Electroconvulsive therapy in a tertiary Australian mental health facility between 2009 and 2020.

BACKGROUND: Despite electroconvulsive therapy being one of the most effective treatments in psychiatry, few studies report trends in the provision of electroconvulsive therapy over time. This study aims to investigate the use of electroconvulsive therapy between 2009 and 2020 in an Australian public tertiary mental health facility, and to describe the electroconvulsive therapy patient population and change in courses of treatment. METHODS: Routinely collected data for 677 patients who received 1669 electroconvulsive therapy courses of treatment at an Australian public tertiary mental health facility between 2009 and 2020 were examined. RESULTS: The provision of acute electroconvulsive therapy was stable across the study period; however, the number of maintenance electroconvulsive therapy courses commenced declined over the study. Schizophrenia was the most common indication for index treatment (37.4%). The majority of patients (85.7%) received acute electroconvulsive therapy only. Voluntary provision of electroconvulsive therapy declined over the study period, reducing from 44.9% in 2009 to 16.3% in 2020. CONCLUSION: Over the study period, there was a significant reduction in the number of maintenance electroconvulsive therapy courses commenced, and a large increase in involuntary treatment. The provision of electroconvulsive therapy was more likely to occur in males with a diagnosis of schizophrenia. Further studies are needed to generate a greater understanding of the factors influencing the provision of electroconvulsive therapy within differing geographical, social and healthcare landscapes.

The impact of the COVID-19 pandemic on antenatal care provision and associated mental health, obstetric and neonatal outcomes.

OBJECTIVES: The COVID-19 pandemic imposed many challenges on pregnant women, including rapid changes to antenatal care aimed at reducing the societal spread of the virus. This study aimed to assess how the pandemic affected perinatal mental health and other pregnancy and neonatal outcomes in a tertiary unit in Queensland, Australia. METHODS: This was a retrospective cohort study of pregnant women booked for care between March 2019 - June 2019 and March 2020 - June 2020. A total of 1984 women were included with no confirmed cases of COVID-19. The primary outcome of this study was adverse maternal mental health defined as an Edinburgh Postnatal Depression Scale score of ≥13 or an affirmative response to 'EPDS Question 10'. Secondary outcomes were preterm birth <37 weeks and <32 weeks, mode of birth, low birth weight, malpresentation in labour, hypertensive disease, anaemia, iron/vitamin B12 deficiency, stillbirth and a composite of neonatal morbidity and mortality. RESULTS: There were no differences in the primary perinatal mental health outcomes. The rates of composite adverse neonatal outcomes (27 vs. 34 %, p<0.001) during the pandemic were higher; however, there was no difference in perinatal mortality (p=1.0), preterm birth (p=0.44) or mode of delivery (p=0.38). CONCLUSIONS: Although there were no adverse consequences on maternal mental health during the pandemic, there was a concerning increase in neonatal morbidity potentially due to the altered model of maternity care implemented in the early COVID-19 pandemic.

Accuracy of intra-arterial line transducer levelling practice in a general intensive care unit.

BACKGROUND: The intra-arterial line is a common device intervention used in the intensive care environment to provide continuous blood pressure measurement. The transducer line is levelled to the patient's phlebostatic axis to provide accurate measurements. AIM: The aim of this study was to investigate registered nurses' accuracy at levelling the transducer to the correct anatomical position using visual judgement, compared to one done using a laser level. METHODS: Patient transducers were levelled by visual judgement and then by using a laser level. Time and mean arterial pressure (MAP) were recorded with each measurement along with any difference in transducer level between the two methods and subsequent changes in inotrope administration. RESULTS: A total of 577 MAP measurements were recorded from 178 patients; 70% of observations had a difference in transducer level, 30% of the time the inotrope rate was increased and 18% of the time the inotrope rate was reduced. The prevalence of clinically significant observations with an absolute difference of 50 mm or more in transducer placement was 25%. The mean difference in MAP measurements when a cut-off of 64 mmHg or more for laser was applied to the data was 0.22 (95% confidence interval: -0.14, 0.58, n = 513, p = 0.23), and for a cut-off of less than 64 for laser, a larger mean difference of 4.36 (95% confidence interval: 3.75, 5.28], n = 64, p < 0.001) was observed. CONCLUSIONS: Transducers were unable to be accurately levelled for haemodynamic monitoring using visual means alone. Over the range of patient MAP values examined, 25% of all observations had a clinically significant absolute difference of 50 mm or more in the transducer level position between the two methods. The visual method became increasingly inaccurate and unreliable at low MAP levels requiring medical intervention.

