Marijuana Use and Health Outcomes in Persons Living With HIV: Protocol for the Marijuana Associated Planning and Long-term Effects (MAPLE) Longitudinal Cohort Study.

BACKGROUND: Marijuana use is common in persons with HIV, but there is limited evidence of its relationship with potential health benefits or harms. OBJECTIVE: The Marijuana Associated Planning and Long-term Effects (MAPLE) study was designed to evaluate the impact of marijuana use on HIV-related health outcomes, cognitive function, and systemic inflammation. METHODS: The MAPLE study is a longitudinal cohort study of participants living with HIV who were recruited from 3 locations in Florida and were either current marijuana users or never regular marijuana users. At enrollment, participants completed questionnaires that included detailed marijuana use assessments, underwent interviewer-administered neurocognitive assessments, and provided blood and urine samples. Ongoing follow-ups included brief telephone assessments (every 3 months), detailed questionnaires (annually), repeated blood and urine samples (2 years), and linkage to medical records and statewide HIV surveillance data. Supplemental measures related to intracellular RNA, COVID-19, Alzheimer disease, and the gut microbiome were added after study initiation. RESULTS: The MAPLE study completed enrollment of 333 persons between 2018 and 2021. The majority of participants in the sample were ≥50 years of age (200/333, 60.1%), male (181/333, 54.4%), cisgender men (173/329, 52.6%), non-Hispanic Black (221/333, 66.4%), and self-reported marijuana users (260/333, 78.1%). Participant follow-up was completed in 2022, with annual updates to HIV surveillance data through at least 2027. CONCLUSIONS: The MAPLE study is the largest cohort specifically designed to understand the use of marijuana and its effects on HIV-related outcomes. The study population has significant diversity across age, sex, gender, and race. The data will help clinicians and public health officials to better understand patterns of marijuana use associated with both positive and negative health outcomes, and may inform recommendations for future clinical trials related to medical marijuana and HIV. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37153.

Intravenous vitamin C administration to patients with septic shock: a pilot randomised controlled trial.

BACKGROUND: Intravenous vitamin C administration in septic shock may have a sparing effect on vasopressor requirements, and vitamin C's enzyme cofactor functions provide a mechanistic rationale. Our study aimed to determine the effect of intravenous vitamin C administration on vasopressor requirements and other outcomes in patients with septic shock. METHODS: This was a double-blind, randomised placebo-controlled trial in 40 patients with septic shock who were randomised (1:1) to receive intravenous vitamin C (at a dose of 25 mg/kg of body weight every 6 h) or placebo (intravenous 5% dextrose) for up to 96 h, or until death or discharge. The primary outcome was intravenous vasopressor requirements (dose and duration), and secondary outcomes included Sequential Organ Failure Assessment (SOFA) scores, intensive care unit (ICU) and hospital length of stay, and mortality. In addition, blood samples were collected to determine vitamin C kinetics and inflammatory marker concentrations. RESULTS: Median plasma vitamin C concentrations were deficient at baseline (9.2 [4.4, 12] µmol/L) and increased to 408 (227, 560) µmol/L following 72 h of intervention. The mean duration of intravenous vasopressor infusion in the vitamin C group was 48 (95% CI 35-62) hours and in the placebo group was 54 (95% CI 41-62) hours (p = 0.52). The dose of vasopressor delivered over time was comparable between the two groups, as were SOFA scores (p > 0.05). The median ICU length of stay in the intervention group was 3.8 (2.2, 9.8) days versus 7.1 (3.1, 20) days in the placebo group (p = 0.12). The median hospital length of stay for the vitamin C group was 18 (11, 35) days versus 22 (10, 52) days for the placebo group (p = 0.65). Mortality was comparable between the two groups (p > 0.05). Of the inflammatory markers, neutrophil counts were elevated in the vitamin C group relative to placebo by 72 h (p = 0.01). C-reactive protein and myeloperoxidase concentrations were elevated at baseline, however, the two groups were comparable over time (p > 0.05). CONCLUSIONS: Our pilot study indicated that intravenous vitamin C did not provide significant decreases in the mean dose or duration of vasopressor infusion. Further research that takes into account the potential impact of intervention timing, dose and duration, and location of trial, may provide more definitive evidence. TRIAL REGISTRATION: ACTRN12617001184369 (11/8/2017).

Circulating protein carbonyls are specifically elevated in critically ill patients with pneumonia relative to other sources of sepsis.

BACKGROUND: Septic shock is a life-threatening dysregulated response to severe infection and is associated with elevated oxidative stress. We aimed to assess protein carbonyls in critically ill patients with different sources of sepsis and determine the effect of vitamin C intervention on protein carbonyl concentrations. METHODS: Critically ill patients with septic shock (n = 40) were recruited, and sources of sepsis and ICU severity scores were recorded. The patients were randomised to receive either intravenous vitamin C (100 mg/kg body weight/day) or placebo infusions. Blood samples were collected at baseline and daily for up to three days for measurement of cell counts, vitamin C concentrations, protein carbonyls, C-reactive protein, and myeloperoxidase concentrations. RESULTS: Protein carbonyl concentrations increased 2.2-fold in the cohort over the duration of the study (from 169 to 369 pmol/mg protein; p = 0.03). There were significant correlations between protein carbonyl concentrations and ICU severity scores (APACHE III r = 0.47 and SOFA r = 0.37; p < 0.05) at baseline. At study admission, the patients with pneumonia had nearly 3-fold higher protein carbonyl concentrations relative to the patients with other sources of sepsis (435 vs 157 pmol/mg protein, p < 0.0001). The septic patients had deficient vitamin C status at baseline (9.8 ± 1.4 µmol/L). This increased to 456 ± 90 µmol/L following three days of intravenous vitamin C intervention. Vitamin C intervention did not attenuate the increase in protein carbonyl concentrations. CONCLUSIONS: Circulating protein carbonyls are specifically elevated in critically ill patients with pneumonia relative to other sources of sepsis. The reasons for this are currently unclear and may indicate a mechanism unique to pulmonary sources of sepsis. Intravenous vitamin C administration did not attenuate the increase in protein carbonyls over time.

