Evaluating appropriateness of 18F-fluciclovine PET/CT relative to standard of care imaging guidelines and the impact of ADT on positivity: a prospective study in 62 Veterans Administration patients at a single institution.

BACKGROUND: According to the National Comprehensive Cancer Network Guidelines, 18F-fluciclovine PET/CT is considered appropriate after negative standard of care (SOC) imaging. OBJECTIVE: To prospectively compare 18F-fluciclovine to SOC imaging, investigate whether it should be done when SOC imaging is (+), and evaluate its detection rate in patients receiving androgen deprivation therapy. METHODS: We recruited 57 prostate cancer patients with biochemical recurrence with 18F-fluciclovine PET/CT and SOC imaging within 30 days. Prostate-specific antigen (PSA) level, Gleason score (GS), history of radical prostatectomy (RP), radiation therapy (RT) or hormone therapy (HT) were reviewed. RESULTS: The 57 patients had a median PSA of 2.6 and average GS of 7.4; 27 (47.4%) had RP, 28 (49.1%) had RT, 1 (1.75%) had HT and 1 (1.75%) observation only. 18F-fluciclovine identified disease recurrence in 45/57 patients (78.9%), including oligometastasis in 18/45 (40%). SOC imaging identified recurrent disease in 12/57 patients (21.1%) while 18F-fluciclvoine identified additional sites of disease in 11/12 (91.7%). The (+) 18F-fluciclovine studies had a median PSA 2.6 ng/ml compared to 6.0 ng/ml in the (+) SOC studies. CONCLUSION: 18F-fluciclovine was superior to SOC imaging for lesion detection, identification of oligometastasis and identification of additional sites of disease.

Australian National Standards of Care for Childhood-onset Heart Disease (CoHD Standards). 1st Edition.

These first Australian National Standards of Care for Childhood-onset Heart Disease (CoHD Standards) have been developed to inform the healthcare requirements for CoHD services and enable all Australian patients, families and carers impacted by CoHD (paediatric CoHD and adult congenital heart disease [ACHD]) to live their best and healthiest lives. The CoHD Standards are designed to provide the clarity and certainty required for healthcare services to deliver excellent, comprehensive, inclusive, and equitable CoHD care across Australia for patients, families and carers, and offer an iterative roadmap to the future of these services. The CoHD Standards provide a framework for excellent CoHD care, encompassing key requirements and expectations for whole-of-life, holistic and connected healthcare service delivery. The CoHD Standards should be implemented in health services in conjunction with the National Safety and Quality Health Service Standards developed by the Australian Commission on Safety and Quality in Health Care. All healthcare services should comply with the CoHD Standards, as well as working to their organisation's or jurisdiction's agreed clinical governance framework, to guide the implementation of structures and processes that support safe care.

Nutrition supplementation plus standard of care versus standard of care alone or standard of care plus unconditional cash transfer in the prevention of chronic malnutrition in Southern Angola: study protocol for the MuCCUA study, a cluster randomized controlled trial.

BACKGROUND: Chronic malnutrition is a condition associated with negative impacts on physical and cognitive development. It is multi-causal and can start very early in life, already in utero, thus it is especially challenging to find appropriate interventions to tackle it. The government of Angola is implementing a standard of care program with potential to prevent it, and the provision of cash transfers and the supplementation with small quantity lipid-based nutrients (SQ-LNS) are also promising interventions. We aimed to evaluate the impact of the standard of care program alone and of the standard of care plus a cash transfer intervention in the lineal growth of children less than 2 years old and compare it to the effectiveness of a nutrition supplementation plus standard of care program in Southern Angola. METHODS/DESIGN: The three-arm parallel cluster randomised controlled trial is set in four communes of Huila and Cunene provinces. Clusters are villages or neighbourhoods with a population around 1075 people. A total of twelve clusters were selected per arm and forty pregnant women are expected to be recruited in each cluster. Pregnant women receive the standard of care alone, or the standard of care plus unconditional cash transfer or plus nutritional supplementation during the first 1000 days, from pregnancy to the child reaching 24 months. The primary outcome is the prevalence of stunting measured as height-for-age Z-score (HAZ) < -2 in children below 2 years. Impact will be assessed at 3, 6, 12, 18 and 24 months of children's age. Secondary outcomes include mortality, morbidity, caring, hygiene and nutrition behaviours and practices, and women and children's dietary diversity. Quantitative data are also collected on women's empowerment, household food security, expenditure and relevant clinical and social events at baseline, endline and intermediate time points. DISCUSSION: The results will provide valuable information on the impact of the standard of care intervention alone as well as combined with an unconditional cash transfer intervention compared to a nutrition supplementation plus standard of care intervention, carried out during the first 1000 days, in the children´s growth up to 2 years and related outcomes in Southern Angola. TRIAL REGISTRATION: Clinical Trials NCT05571280. Registered 7 October 2022.

International standards of care in thoracic oncology: A narrative review of clinical quality indicators.