The impact of a cognitive impairment support program on patients in an acute care setting: a pre-test post-test intervention study.

BACKGROUND: Patients with cognitive impairment are at greater risk of hospital acquired complications, longer hospital stays, and poor health outcomes compared to patients without cognitive impairment. The Cognitive Impairment Support Program is a multi-disciplinary approach to improve screening rates and awareness of patients with cognitive impairment and guide clinician response and communication during their hospitalisation to improve health outcomes. OBJECTIVE: This study evaluated the impact of implementing the Cognitive Impairment Support Program on patient hospital acquired complications, patient reported quality of life and staff satisfaction in an outer metropolitan hospital. DESIGN: A pre-test post-test design was used to collect data in two 6-month time periods between March 2020 and November 2021. PARTICIPANTS: Patients aged ≥ 65 years, admitted to a participating ward for > 24 h. INTERVENTION: The Cognitive Impairment Support Program consisted of four components: cognitive impairment screening, initiation of a Cognitive Impairment Care Plan, use of a Cognitive Impairment Identifier and associated staff education. MEASURES: The primary outcome was hospital acquired complications experienced by patients with cognitive impairment identified using clinical coding data. Secondary outcomes were patient quality of life and a staff confidence and perceived organisational support to care for patients with cognitive impairment. RESULTS: Hospital acquired complication rates did not vary significantly between the two data collection periods for patients experiencing cognitive impairment with a 0.2% (95% confidence interval: -5.7-6.1%) reduction in admissions with at least one hospital acquired complication. Patients in the post intervention period demonstrated statistically significant improvements in many items in two of the Dementia Quality of Life Measure domains: memory and everyday life. The staff survey indicated statistically significant improvement in clinical staff confidence to care for patients with cognitive impairment (p = 0.003), satisfaction with organisational support for patients (p = 0.004) and job satisfaction (p ≤ 0.001). CONCLUSION: This study provides evidence that a multicomponent Cognitive Impairment Support Program had a positive impact on staff confidence and satisfaction and patient quality of life. Broader implementation with further evaluation of the multicomponent cognitive impairment intervention across a range of settings using varied patient outcomes is recommended.

A systematic review of the clinical impact of small colony variants in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a life-limiting disorder that is characterised by respiratory tract inflammation that is mediated by a range of microbial pathogens. Small colony variants (SCVs) of common respiratory pathogens are being increasingly recognised in CF. The aim of this systematic review is to investigate the prevalence of SCVs, clinical characteristics and health outcomes for patients with CF, and laboratory diagnostic features of SCVs compared to non-small colony variants (NCVs) for a range of Gram-positive and Gram-negative respiratory pathogens. METHODS: A literature search was conducted (PubMed, Web of Science, Embase and Scopus) in April 2020 to identify articles of interest. Data pertaining to demographic characteristics of participants, diagnostic criteria of SCVs, SCV prevalence and impact on lung function were extracted from included studies for analysis. RESULTS: Twenty-five of 673 studies were included in the systematic review. Individuals infected with SCVs of Staphylococcus aureus (S. aureus) were more likely to have had prior use of the broad-spectrum antibiotic trimethoprim sulfamethoxazole (p < 0.001), and the prevalence of SCVs in patients infected with S. aureus was estimated to be 19.3% (95% CI: 13.5% to 25.9%). Additionally, patients infected with SCVs of Gram-negative and Gram-positive pathogens were identified to have a lower forced expiratory volume in one second percentage predicted (-16.8, 95% CI: -23.2 to -10.4) than those infected by NCVs. Gram-positive SCVs were commonly described as small and non-haemolytic, grown on Mannitol salt or blood agar for 24 h at 35°C and confirmed using tube coagulase testing. CONCLUSION: The findings of this systematic review demonstrate that SCVs of S. aureus have a high prevalence in the CF community, and that the occurrence of SCVs in Gram-positive and Gram-negative pathogens is linked to poorer respiratory function. Further investigation is necessary to determine the effect of infection by SCVs on the CF population.

