Therapeutic drug monitoring of systemic antifungal agents: a pragmatic approach for adult and pediatric patients.

Introduction: Therapeutic drug monitoring (TDM) has been shown to optimize the management of invasive fungal infections (IFIs), particularly for select antifungal agents with a well-defined exposure-response relationship and an unpredictable pharmacokinetic profile or a narrow therapeutic index. Select triazoles (itraconazole, voriconazole, and posaconazole) and flucytosine fulfill these criteria, while the echinocandins, fluconazole, isavuconazole, and amphotericin B generally do not do so. Given the morbidity and mortality associated with IFIs and the challenges surrounding the use of currently available antifungal agents, TDM plays an important role in therapy.Areas covered: This review seeks to describe the rationale for TDM of antifungal agents, summarize their pharmacokinetic and pharmacodynamic properties, identify treatment goals for efficacy and safety, and provide recommendations for optimal dosing and therapeutic monitoring strategies.Expert opinion: Several new antifungal agents are currently in development, including compounds from existing antifungal classes with enhanced pharmacokinetic or safety profiles as well as agents with novel targets for the treatment of IFIs. Given the predictable pharmacokinetics of these newly developed agents, use of routine TDM is not anticipated. However, expanded knowledge of exposure-response relationships of these compounds may yield a role for TDM to improve outcomes for adult and pediatric patients.

Group physical therapy for veterans with knee osteoarthritis: study design and methodology.

Physical therapy (PT) is a key component of treatment for knee osteoarthritis (OA) and can decrease pain and improve function. Given the expected rise in prevalence of knee OA and the associated demand for treatment, there is a need for models of care that cost-effectively extend PT services for patients with this condition. This manuscript describes a randomized clinical trial of a group-based physical therapy program that can potentially extend services to more patients with knee OA, providing a greater number of sessions per patient, at lower staffing costs compared to traditional individual PT. Participants with symptomatic knee OA (n = 376) are randomized to either a 12-week group-based PT program (six 1 h sessions, eight patients per group, led by a physical therapist and physical therapist assistant) or usual PT care (two individual visits with a physical therapist). Participants in both PT arms receive instruction in an exercise program, information on joint care and protection, and individual consultations with a physical therapist to address specific functional and therapeutic needs. The primary outcome is the Western Ontario and McMasters Universities Osteoarthritis Index (self-reported pain, stiffness, and function), and the secondary outcome is the Short Physical Performance Test Protocol (objective physical function). Outcomes are assessed at baseline and 12-week follow-up, and the primary outcome is also assessed via telephone at 24-week follow-up to examine sustainability of effects. Linear mixed models will be used to compare outcomes for the two study arms. An economic cost analysis of the PT interventions will also be conducted.

Non-paretic quadriceps activity influences paretic quadriceps activity post-stroke.

OBJECTIVE: Inappropriate muscle activity is common following stroke. Paretic muscle activation may be influenced by non-paretic volitional activation. We examined the influence of non-paretic quadriceps activation on paretic quadriceps excitability. METHODS: Individuals with chronic stroke performed bilateral and unilateral (paretic and non-paretic) maximum voluntary isometric contractions. Peak torque and muscle activity were compared between conditions. An instrumented tendon tapper elicited a patellar tendon reflex of the relaxed paretic leg while the non-paretic leg was relaxed and pre-activated. The threshold to elicit a paretic quadriceps response was compared between conditions. RESULTS: During the bilateral MVIC, the paretic quadriceps generated less absolute torque, but greater relative torque than the non-paretic side when normalized to the respective unilateral condition (p<0.05). During reflex testing, the tendon tapping threshold to elicit paretic muscle and torque responses decreased with non-paretic activity (p<0.05). CONCLUSIONS: Concurrent non-paretic activation resulted in a relative disinhibition of the paretic quadriceps. The paretic limb's inability to remain inactive during isolated non-paretic contractions implies increased excitation or decreased inhibition of paretic motor pools, although the source remains unknown. SIGNIFICANCE: Unwanted muscle activity during reciprocal tasks (gait training) may be due to contralateral effects of non-paretic muscle activity.