The oxytocin antagonist cligosiban reduces human prostate contractility: Implications for the treatment of benign prostatic hyperplasia.

BACKGROUND AND PURPOSE: With increasing life expectancy, benign prostatic hyperplasia (BPH) consequently affects more ageing men, illustrating the urgent need for advancements in BPH therapy. One emerging possibility may be the use of oxytocin antagonists to relax smooth muscle cells in the prostate, similar to the currently used (although often associated with side effects) α1-adrenoceptor blockers. EXPERIMENTAL APPROACH: For the first time we used live-imaging, combined with a novel image analysis method, to investigate the multidirectional contractions of the human prostate and determine their changes in response to oxytocin and the oxytocin antagonists atosiban and cligosiban. Human prostate samples were obtained and compared from patients undergoing prostatectomy due to prostate cancer as well as from patients with transurethral resection of prostate tissue due to severe BPH. KEY RESULTS: The two cohorts of tissue samples showed spontaneous multidirectional contractions, which significantly increased after the addition of oxytocin. Different to atosiban, which showed ambiguous effects of short duration, only long-acting cligosiban reliably prevented, as well as counteracted, any contractile oxytocin effect. Furthermore, cligosiban visibly reduced not only oxytocin-induced contractions, but also showed intrinsic activity to relax prostatic tissue. CONCLUSION AND IMPLICATIONS: Thus, the oxytocin antagonist cligosiban could be an interesting candidate in the search for novel BPH treatment options.

Improving prehospital traumatic shock care: implementation and clinical effectiveness of a pragmatic, quasi-experimental trial in a resource-constrained South African setting.

OBJECTIVES: This project seeks to improve providers' practices and patient outcomes from prehospital (ie, ambulance-based) trauma care in a middle-income country using a novel implementation strategy to introduce a bundled clinical intervention. DESIGN: We conduct a two-arm, controlled, mixed-methods, hybrid type II study. SETTING: This study was conducted in the Western Cape Government Emergency Medical Services (EMS) system of South Africa. INTERVENTIONS: We pragmatically implemented a simplified prehospital bundle of trauma care (with five core elements) using a novel workplace-based, peer-to-peer, rapid training format. We assigned the intervention and control sites. OUTCOME MEASURES: We assessed implementation effectiveness among EMS providers and stakeholders, using the RE-AIM framework. Clinical effectiveness was assessed at the patient level, using changes in Shock Index x Age (SIxAge). Indices and cut-offs were established a priori. We performed a difference-in-differences (D-I-D) analysis with a multivariable mixed effects model. RESULTS: 198 of 240 (82.5%) EMS providers participated, 93 (47%) intervention and 105 (53%) control, with similar baseline characteristics. The overall implementation effectiveness was excellent (80.6%): reach was good (65%), effectiveness was excellent (87%), implementation fidelity was good (72%) and adoption was excellent (87%). Participants and stakeholders generally reported very high satisfaction with the implementation strategy citing that it was a strong operational fit and effective educational model for their organisation. A total of 770 patients were included: 329 (42.7%) interventions and 441 (57.3%) controls, with no baseline differences. Intervention arm patients had more improved SIxAge compared with control at 4 months, which was not statistically significant (-1.4 D-I-D; p=0.35). There was no significant difference in change of SIxAge over time between the groups for any of the other time intervals (p=0.99). CONCLUSIONS: In this quasi-experimental trial of bundled care using the novel workplace rapid training approach, we found overall excellent implementation effectiveness but no overall statistically significant clinical effectiveness.

Clinical impact of a prehospital trauma shock bundle of care in South Africa.

INTRODUCTION: Patients experiencing traumatic shock are at a higher risk for death and complications. We previously designed a bundle of emergency medical services traumatic shock care ("EMS-TruShoC") for prehospital providers in resource-limited settings. We assess how EMS-TruShoC changes clinical outcomes of critically injured prehospital patients. METHODS: This is a quasi-experimental educational implementation of a simplified bundle of care using a pre-post design with a control group. The intervention was delivered to EMS providers in Western Cape, South Africa. Delta shock index (heart rate divided by systolic blood pressure, reported as change from the scene to facility arrival) from the 13 months preceding intervention were compared to the 13 months post-implementation. A difference-in-differences analysis examined the difference in mean shock index change between the groups. RESULTS: Data were collected from 198 providers who treated 770 severe trauma patients. The patient groups had similar demographic and clinical characteristics at baseline. Over all time-points, both groups had an increase in mean delta shock index (worsening shock), with the largest difference occurring 4-months post-implementation (0.047 change in control arm, 0.004 change in intervention arm; -0.043 difference-in-differences, P = 0.27). In pre-specified subgroup analyses, there was a statistically significant improvement in delta shock index in the intervention arm in patients with penetrating trauma cared for by basic providers immediately post-implementation (-0.372 difference-in-differences, P = 0.02). DISCUSSION: Overall, there was no significant difference in delta shock index between the EMS-TruShoC intervention versus control groups. However, significant improvement in shock index in one subgroup suggests the intervention may be more likely to benefit penetrating trauma patients and basic providers.

Measuring quality of pre-hospital traumatic shock care-development and validation of an instrument for resource-limited settings.

BACKGROUND AND AIMS: Improving the quality of pre-hospital traumatic shock care, especially in low- and middle-income countries, is particularly relevant to reducing the large global burden of disease from injury. What clinical interventions represent high-quality care is an actively evolving field and often dependent on the specific injury pattern. A key component of improving the quality of care is having a consistent way to assess and measure the quality of shock care in the pre-hospital setting. The objective of this study was to develop and validate a chart abstraction instrument to measure the quality of trauma care in a resource-limited, pre-hospital emergency care setting. METHODS: Traumatic shock was selected as the tracer condition. The pre-hospital quality of traumatic shock care (QTSC) instrument was developed and validated in three phases. A content development phase utilized a rapid literature review and expert consensus to yield the contents of the draft instrument. In the instrument validation phase, the QTSC instrument was created and underwent end user and content validation. A pilot-testing phase collected user feedback and performance characteristics to iteratively refine draft versions into a final instrument. Accuracy and inter- and intra-rater agreement were calculated. RESULTS: The final QTSC instrument contains 10 domains of quality, each with specific criteria that determine how the domain is measured and the level of quality of care rendered. The instrument is over 90% accurate and has good inter- and intra-rater reliability when used by trained pre-hospital provider users in South Africa. Pre-hospital provider user feedback indicates the tool is easy to learn and quick to use. CONCLUSION: We created and validated a novel chart abstraction instrument that can reliably and accurately measure the quality of pre-hospital traumatic shock care. We provide a systematic methodology for developing and validating a quality of care tool for resource-limited care settings.