Can improvement in delivery of smoking cessation care be sustained in psychiatry inpatient settings through a system change intervention? An analysis of statewide administrative health data.

OBJECTIVE: This study evaluated maintenance of improved delivery of smoking cessation assistance in adult acute psychiatry inpatient units 3 years post statewide implementation of a system change intervention through analysis of a statewide administrative health dataset. METHOD: Rates of documenting smoking status and providing a brief smoking cessation intervention (the Smoking Cessation Clinical Pathway) in all eligible Queensland public adult acute psychiatry inpatient units (N = 57) during the implementation phase (October 2015-September 2017) of a system change intervention were compared to the maintenance phase (October 2017-October 2020) using interrupted time series analysis. RESULTS: Across implementation and maintenance phases, the percentage of discharges from psychiatry inpatient units that had a smoking status recorded remained high with the statewide average exceeding 90% (implementation phase 93.2%, 95% confidence interval = [92.4, 93.9]; and maintenance phase 94.6%, 95% confidence interval = [94.0, 95.2]). The percentage of discharges statewide with a completed Pathway stabilised during the maintenance phase (change in slope -3.7%, 95% confidence interval = [-5.2, -2.3]; change in level 0.4%, 95% confidence interval = [-7.0, 7.9]). CONCLUSION: An evidence-based smoking cessation intervention implemented with a system change intervention resulted in sustained improvement in addressing smoking in adult inpatient psychiatry units up to 3 years post implementation.

'Propped and prone' positioning reduces respiratory events in spontaneously breathing preterm infants: A randomised triple crossover study.

AIM: We compared effects of infant positioning and feed-rate interventions on respiratory events and oximetry parameters in spontaneously breathing preterm infants born <32 weeks gestation managed in a neonatal unit. METHODS: A randomised triple crossover design was employed. n = 68 infants underwent three test conditions A: control (supine/flat, gravity bolus feeds), B: position intervention (propped/prone) and C: feed-rate intervention (continuous pump feeds) in randomised sequence over three consecutive days. Primary outcomes were number of events (apnoea, bradycardia and desaturation) and percentage time SpO2 < 80% over 24 h. The secondary outcome was percentage time SpO2 ≥ 88%. Treatment effects were estimated using linear mixed-effects models. RESULTS: Propped/prone positioning significantly reduced events and improved percentage time SpO2 < 80% and ≥88% compared to both other conditions (all P < 0.001). Outcomes for the feed-rate intervention were not significantly different to control. CONCLUSIONS: Alternative infant positioning should be considered in preterm infants managed in the neonatal unit.

Fathers attending the birth of their baby: Views, intentions and needs.

BACKGROUND: There is limited information about fathers' views, intentions and needs leading up to childbirth. AIMS: This study explores the factors influencing fathers' intention to attend the birth, and the needs and supports required leading up to childbirth. METHODS: Cross-sectional survey of 203 prospective fathers attending antenatal appointments at an outer metropolitan public teaching hospital in Brisbane, Australia. RESULTS: A total of 201/203 (99.0%) participants intended to attend the birth. The reported reasons included: responsibility (99.5%), protectiveness (99.0%), love for their partner (99.0%), the right thing to do (98.0%), desire to see the birth (98.0%), the perception that partners should attend (97.4%), duty (96.4%) and partner preference (91.4%). Some felt pressured by their partner (12.8%), society (10.8%), cultural expectations (9.6%) and family (9.1%), and 10.6% perceived adverse consequences for not attending. Most participants (94.6%) felt well supported, experienced good communication (72.4%), had the opportunity to ask questions (69.8%) and received an explanation of events (66.3%). They were less often supported by antenatal visits (46.7%) and by a plan for future visits (32.2%). Ten per cent of all fathers and 13.8% of experienced fathers requested better mental health support, and 9.0% prefer better clinician communication. CONCLUSIONS: Most fathers intend to attend childbirth for personal and moral reasons; however, a small proportion feel pressured. Most fathers feel well supported, although potential improvements include planning for future visits, provision of information, mental health support, clinician communication, increased involvement in their partner's care, the opportunity to ask questions and more frequent clinic visits.

