Evaluating Vitamin C in Septic Shock: A Randomized Controlled Trial of Vitamin C Monotherapy.

OBJECTIVES: To determine whether IV vitamin C therapy reduces 28-day mortality in patients with septic shock. DESIGN: Multicenter, double-blinded, randomized controlled trial. SETTING: One academic medical ICU and four community ICUs. PATIENTS: Of 167 adult patients within 24 hours of vasopressor initiation for septic shock, 126 consented to participation, and 124 received study drug and were included in analysis. INTERVENTIONS: IV vitamin C (10 mg/mL in normal saline) administered as a 1,000-mg bolus over 30 minutes followed by continuous infusion of 250 mg/hr for 96 hours or placebo of equal volumes of normal saline. MEASUREMENTS AND MAIN RESULTS: Of 124 subjects receiving study drug and included in analysis, 60 received vitamin C and 64 placebo. The primary outcome of all-cause 28-day mortality (vitamin C, 26.7%; placebo, 40.6%; p = 0.10) was lower in the vitamin C arm but did not reach statistical significance. Initiation of renal replacement therapy was higher in the vitamin C arm (vitamin C, 16.7%; placebo, 3.3%; p = 0.015), as was volume of fluid administration within 6 hours of study drug initiation (vitamin C, 1.07 L; placebo, 0.76 L; p = 0.03). There were no statistically significant differences in other secondary outcomes. In post hoc subgroup analysis, there was a decrease in 28-day mortality in the vitamin C arm among patients requiring positive-pressure ventilation at the time of enrollment (vitamin C, 36.3%; placebo, 60.0%; p = 0.05). This trial is registered at clinicaltrials.gov under identifier NCT03338569. CONCLUSIONS: Vitamin C monotherapy failed to significantly reduce mortality in septic shock patients as hypothesized. Our findings do not support its routine clinical use for this purpose.

Why use games for leadership learning?

Why should leadership educators trouble themselves in creating or implementing games for leadership learning? This chapter justifies the use of games as a teaching strategy in leadership education by exploring three rationales. First, games can be meaningfully tied to specific learning theories. Second, games provide motivation for learning, and finally, empirical evidence supports the use of games for leadership learning.

Attitudes toward a novel breastfeeding-mediated drug and nutrient delivery system: A qualitative study.

The objective of this study was to determine the attitudes and impressions of breastfeeding mothers and healthcare practitioners towards a device concept integrating breastfeeding with infant drug and nutrient administration. This was an exploratory qualitative study involving 20 breastfeeding mothers and 6 healthcare practitioners from the Suffolk and Middlesex County areas of Massachusetts, USA each individually interviewed. Interview transcription of the semi-structured interviews by an independent service began during data collection, and data coding into major themes continued until and after data saturation was reached. Repeated medication delivery with a reusable product was highlighted as a potential use case for the device concept; ease of use and cleaning as well as cost, familiarity with the method, and infant response were identified as critical considerations. Participants questioned device suitability with liquid formulations (as opposed to non-liquid), while potential advantages over alternative medication delivery technology like oral syringes were identified, including a more "natural" feeling. Most participants had prior knowledge of, or personal experience with, devices like commercially available nipple shields. Attitudes towards the NSDS were not determined by experience with nipple shields, however. The participants' prior exposure to nipple shields is in contrast to related studies in Kenya and South Africa where commercial nipple shields were not widely known and where specific concerns surrounding potential community stigma to an unknown device were raised by participants.

Different models of pharmaceutical services and care in primary healthcare clinics in the Eastern Cape, South Africa: Challenges and opportunities for pharmacy practice.

BACKGROUND: Primary health care (PHC) re-engineering forms a crucial part of South Africa's National Health Insurance (NHI), with pharmaceutical services and care being crucial to treatment outcomes. However, owing to a shortage of pharmacists within PHC clinics, task-shifting of the dispensing process to pharmacist's assistants and nurses is common practice. The implications of this task-shifting process on the provision of pharmaceutical services and care remains largely unstudied. AIM: The study aimed to explore the pharmacist-based, pharmacist's assistant-based and nurse-based dispensing models within the PHC setting. SETTING: The Nelson Mandela Bay Health District, South Africa. METHODS: A mixed methods approach was utilised comprising of Phase 1: a pharmaceutical services audit to analyse pharmaceutical service provision and Phase 2: semi-structured interviews to describe the pharmaceutical care provision within each dispensing model thematically. RESULTS: Pharmaceutical services partially fulfilled minimum standards within all models, however, challenges exist that limit the quality of these services. Phase 2 showed that the provision of pharmaceutical care within all models was restricted by context-related constraints, thus patient-centred activities to underpin pharmaceutical services were limited. CONCLUSION: Although pharmaceutical services may have been available for all models, compromised quality of these services impacted overall quality of care. Limited pharmaceutical care provision was evident within each dispensing model. The results raised concerns about the current utilisation of pharmacy personnel, including the pharmacist, within the PHC setting. Further opportunities exist, if constraints allow, for the pharmacist to contribute to better patient-centred care.

