The Perfect Step is the first one: Improving the quality of life for patients with spinal cord injuries through structured exercise.

CONTEXT: More than 1 million people live with spinal cord injuries (SCI) in the United States alone. Despite research suggesting improvement in functional activities in patients who participate in regular physical activity, there is limited data on the specific impact of exercise as it pertains to patient-reported quality-of-life (QoL) measures of mood, pain, independence, or medical complications. Patients with SCI participating in a longitudinal exercise program at a community-based fitness facility (The Perfect Step) in Pomona, California were invited to participate in this study. This program consisted of at least two hours a week of exercise-based therapy, loadbearing, and neuroplasticity retraining for two years. Participants were asked to retrospectively rate patient-reported quality-of-life outcomes at the start of participation in the program, and at 6, 12, and 24 months after the program start as measured by an 89-item SCI QoL questionnaire covering domains including mood (39 items), pain (16 items), independence (7 items), bladder function (14 items), and pressure ulcers (13 items). 24 patients with SCI (16 cervical, 4 thoracic, 3 lumbar, 1 unspecified) were included in the final analysis. FINDINGS: Wilcoxon rank sum tests were used to compare patient-reported outcome measures over time. Patients reported statistically significantly improved outcomes across all domains at all timepoints to varying degrees, with improvement in 73/89 items at 6 months, 57/89 at 12 months, and 65/89 at 24 months after participation start (P < 0.05, all). CONCLUSION/CLINICAL RELEVANCE: Patients with SCI engaging in a structured exercise program demonstrated sustainable, longitudinal improvements in mood, pain control, independence, and fewer impairments related to bladder function and pressure ulcers. Physicians should consider the integration of structured exercise into the rehabilitation program alongside traditional medical care to optimize the quality of life for those with SCI. Future research should involve a direct comparison of QoL in patients with SCI participating in structured exercise versus those who are not.

Effects of early exposure to palliative care on end-of-life outcomes in patients with cancer in a community setting.

OBJECTIVE: Although prior studies show that exposure to early outpatient palliative care (OPC) versus no exposure is associated with improved outcomes at the end of life (EoL) for patients with cancer, few examined the impact of exposure to OPC prior to home-based palliative care (HBPC) on EoL outcomes. This study compares the effect of OPC prior to HBPC versus HBPC alone on EoL outcomes in patients with cancer. METHODS: A secondary analysis of data from a trial comparing two models of HBPC was performed on patients with primary cancer diagnoses. Adjusted negative binomial and logistic regression models were used to compare days in acute care and intensive care unit stays in the last 30 days, chemotherapy administration in the last 14 days and in-hospital deaths between patients who received standard-dose (4+ encounters) and low-dose (<4 encounters) OPC plus HBPC versus HBPC alone. RESULTS: A total of 1187 patients, 483 (40.1%) of whom had OPC+HBPC and 704 (59.3%) who had HBPC alone were included in the analyses. Compared with patients who had HBPC alone, patients who had standard-dose OPC spent fewer days in acute care (4.29 vs 4.19, p=0.04) and fewer days inpatient (3.45 vs 3.09, p=0.03) in the last 30 days of life. No difference was seen in EoL outcomes in patients exposed to low-dose OPC compared with those with HBPC alone. Receipt of hospice after HBPC was strongly associated with improved EoL outcomes. CONCLUSION: Future research is needed to examine the modality, timing and intensity of palliative care necessary to effect EoL outcomes.

Primary Addiction Medicine Skills for Hospice and Palliative Medicine Physicians: A Modified Delphi Study.

CONTEXT: Hospice and palliative medicine (HPM) physicians frequently care for patients with substance use disorders (SUDs), but there is no consensus on which primary addiction medicine (AM) skills are essential. OBJECTIVES: Identify key primary AM skills that physicians should acquire during an ACGME-accredited HPM fellowship program. METHODS: A modified Delphi study consisting of 18 experts on SUD in HPM and medical education. A literature review and expert input identified initial AM skills. In three Delphi rounds, participants rated each skill on a nine-point scale from "not at all important to include" to "crucial to include." We calculated medians (IQRs), analyzed panelists' comments, and grouped skills using the RAND / UCLA appropriateness method. RESULTS: Among 62 proposed AM skills, 53 skills were rated as appropriate to include (38 of which achieved agreement), and nine skills were rated as uncertain. AM skills most relevant to HPM included 1) defining chemical coping, median 8.5 (IQR 2); 2) balancing life expectancy with risks of opioid use for patients with SUD, 9 (IQR 0); 3) explaining best practices to dispose unused opioids postmortem, 8 (IQR 2); 4) managing pain for hospice patients with SUD, 9 (IQR 0.75); and 5) partnering with hospice to manage patients on methadone and buprenorphine, 9 (IQR 2). Experts did not achieve consensus on whether HPM physicians should be encouraged to learn to prescribe buprenorphine for patients with opioid use disorder, 6 (IQR 3). CONCLUSION: HPM fellowships should consider incorporating the primary AM skills identified in this study in their curricula.