Antimalarial Activity of Artefenomel Against Asexual Parasites and Transmissible Gametocytes During Experimental Blood-Stage Plasmodium vivax Infection.

BACKGROUND: Interventions that effectively target Plasmodium vivax are critical for the future control and elimination of malaria. We conducted a P. vivax volunteer infection study to characterize the antimalarial activity of artefenomel, a new drug candidate. METHODS: Eight healthy, malaria-naive participants were intravenously inoculated with blood-stage P. vivax and subsequently received a single oral 200-mg dose of artefenomel. Blood samples were collected to monitor the development and clearance of parasitemia, and plasma artefenomel concentration. Mosquito feeding assays were conducted before artefenomel dosing to investigate parasite transmissibility. RESULTS: Initial parasite clearance occurred in all participants after artefenomel administration (log10 parasite reduction ratio over 48 hours, 1.67; parasite clearance half-life, 8.67 hours). Recrudescence occurred in 7 participants 11-14 days after dosing. A minimum inhibitory concentration of 0.62 ng/mL and minimum parasiticidal concentration that achieves 90% of maximum effect of 0.83 ng/mL were estimated, and a single 300-mg dose was predicted to clear 109 parasites per milliliter with 95% certainty. Gametocytemia developed in all participants and was cleared 4-8 days after dosing. At peak gametocytemia, 75% of participants were infectious to mosquitoes. CONCLUSIONS: The in vivo antimalarial activity of artefenomel supports its further clinical development as a treatment for P. vivax malaria. CLINICAL TRIALS REGISTRATION: NCT02573857.

When is it too late? Ovarian preservation and duration of symptoms in ovarian torsion.

This 10-year retrospective study between 2008 and 2018, aims to investigate the duration of symptoms of ovarian torsion and the subsequent rate of ovarian preservation. Eighty-six women with surgically confirmed ovarian torsion were included. The median duration from the onset of pain symptoms to presentation (26.0 vs 6.0 h, p < .001) and from presentation to surgery (11.0 vs 5.5 h, p = .010) were significantly longer in women who required an oophorectomy compared to women who had conservative surgery. There was no significant difference in symptoms, signs or investigations except ultrasound finding of an enlarged ovary (94.9% vs 76.9%, p = .026). Awareness of the condition among the community and healthcare is crucial and routine investigations should not delay management as positive Doppler flow on ultrasound does not exclude an ovarian torsion.Impact StatementWhat is already known on this subject? Ovarian torsion is a gynaecological emergency and may lead to ovarian necrosis, infection and peritonitis. Early recognition is essential in preserving the ovary, particularly in patients with future fertility aspirations. Currently there is no consensus regarding the time period of ovarian viability after the onset of symptoms.What do the results of this study add? We have demonstrated a significant difference in the duration from the onset of symptoms to surgery. Furthermore, the duration from the onset of symptoms to presentation (26.0 vs 6.0 h, p<.001) and from presentation to surgery (11.0 vs 5.5 h, p=.010) were significantly longer in women who required an oophorectomy compared to women who had conservative surgery. There was no significant difference in symptoms, signs or investigations except ultrasound finding of an enlarged ovary.What are the implications of these findings for clinical practice and/or further research? Women with known ovarian cysts in particular should be educated of the risk of ovarian torsion. Routine investigations should not delay management as it does not exclude an ovarian torsion. Although our study suggests that early presentation and management would reduce the risk of oophorectomy, prospective studies are required to confirm the findings.

Analytical validation of a real-time hydrolysis probe PCR assay for quantifying Plasmodium falciparum parasites in experimentally infected human adults.

