Titanium Dioxide (E171 Grade) and the Search For Replacement Opacifiers and Colorants: Supplier Readiness Survey, Case Studies and Regulatory Perspective.

Titanium dioxide (TiO2) is used primarily as an opacifier in solid dosage forms and is present in the majority of tablet and capsule dosage forms on the market. The IQ* TiO2 Working Group has previously shown that titanium dioxide has unique properties which are necessary for its function in these formulations and noted that, as the potential replacements lack the semi-conductor properties, high refractive index and whiteness of E171, it might be hard to replicate these properties with alternative materials. In this paper we detail the results of readiness surveys and practical assessments that have been conducted with alternative materials by IQ member companies. A range of technical challenges and regulatory hurdles were identified which mean that, in the short term, it may be difficult to replace titanium dioxide with the currently available alternative materials while readily achieving the same drug product quality attributes, especially for some of the marketed formulations that titanium dioxide is currently used for. We note the higher technical complexity, due to the variability, color fading and identified scale up risk, of E171 free film coatings and the likely impact on development costs and timelines. We also highlight several regulatory hurdles that would have to be overcome if a titanium dioxide replacement was required for some markets but was not mandated by others.

Impact of a nurse engagement intervention on pain, agitation and delirium assessment in a community intensive care unit.

BACKGROUND: In 2013, the Society of Critical Care Medicine published a revised version of the ICU Pain, Agitation, and Delirium (PAD) guidelines. Immobility and sleep were subsequently added in 2018. Despite the well-established advantages of implementing these guidelines, adoption and adherence remain suboptimal. This is especially true in community settings, where PAD assessment is performed less often, and the implementation of PAD guidelines has not yet been studied. The purpose of this prospective interventional study is to evaluate the effect of a multifaceted nurse engagement intervention on PAD assessment in a community intensive care unit (ICU). METHODS: All patients admitted to our community ICU for over 24 hours were included. A 20-week baseline audit was performed, followed by the intervention, and a 20-week postintervention audit. The intervention consisted of a survey, focus groups and education sessions. Primary outcomes included rates of daily PAD assessment using validated tools. RESULTS: There were improvements in the number of patients with at least one assessment per day of pain (67.5% vs 59.3%, p=0.04), agitation (93.1% vs 78.7%, p<0.001) and delirium (54.2% vs 39.4%, p<0.001), and the number of patients with target Richmond Agitation-Sedation Scale ordered (63.1% vs 46.8%, p=0.002). There was a decrease in the rate of physical restraint use (10.0% vs 30.9%, p<0.001) and no change in self-extubation rate (0.9% vs 2.5%, p=0.2). CONCLUSION: The implementation of a multifaceted nurse engagement intervention has the potential to improve rates of PAD assessment in community ICUs. Screening rates in our ICU remain suboptimal despite these improvements. We plan to implement multidisciplinary interventions targeting physicians, nurses and families to close the observed care gap.

Qualitative descriptive study to explore nurses' perceptions and experience on pain, agitation and delirium management in a community intensive care unit.

OBJECTIVES: The purpose of this study was to explore the experiences, beliefs and perceptions of intensive care unit (ICU) nurses on the management of pain, agitation and delirium (PAD) in critically ill patients. DESIGN: A qualitative descriptive study. SETTING: This study took place in a community hospital ICU located in a medium size Canadian city. PARTICIPANTS: Purposeful sampling was conducted. Participants included full-time nurses working in the ICU. Forty-six ICU nurses participated. METHODS: A total of five focus group sessions were held to collect data. There were one to three separate groups in each focus group session, with no more than seven participants in each group. There were 10 separate groups in total. A semistructured question guide was used. Thematic analysis method was adopted to analyse the data, and to search for emergent themes and patterns. RESULTS: Three main themes emerged: (1) the professional perspectives on patient wakefulness state, (2) the professional perspectives on PAD management of critically ill patients and (3) the factors impacting PAD management. Nurses have different opinions on the optimal level of patient sedation and felt that many factors, including environmental, healthcare teams, patients and family members, can influence PAD management. This potentially leads to inconsistent PAD management in critically ill patients. The nurses also believed that PAD management requires a multidisciplinary approach including healthcare teams and patients' families. CONCLUSIONS: Many external and internal factors contribute to the complexity of PAD management including the attitudes of nursing staff towards PAD. The themes emerged from this study suggested the need of a multifaceted and multidisciplinary quality improvement programme to optimise the management of PAD in the ICU.

Pain, agitation and delirium assessment and management in a community medical-surgical ICU: results from a prospective observational study and nurse survey.

BACKGROUND: Delirium is a common manifestation in the intensive care unit (ICU) that is associated with increased mortality and morbidity. Guidelines suggested appropriate management of pain, agitation and delirium (PAD) is crucial in improving patient outcomes. However, the practice of PAD assessment and management in community hospitals is unclear and the mechanisms contributing to the potential care gap are unknown. OBJECTIVES: This quality improvement initiative aimed to review the practice of PAD assessment and management in a community medical-surgical ICU (MSICU) and to explore the community MSICU nurses' perceived comfort and satisfaction with PAD management in order to understand the mechanisms of the observed care gap and to inform subsequent quality improvement interventions. METHODS: We prospectively collected basic demographic data, clinical information and daily data on PAD process measures including PAD assessment and target Richmond Agitation-Sedation Scale (RASS) score ordered by intensivists on all patients admitted to a community MSICU for >24 hours over a 20-week period. All ICU nurses in the same community MSICU were invited to participate in an anonymous survey. RESULTS: We collected data on a total of 1101 patient-days (PD). 653 PD (59%), 861 PD (78%) and 439 PD (39%) had PAD assessment performed, respectively. Target RASS was ordered by the intensivists on 515 PD (47%). Our nurse survey revealed that 88%, 85% and 41% of nurses were comfortable with PAD assessment, respectively. CONCLUSIONS: Delirium assessment was not routinely performed. This is partly explained by the discomfort nurses felt towards conducting delirium assessment. Our results suggested that improvement in nurse comfort with delirium assessment and management is needed in the community MSICU setting.