No abstract

Despite their clinical efficacy, concerns about calcineurin inhibitor (CNI) toxicity make alternative regimens that reduce CNI exposure attractive for renal transplant recipients. In this systematic review and meta-analysis, we assessed four CNI immunosuppression strategies (minimization, conversion, withdrawal, and avoidance) designed to reduce CNI exposure and assessed the impact of each on patient and allograft survival, acute rejection and renal function. We evaluated 92 comparisons from 88 randomized controlled trials and found moderate- to high-strength evidence suggesting that minimization strategies result in better clinical outcomes compared with standard-dose regimens; moderate-strength evidence indicating that conversion to a mammalian target of rapamycin inhibitor or belatacept was associated with improved renal function but increased rejection risk; and moderate- to high-strength evidence suggesting planned CNI withdrawal could result in improved renal function despite an association with increased rejection risk. The evidence base for avoidance studies was insufficient to draw meaningful conclusions. The applicability of the review is limited by the large number of studies examining cyclosporine-based strategies and low-risk populations. Additional research is needed with tacrolimus-based regimens and higher risk populations. Moreover, research is necessary to clarify the effect of induction and adjunctive agents in alternative immunosuppression strategies and should include more comprehensive and consistent reporting of patient-centered outcomes.

No abstract

Many interventions in medicine, public health, education, social services, behavioral health, and community programs are complex, and they may not fit neatly within the established paradigm for reviews of straightforward interventions. This paper provides conceptual and operational guidance for these early stages of scope formulation to assist authors of systematic reviews of complex interventions.

Patients with secondary progressive MS refractory to conventional medical treatment have longer progression-free survival following autologous stem cell transplantation with intermediate-intensity conditioning regimens than with high-intensity conditioning regimens.