BACKGROUND: Volunteer infection studies have become a standard model for evaluating drug efficacy against Plasmodium infections. Molecular techniques such as qPCR are used in these studies due to their ability to provide robust and accurate estimates of parasitaemia at increased sensitivity compared to microscopy. The validity and reliability of assays need to be ensured when used to evaluate the efficacy of candidate drugs in clinical trials. METHODS: A previously described 18S rRNA gene qPCR assay for quantifying Plasmodium falciparum in blood samples was evaluated. Assay performance characteristics including analytical sensitivity, reportable range, precision, accuracy and specificity were assessed using experimental data and data compiled from phase 1 volunteer infection studies conducted between 2013 and 2019. Guidelines for validation of laboratory-developed molecular assays were followed. RESULTS: The reportable range was 1.50 to 6.50 log10 parasites/mL with a limit of detection of 2.045 log10 parasites/mL of whole blood based on a parasite diluted standard series over this range. The assay was highly reproducible with minimal intra-assay (SD = 0.456 quantification cycle (Cq) units [0.137 log10 parasites/mL] over 21 replicates) and inter-assay (SD = 0.604 Cq units [0.182 log10 parasites/mL] over 786 qPCR runs) variability. Through an external quality assurance program, the QIMR assay was shown to generate accurate results (quantitative bias + 0.019 log10 parasites/mL against nominal values). Specificity was 100% after assessing 164 parasite-free human blood samples. CONCLUSIONS: The 18S rRNA gene qPCR assay is specific and highly reproducible and can provide reliable and accurate parasite quantification. The assay is considered fit for use in evaluating drug efficacy in malaria clinical trials.

Hypophosphatemia and Outcomes in ICU: A Systematic Review and Meta-Analysis.

PURPOSE: Hypophosphatemia is reported in up to 5% of hospitalized patients and ranges from 20% to 80% in critically ill patients. The consequences of hypophosphatemia for critically ill patients remain controversial. We evaluated the effect of hypophosphatemia on mortality and length of stay in intensive care unit (ICU) patients. METHODS: MEDLINE, EMBASE, Cochrane Library (Reviews and Trials), and PubMed were searched for articles in English. The primary outcome was mortality and secondary outcome was length of stay. The quality of evidence was graded using a modified Newcastle-Ottawa Scale. RESULTS: Our search yielded 828 articles and ultimately included 12 studies with 7626 participants in the analysis. Hypophosphatemia was associated with increased hospital length of stay (2.19 days [95% CI, 1.74-2.64]) and ICU length of stay (2.22 days [95% CI, 1.00-3.44]) but not mortality (risk ratio: 1.13 [95% CI, 0.98-1.31]; P = .09). CONCLUSIONS: Hypophosphatemia in ICU was associated with increased hospital and ICU length of stay but not all-cause mortality. Hypophosphatemia appears to be a marker of disease severity. Limited number of available studies and varied study designs did not allow for the ascertainment of the effect of severe hypophosphatemia on patient mortality.

Impact of early surgical management on tubo-ovarian abscesses.

This 5-year retrospective study aimed to investigate whether early surgical management improves outcomes in patients presenting with a tubo-ovarian abscess (TOA). Patient characteristics, investigation results and treatment outcomes were compared. 50 women were diagnosed with a TOA during the study period. Nineteen (38.0%) were treated with antibiotics (medical group) and thirty one (62.0%) were treated surgically on admission (early surgical group). The early surgical group was associated with a high success rate of 96.8% and the lowest risk of readmission within 12 months (16.1%). There was no significant difference in the length of stay between the early surgical and the successful medical group.Impact StatementWhat is already known on this subject? Tubo-ovarian abscess (TOA) is an inflammatory mass that forms most commonly as a complication of untreated pelvic inflammatory disease (PID). Traditionally, TOAs are treated first with broad-spectrum intra-venous antibiotics, with surgical intervention considered after 72 h. It is not known whether early surgical intervention would be beneficial to patient outcomes compared to traditional management.What do the results of this study add? In this study, we have demonstrated a high success rate with early surgical management. Readmission rate was lowest in the early surgical group compared to the medical and late surgical group. This suggests that early surgical intervention may be beneficial, compared to the standard management of trialling antibiotics and then proceeding to surgery 72 h later.What are the implications of these findings for clinical practice and/or further research? Our study suggests that early surgery may be beneficial in the management of TOAs. Although we were unable to demonstrate statistical significance, our data suggest that it would be worthwhile to investigate white blood cell (WBC) and C-reactive protein (CRP) further as a potential predictor for failure of medical management. In the future, more studies comparing early surgical management with medical and late surgical management could inform clinicians of the best mode of treatment for these patients.