Implementation of the Helping Babies Breathe Training Program: A Systematic Review.

CONTEXT: Helping Babies Breathe (HBB) is a well-established neonatal resuscitation program designed to reduce newborn mortality in low-resource settings. OBJECTIVES: In this literature review, we aim to identify challenges, knowledge gaps, and successes associated with each stage of HBB programming. DATA SOURCES: Databases used in the systematic search included Medline, POPLINE, Cumulative Index to Nursing and Allied Health Literature, Latin American and Caribbean Health Sciences Literature, African Index Medicus, Cochrane, and Index Medicus. STUDY SELECTION: All articles related to HBB, in any language, were included. Article quality was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation framework. DATA EXTRACTION: Data were extracted if related to HBB, including its implementation, acquisition and retention of HBB knowledge and skills, changes in provider behavior and clinical care, or the impact on newborn outcomes. RESULTS: Ninety-four articles met inclusion criteria. Barriers to HBB implementation include staff turnover and limited time or focus on training and practice. Researchers of several studies found HBB cost-effective. Posttraining decline in knowledge and skills can be prevented with low-dose high-frequency refresher trainings, on-the-job practice, or similar interventions. Impact of HBB training on provider clinical practices varies. Although not universal, researchers in multiple studies have shown a significant association of decreased perinatal mortality with HBB implementation. LIMITATIONS: In addition to not conducting a gray literature search, articles relating only to Essential Care for Every Baby or Essential Care for Small Babies were not included in this review. CONCLUSIONS: Key challenges and requirements for success associated with each stage of HBB programming were identified. Despite challenges in obtaining neonatal mortality data, the program is widely believed to improve neonatal outcomes in resource-limited settings.

Potent, Irreversible Inhibition of Human Carboxylesterases by Tanshinone Anhydrides Isolated from Salvia miltiorrhiza ("Danshen").

The roots of Salvia miltiorrhiza ("Danshen") have been used in Chinese herbal medicine for centuries for a host of different conditions. While the exact nature of the active components of this material are unknown, large amounts of tanshinones are present in extracts derived from these samples. Recently, the tanshinones have been demonstrated to be potent human carboxylesterase (CE) inhibitors, with the ability to modulate the biological activity of esterified drugs. During the course of these studies, we also identified more active, irreversible inhibitors of these enzymes. We have purified, identified, and synthesized these molecules and confirmed them to be the anhydride derivatives of the tanshinones. These compounds are exceptionally potent inhibitors ( Ki < 1 nM) and can inactivate human CEs both in vitro and in cell culture systems and can modulate the metabolism of the esterified drug oseltamivir. Therefore, the coadministration of Danshen extracts with drugs that contain the ester chemotype should be minimized since, not only is transient inhibition of CEs observed with the tanshinones, but also prolonged irreversible inhibition arises via interaction with the anhydrides.

Selective Inhibitors of Human Liver Carboxylesterase Based on a ß-Lapachone Scaffold: Novel Reagents for Reaction Profiling.

Carboxylesterases (CEs) are ubiquitous enzymes that are responsible for the metabolism of xenobiotics, including drugs such as irinotecan and oseltamivir. Inhibition of CEs significantly modulates the efficacy of such agents. We report here that ß-lapachone is a potent, reversible CE inhibitor with Ki values in the nanomolar range. A series of amino and phenoxy analogues have been synthesized, and although the former are very poor inhibitors, the latter compounds are highly effective in modulating CE activity. Our data demonstrate that tautomerism of the amino derivatives to the imino forms likely accounts for their loss in biological activity. A series of N-methylated amino derivatives, which are unable to undergo such tautomerism, were equal in potency to the phenoxy analogues and demonstrated selectivity for the liver enzyme hCE1. These specific inhibitors, which are active in cell culture models, will be exceptionally useful reagents for reaction profiling of esterified drugs in complex biological samples.