation and a special training suit to produce axial loading. On the ground, the relationship was less regular. Considerable differences of individual locomotion strategies and maximal SR values imply that SR is a factor that must be taken into account when planning individual training programs for rnosmonaut on long-duration missions.