Assays for quantification of male and female gametocytes in human blood by qRT-PCR in the absence of pure sex-specific gametocyte standards.

BACKGROUND: Malaria transmission from humans to Anopheles mosquitoes requires the presence of gametocytes in human peripheral circulation, and the dynamics of transmission are determined largely by the density and sex ratio of the gametocytes. Molecular methods are thus employed to measure gametocyte densities, particularly when assessing transmission epidemiology and the efficacy of transmission-blocking interventions. However, accurate quantification of male and female gametocytes with molecular methods requires pure male and female gametocytes as reference standards, which are not widely available. METHODS: qRT-PCR assays were used to quantify levels of sex-specific mRNA transcripts in Plasmodium falciparum female and male gametocytes (pfs25 and pfMGET, respectively) using synthetic complimentary RNA standards and in vitro cultured gametocytes. Assays were validated and assay performance was investigated in blood samples of clinical trial participants using these standards and compared to absolute quantification by droplet digital PCR (ddPCR). RESULTS: The number of transcript copies per gametocyte were determined to be 279.3 (95% CI 253.5-307.6) for the female-specific transcript pfs25, and 12.5 (95% CI 10.6-14.9) for the male-specific transcript pfMGET. These numbers can be used to convert from transcript copies/mL to gametocyte/mL. The reportable range was determined to be 5.71 × 106 to 5.71 female gametocytes/mL for pfs25, and 1.73 × 107 to 1.73 × 101 male gametocytes/mL for pfMGET. The limit of detection was 3.9 (95% CI 2.5-8.2) female gametocytes/mL for pfs25, and 26.9 (95% CI 19.3-51.7) male gametocytes/mL for PfMGET. Both assays showed minimal intra-assay and inter-assay variability with coefficient of variation < 3%. No cross-reactivity was observed in both assays in uninfected human blood samples. Comparison of results from ddPCR to qRT-PCR assays on clinical blood samples indicated a high-level agreement (ICC = 0.998 for pfs25 and 0.995 for pfMGET). CONCLUSIONS: This study reports the validation of qRT-PCR assays that are able to accurately quantify female and male P. falciparum gametocytes at sub-microscopic densities. The assays showed excellent reproducibility, sensitivity, precision, specificity, and accuracy. The methodology will enable the estimation of gametocyte density in the absence of pure female and male gametocyte standards, and will facilitate clinical trials and epidemiological studies.

A randomized controlled trial of daily weighing in pregnancy to control gestational weight gain.

BACKGROUND: Excessive gestational weight gain is a modifiable risk factor for the development of obstetric and neonatal complications, and can have a lifelong impact on the health of both mother and offspring. The purpose of this study was to assess whether in addition to standardized medical advice regarding weight gain in pregnancy (including adherence to the Institute of Medicine (IOM) guidelines) (IOM (Institute of Medicine) and NRC (National Research Council, Weight Gain During Pregnancy: Re-examining the guidelines, 2009)), the addition of daily weighing would provide a low cost and simple intervention to reduce excessive weight gain in pregnancy by maintaining weight gain within the target range. METHODS: Women presenting for antenatal care to a secondary level hospital were randomised to routine care or daily weight monitoring. Both groups received nutrition and exercise advice. RESULTS: Three hundred and ninety-six women were randomised to either the daily weight monitoring group or control group with complete data available for 326 women. The percentage weight gain above target (86.9% (SD 52.3) v 92.7% (SD 50.8) p = 0.31) and change in weight per week during the study period (0.59 kg (SD 0.30) v 0.63 kg (SD 0.31) p = 0.22) were lesser in those undergoing daily weighing compared to routine management, however these did not reach statistical significance. CONCLUSION: Daily weight monitoring as a stand-alone intervention has potential to reduce excessive gestational weight gain. It may have a role as a part of a larger intervention involving dietary and exercise modifications. TRIAL REGISTRATION: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry. (ACTRN12613001165774, 23/10/ 2013).