Clinical and Sociocultural Factors Associated With Failure to Escalate Care of Deteriorating Patients.

In-hospital medical emergencies occur frequently. Understanding how clinicians respond to deteriorating patients outside the intensive care unit (ICU) could improve "rescue" interventions and rapid response programs. This was a qualitative study with interviews with 40 clinicians caring for patients who had a "Code Blue" activation or an unplanned ICU admission at teaching hospitals over 7 months. Four study physicians independently analyzed interview transcripts; refined themes were linked to the transcript using text analysis software. Nine themes were found to be associated with clinicians' management of deteriorating patients. Multiple human biases influence daily care for deteriorating hospitalized patients. A novel finding is that "moral distress" affects escalation behavior for patients with poor prognosis. Most themes indicate that ward culture influences clinicians to wait until the last minute to escalate care despite being worried about the patients' condition.

A phase I study of pivaloyloxymethyl butyrate, a prodrug of the differentiating agent butyric acid, in patients with advanced solid malignancies.

Pivaloyloxymethyl butyrate (AN-9), an acyloxyalkyl ester prodrug of butyric acid (BA), has demonstrated greater potency than BA at inducing malignant cell differentiation and tumor growth inhibition and has demonstrated more favorable toxicological, pharmacological, and pharmaceutical properties than BA in preclinical studies. The principal objective of this study was to determine the feasibility of administering AN-9 as a 6-h i.v. infusion daily for 5 days every 3 weeks in patients with advanced solid malignancies. The study also sought to determine the principal toxicities and maximum tolerated dose of AN-9 on this intermittent schedule, as well as the effects of AN-9 on fetal hemoglobin production, a parameter indicative of RBC differentiation. None of the 28 patients treated with 85 total courses of AN-9 at dosages ranging from 0.047 to 3.3 g/m(2)/day every 3 weeks experienced dose limiting toxicity. Mild to moderate nausea, vomiting, hepatic transaminase elevation, hyperglycemia, fever, fatigue, anorexia, injection site reaction, diarrhea, and visual complaints were observed. Dose escalation of AN-9 was limited by the maximum feasible volume of its intralipid formulation vehicle that could be administered safely on this schedule, resulting in a maximum deliverable dose of 3.3 g/m(2)/day. There was no consistent increase in fetal hemoglobin with AN-9 treatment. A partial response was observed in a previously untreated patient with metastatic non-small cell lung cancer. Additional disease-directed clinical evaluations of AN-9 are necessary to establish the breadth of its antitumor activity and to assess its role as an effective differentiating agent.

Different models of pharmaceutical services and care in primary healthcare clinics in the Eastern Cape, South Africa: challenges and opportunities for pharmacy practice

Background: Primary health care (PHC) re-engineering forms a crucial part of South Africa's National Health Insurance (NHI), with pharmaceutical services and care being crucial to treatment outcomes. However, owing to a shortage of pharmacists within PHC clinics, task-shifting of the dispensing process to pharmacist's assistants and nurses is common practice. The implications of this task-shifting process on the provision of pharmaceutical services and care remains largely unstudied. Aim: The study aimed to explore the pharmacist-based, pharmacist's assistant-based and nurse-based dispensing models within the PHC setting. Setting: The Nelson Mandela Bay Health District, South Africa. Methods: A mixed methods approach was utilised comprising of Phase 1: a pharmaceutical services audit to analyse pharmaceutical service provision and Phase 2: semi-structured interviews to describe the pharmaceutical care provision within each dispensing model thematically. Results: Pharmaceutical services partially fulfilled minimum standards within all models, however, challenges exist that limit the quality of these services. Phase 2 showed that the provision of pharmaceutical care within all models was restricted by context-related constraints, thus patient-centred activities to underpin pharmaceutical services were limited. Conclusion: Although pharmaceutical services may have been available for all models, compromised quality of these services impacted overall quality of care. Limited pharmaceutical care provision was evident within each dispensing model. The results raised concerns about the current utilisation of pharmacy personnel, including the pharmacist, within the PHC setting. Further opportunities exist, if constraints allow, for the pharmacist to contribute to better patient-centred care