Targeted learning through paediatric simulation

BackgroundSimulation is regularly run with the paediatric multi-disciplinary team at a district general hospital. This facilitates learning on an individual and team level, while improving processes of patient care in a safe environment. In this quality improvement project themes were noted in simulation involving paediatric resuscitation, therefore targeted interventions were put in place to make improvements.ObjectivesIntervention One:Covid-19 has altered healthcare professionals approach to patient contact through the use of personal protective equipment (PPE) to ensure infection control. The Advanced Life Support Group endorsed guidance that in emergencies the patient should be assumed to have Covid-19 and full PPE should be used by responders. In paediatrics breathing support is essential;therefore unplanned simulation was run with staff to practice this skill while maintaining the safe use of PPE.Intervention Two:In simulated cardiac arrest the time taken to administer the first Adrenaline dose was over 13 minutes. Delays in administering Adrenaline in paediatric, in-hospital cardiac arrest with a non-shockable rhythm is associated with decreased survival, ROSC and survival with a favourable neurological outcome. ‘The Arrest to Adrenaline Race’ was launched with the aim to decrease the time taken to administer Adrenaline;so that in a real life scenario the patient would have the best chance of survival.MethodsIntervention One:In simulation it took 156 seconds until the patient was first bagged after responders correctly donned PPE, which would have a detrimental impact to successful resuscitation. ‘The Amber Bagging Race’ was launched where teams of healthcare professionals practiced the procedure in a race scenario;from recognition of a deteriorated patient, to the correct use of PPE and then successful bagging.Intervention Two:Healthcare professionals engaged in race scenarios with a manikin, where they timed the process taken from recognition of an arrested patient, initiating resuscitation, obtaining interosseous access and administering Adrenaline at the correct prescribed dose for weight.ResultsIntervention One:Over two weeks thirteen teams participated and the average time to bag was reduced to 56 seconds in week one and 41 seconds in week two. In a second unplanned paediatric resuscitation following ‘The Amber Bagging Race’ the time taken to bag the patient was 46 seconds;a significant improvement in clinical practice.Intervention Two:Over two weeks fourteen teams participated and the average time taken to administer Adrenaline reduced to 324 seconds in week one and 138 seconds in week two. In further simulation scenarios following ‘The Arrest to Adrenaline Race’ the time taken to administer Adrenaline averaged 5 minutes and 23 seconds.ConclusionsConclusion:Simulation identified key areas for improvement in paediatric resuscitation and targeted interventions enabled specific practice of skills, with the aim to improve patient care in a real life scenario. Learning was disseminated to the wider team and processes were altered to further improvements in patient safety. The races brought an atmosphere of fun to the ward, improving engagement and morale. People are often fearful of simulation;an environment of fun rather than fear is conducive to more effective learning.

SARS-CoV-2 infections among Australian passengers on the Diamond Princess cruise ship: A retrospective cohort study.

BACKGROUND: Prolonged periods of confined living on a cruise ship increase the risk for respiratory disease transmission. We describe the epidemiology and clinical characteristics of a SARS-CoV-2 outbreak in Australian passengers on the Diamond Princess cruise ship and provide recommendations to mitigate future cruise ship outbreaks. METHODS: We conducted a retrospective cohort study of Australian passengers who travelled on the Diamond Princess from 20 January until 4 February 2020 and were either hospitalised, remained in Japan or repatriated. The main outcome measures included an epidemic curve, demographics, symptoms, clinical and radiological signs, risk factors and length of time to clear infection. RESULTS: Among 223 Australian passengers, 56 were confirmed SARS-CoV-2 positive. Forty-nine cases had data available and of these over 70% had symptoms consistent with COVID-19. Of symptomatic cases, 17% showed signs and symptoms before the ship implemented quarantine and a further two-thirds had symptoms within one incubation period of quarantine commencing. Prior to ship-based quarantine, exposure to a close contact or cabin mate later confirmed SARS-CoV-2 positive was associated with a 3.78 fold (95% CI, 2.24-6.37) higher risk of COVID-19 acquisition compared to non-exposed passengers. Exposure to a positive cabin mate during the ship's quarantine carried a relative risk of 6.18 (95% CI, 1.96-19.46) of developing COVID-19. Persistently asymptomatic cases represented 29% of total cases. The median time to the first of two consecutive negative PCR-based SARS-CoV-2 assays was 13 days for asymptomatic cases and 19 days for symptomatic cases (p = 0.002). CONCLUSION: Ship based quarantine was effective at reducing transmission of SARS-CoV-2 amongst Australian passengers, but the risk of infection was higher if an individual shared a cabin or was a close contact of a confirmed case. Managing COVID-19 in cruise ship passengers is challenging and requires enhanced health measures and access to onshore quarantine and isolation facilities.