Centralised versus outreach models of cystic fibrosis care should be tailored to the needs of the individual patient.

Cystic fibrosis (CF) is a common life-limiting genetic condition. As the disease progresses access to specialist tertiary multi-disciplinary care services may become necessary. For patients living in regional/remote Australia, accessing such services may be a challenge. Here, we describe long-term outcomes for CF patients according to their access to specialist CF centre care in childhood.

Current infection control practices used in Australian and New Zealand cystic fibrosis centers.

BACKGROUND: The 2013 update of the Infection Prevention and Control (IP&C) Guideline outlined recommendations to prevent the spread of CF respiratory pathogens. We aimed to investigate the current infection control practices used in Australian and New Zealand (NZ) CF centers. METHODS: Two online surveys were distributed to Australian and NZ CF centers regarding the uptake of selected IP&C recommendations. One survey was distributed to all the Medical Directors and Lead CF Nurses and the second survey was distributed to all the Lead CF Physiotherapists. RESULTS: The response rate was 60% (60/100) for medical/nursing and 58% (14/24) for physiotherapy. Over 90% (55/60) of CF centers followed CF-specific infection control guidelines and consistent infection control practices were seen in most CF centers; 76% (41/54) had implemented segregation strategies for ambulatory care and no CF centers housed people with CF in shared inpatient accommodation. However, the application of contact precautions (wearing gloves and apron/gown) by healthcare professionals when reviewing a CF person was variable between CF center respondents but was most often used when seeing CF persons with MRSA infection in both ambulatory care and hospital admission (20/50, 40% and 42/45, 93% of CF centers, respectively). Mask wearing by people with CF was implemented into 61% (36/59) of centers. Hospital rooms were cleaned daily in 79% (37/47) of CF centers and the ambulatory care consult rooms were always cleaned between consults (49/49, 100%) and at the end of the clinic session (51/51, 100%); however the staff member tasked with cleaning changed with 37% (18/49) of CF centers responding that CF multidisciplinary team (MDT) members cleaned between patients whereas at the end of the clinic session, only 12% (6/51) of the CF MDT cleaned the consult room. CONCLUSIONS: Overall, Australian and NZ CF centers have adopted many recommendations from the IP&C. Although, the application of contact precautions was inconsistent and had overall a low level of adoption in CF centers. In ~ 25% of centers, mixed waiting areas occurred in the ambulatory care. Given the variability of responses, additional work is required to achieve greater consistency between centers.

The impact of removing gastric residual volume monitoring and enteral nutrition rate titration in adults receiving mechanical ventilation.

BACKGROUND: Monitoring gastric residual volume (GRV) and titrating enteral nutrition (EN) towards goal rate are common practices in the intensive care unit (ICU) despite limited supportive evidence. We investigated the effect of removal of GRV monitoring and commencing EN at goal rate had on EN provision in mechanically ventilated ICU patients. METHODS: We conducted a single-centre, pre-post implementation study, in a 10-bed ICU comprising 181 patients with ventilation ≥48 h and given EN within 24 h of intubation. EN adequacy, expressed as the proportion of patients receiving ≥90% of the prescribed volume during the first 24 h of feeding, was compared before and after implementation. Secondary outcomes included EN adequacy over entire ICU stay; incidence of gastrointestinal intolerance in terms of vomiting, abdominal distension, and GRV >200 ml; prokinetic use; onset of a ventilator-associated condition; ventilation duration; length of stay; and mortality. RESULTS: After intervention, the proportion of patients meeting ≥90% of their prescribed EN volume within the first 24 h of feeding increased by 38.1% (pre: 46.4%, 95% confidence interval [CI]: 36.7-56.3; post: 84.5%, 95% CI: 75.8-91.2; p < 0.001). Over their entire ICU stay, the proportion of patients meeting ≥90% of their prescribed EN volume increased by 21.4% (pre: 61.9%, 95% CI: 52.0-71.1; post: 83.3%, 95% CI: 74.4-90.2; p = 0.001). Gastrointestinal intolerance reduced by 34.0% (pre: 80.4%, 95% CI: 71.8-87.5; post: 46.4%, 95% CI: 36.0-57.1; p < 0.001) and fewer prescribed prokinetic agents (pre: 57.7%, 95% CI: 47.8-67.3; post: 23.8%, 95% CI: 15.6-33.6; p < 0.001). CONCLUSIONS: Removal of GRV monitoring and commencing EN at goal resulted in significantly increased EN provision during the first 24 h of feeding and entire ICU stay with reduced prokinetic use and gastrointestinal complications.

