Combination Intrathecal Drug Therapy Strategies for Pain Management

Background: Numerous combination intrathecal drug therapy (CIDT) strategies exist and are utilized for varying pain syndromes, typically when monotherapy dose escalation or medication alternation is deemed untenable or unfeasible. Unfortunately, the supportive evidence basis for the use of these strategies and specific drug combinations is generally lacking and unclear, with many medications being used for off-label indications. Objective: In this manuscript, we provide a robust exploration and analysis of the literature to provide an evidence-based narrative for the use of CIDT strategies in regard to clinical indications, pharmacologic parameters, specific drug combinations, safety profiles, and future directions. Study design: Narrative review. Methods: This was an evidence based narrative performed after extensive review of the literature. Results: Variances in intrathecal pharmacokinetics and pharmacodynamics are utilized advantageously with CIDT strategies to achieve improved analgesic benefit; however, appropriate use may be limited by increased or compounded risk of adverse effects. The supportive evidence for CIDT use for chronic pain conditions is largely lacking and limited to small, uncontrolled, observational studies, with many having various confounding factors, including a lack of standardized dosing. The most evidenced CIDT strategies include polyanalgesia with morphine-ziconotide, opioid-clonidine, and morphine-bupivacaine. Notably, in addition to pain relief, morphine-bupivacaine has been shown to decrease early opioid escalation requirements. Limitations: The supportive evidence for CIDT use for chronic pain conditions is largely lacking and limited to small, uncontrolled, observational studies, with many having various confounding factors including a lack of standardized dosing. Conclusions: CIDT strategies and polyanalgesia combinations can be effective for treating various patient populations with chronic pain. The appropriate use of these strategies may be limited by increased or compounded risk of adverse effects, both of which are highly patient and scenario dependent. Therefore, practitioners should maintain a particularly low threshold of suspicion for adverse effects in patients with CIDT such that safety profiles associated with this therapy can be favorably maintained

Identifying issues related to integral aspects of collaborative contracts from their stakeholders' perspective

2016 Summer.Includes bibliographical references.Performance in construction is strongly dictated by the processes, technologies, and the people involved. To increase performance, the construction industry has witnessed innovations in project delivery systems - partnering or collaborative contracts is one of those. This thesis focuses on the 'people' part as one of the major factor affecting the performance of a collaborative approach. In this thesis, dispute resolution and incentive provisions have been deemed to be the most vulnerable aspects of construction in which the 'people' part can play an influential role. Collaborative contracts often include a laddered dispute resolution method which includes negotiations as the first few steps and inherently attempts to avoid litigation. Such a process oriented method promotes an inexpensive and non-adversarial approach to dispute resolution. This thesis investigates if such process oriented dispute resolution methods can eliminate the effect of the 'people' part. Moreover, it identifies issues associated with dispute resolution methods and incentive provisions typically found in construction contracts. This thesis also identifies some of the benefits and drawbacks of using an Owner Controlled Insurance Program (OCIP)

Cell-Based Therapies for Rotator Cuff Injuries: An Updated Review of the Literature

This review focuses on non-surgical treatment options for rotator cuff injuries and highlights the potential of mesenchymal stem cells (MSCs) as a potential regenerative approach. MSCs, sourced from various tissues like bone marrow and adipose tissue, exhibit promising mechanisms in vitro, influencing tendon-related gene expression and microenvironment modulation. Animal studies support this, showcasing MSCs’ ability to reduce inflammation, improve tissue remodeling, and enhance repaired tendon strength. Human trials, while varied and limited, suggest that MSCs might lower retear rates and enhance post-repair outcomes, but randomized controlled trials yield mixed results, emphasizing the necessity for standardized investigations. Ultimately, while cell-based therapies demonstrate an excellent safety profile, more rigorous clinical trials are necessary to determine their efficacy in improving patient outcomes and achieving lasting structural changes in rotator cuff injuries