DSM265 at 400 Milligrams Clears Asexual Stage Parasites but Not Mature Gametocytes from the Blood of Healthy Subjects Experimentally Infected with Plasmodium falciparum.

DSM265 is a novel antimalarial drug in clinical development that acts as a selective inhibitor of Plasmodium dihydroorotate dehydrogenase. In a previous phase 1b study, a single 150-mg dose of DSM265 showed partial efficacy against experimentally induced blood-stage Plasmodium falciparum malaria (IBSM). Pharmacokinetic/pharmacodynamic modeling predicted a human efficacious dose of 340 mg. The primary objectives of the current study were to determine the safety and efficacy of a single oral 400-mg dose of DSM265 against P. falciparum in the IBSM model. Eight healthy participants were inoculated intravenously with 2,800 parasites and treated with DSM265 7 days later. Unexpectedly, one participant did not develop parasitemia during the study. All other participants developed parasitemia, with the complete clearance of asexual parasites occurring following DSM265 treatment. All seven subjects also became gametocytemic. The secondary objectives were to investigate the gametocytocidal and transmission-blocking activity of a second 400-mg dose of DSM265, which was administered 23 days after inoculation. Gametocytes were not cleared by the second dose of DSM265, and transmission-blocking activity could not be determined due to low gametocyte densities. Three DSM265-related adverse events occurred, including a cutaneous rash in one subject on the day of the second DSM265 dose. The results obtained in this study support the prediction of the efficacious dose of DSM265 and provide further evidence that DSM265 is generally safe and well tolerated. In addition, this study confirms preclinical data indicating that DSM265 permits the development and maturation of gametocytes and does not clear mature circulating gametocytes. (This study has been registered at ClinicalTrials.gov under identifier NCT02573857.).

A Single-Dose Combination Study with the Experimental Antimalarials Artefenomel and DSM265 To Determine Safety and Antimalarial Activity against Blood-Stage Plasmodium falciparum in Healthy Volunteers.

Artefenomel and DSM265 are two new compounds that have been shown to be well tolerated and effective when administered as monotherapy malaria treatment. This study aimed to determine the safety, pharmacokinetics, and pharmacodynamics of artefenomel and DSM265 administered in combination to healthy subjects in a volunteer infection study using the Plasmodium falciparum-induced blood-stage malaria model. Thirteen subjects were inoculated with parasite-infected erythrocytes on day 0 and received a single oral dose of artefenomel and DSM265 on day 7. Cohort 1 (n = 8) received 200 mg artefenomel plus 100 mg DSM265, and cohort 2 (n = 5) received 200 mg artefenomel plus 50 mg DSM265. Blood samples were collected to measure parasitemia, gametocytemia, and artefenomel-DSM265 plasma concentrations. There were no treatment-related adverse events. The pharmacokinetic profiles of artefenomel and DSM265 were similar to those of the compounds when administered as monotherapy, suggesting no pharmacokinetic interactions. A reduction in parasitemia occurred in all subjects following treatment (log10 parasite reduction ratios over 48 h [PRR48] of 2.80 for cohort 1 and 2.71 for cohort 2; parasite clearance half-lives of 5.17 h for cohort 1 and 5.33 h for cohort 2). Recrudescence occurred in 5/8 subjects in cohort 1 between days 19 and 28 and in 5/5 subjects in cohort 2 between days 15 and 22. Low-level gametocytemia (1 to 330 female gametocytes/ml) was detected in all subjects from day 14. The results of this single-dosing combination study support the further clinical development of the use of artefenomel and DSM265 in combination as a treatment for falciparum malaria. (This study has been registered at ClinicalTrials.gov under identifier NCT02389348.).