Unwarranted variations in lung cancer care are widely described. Clinical Quality Indicators (CQIs) enable the systematic identification and alleviation of variations in care and other evidence-practice gaps. The aim of this review was to describe and evaluate lung cancer CQIs utilised internationally, in order to provide a substrate for the development of Australasian lung cancer CQIs and future quality improvement initiatives. A literature search was performed to identify relevant publications; references were excluded if they did not explicitly define original lung cancer-specific quality indicators, or were review or opinion articles. Ultimately, 48 publications containing 661 individual CQIs were evaluated. Although almost all references were published in the last decade, CQIs did not always reflect contemporary standards of care. For example, there were just sixteen CQIs regarding biomarker profiling, eleven CQIs regarding multidisciplinary team review, and three clinical trial enrolment CQIs. Of 307 lung cancer treatment CQIs, almost half (137) pertain to surgical resection; a treatment option available to a minority of lung cancer patients. Consumer engagement during indicator development was uncommon. In conclusion, whilst CQIs are widely measured and reported, they are not always consistent with evidence-based practice, nor do they reliably support the holistic evaluation of the lung cancer care continuum. Moving forward, Australia and New Zealand must adopt a unified, evidence-based and patient-centred approach to drive meaningful improvements in practice.

Co-administration of AYUSH 64 as an adjunct to standard of care in mild and moderate COVID-19: A randomized, controlled, multicentric clinical trial.

OBJECTIVE: Evaluate the efficacy of AYUSH 64, a standard polyherbal Ayurvedic drug in COVID-19. METHODS: During the first pandemic wave, 140 consenting and eligible hospitalized adult participants with mild-moderate symptomatic disease (specific standard RT-PCR assay positive) were selected as per a convenience sample, and randomized (1:1 ratio) to an open-label (assessor blind) two-arm multicentric drug trial; standard of care (SOC as per Indian guidelines) versus AYUSH 64 combined with SOC (AYUSH plus). Participants were assessed daily and discharged once clinical recovery (CR, primary efficacy) was achieved which was based on a predetermined set of criteria (resolution of symptoms, normal peripheral oximetry, and negative specific RT-PCR assay). Each participant was followed using an indigenous software program(mobile phone) and completed a 12-week study period. The dose of AYUSH 64 was 2 tablets oral, 500 mg each, bid for 12 weeks (AYUSH plus only). Significant P was <0.05 (two-sided). On randomization, the groups were found well matched. RESULTS: The mean interval time from randomization to CR was significantly superior in the AYUSH plus group [mean 6.45 days versus 8.26 days, 95% Confidence Interval of the difference -3.02 to -0.59 (P = 0.003, Student's 't test] as per-protocol analysis (134 participants); significant (P = 0.002) on an intention to treat analysis. 70% of the participants in AYUSH plus recovered during the first week (P = 0.046, Chi-square) and showed a significantly better change in physical health, fatigue, and quality of life measures. 48 adverse events, mostly mild and gut related, were reported by each group. There were 20 patient withdrawals (8 in AYUSH plus) but none due to an AE. There were no deaths. Daily assessment (hospitalization) and supervised drug intake ensured robust efficacy data. The open-label design was a concern (study outcome). CONCLUSIONS: AYUSH 64 in combination with SOC hastened recovery, reduced hospitalization, and improved health in COVID-19. It was considered safe and well-tolerated. Further clinical validation (Phase III) is required. TRIAL REGISTRATION: CTRI/2020/06/025557.

World professional association for transgender health guidelines: 2022 surgical treatment updates in the standards of care for transgender and gender diverse people.

INTRODUCTION: The World Professional Association for Transgender Health has recently updated its Standards of Care (SOC) clinical guidelines for the transgender and gender diverse (TGD) population. This article aims to outline the 2012 SOC for surgical management of TGD people and describe the changes to the surgical management guidelines in this year's update. METHODS AND RESULTS: The surgical management guidelines between the 7th and 8th SOC were compared and contrasted. The 8th SCO included language that broadened surgical interventions and emphasized the new responsibilities of surgeons. Major changes include reducing the number of letters of referral by a mental health provider to one for those choosing to undergo surgical treatment. CONCLUSIONS: The latest surgical management guidelines for the TGD population emphasizes a holistic approach utilizing a multidisciplinary team in both pre- and postoperative settings.

Cost-effectiveness analysis of grass pollen specific immunotherapy in children with allergic rhinitis compared to the standard of care symptomatic treatment in Portugal.

Summary: Background. Cost-effectiveness studies evaluating allergen immunotherapy (AIT) in children are scarce. We aim to compare the cost-effectiveness of subcutaneous (SCIT) and sublingual immunotherapy (SLIT) against standard-of-care (SOC) treatment in children with grass pollen allergic rhinitis. Methods. We created a Markov model to compare the three strategies over a 10-year horizon. SOC was the reference to calculate the incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analysis were used to assess models' uncertainty. Results. We obtained an ICER of € 12,605 and € 6,318 for SLIT and SCIT, respectively. In sensitivity analysis, SCIT was more cost-effective than SLIT. Conclusions. AIT is cost-effective in children with grass pollen allergic rhinitis, especially for the subcutaneous route.

Efficacy of Dashmool Vasti as an adjuvant therapy with the standard of care (modern + physiotherapy) in the rehabilitation of stroke as compared to standard of care - a clinical trial protocol.

Background: Stroke is ischemia and neurological dysfunction caused by acute brain circulation loss. It causes acute localized neurological abnormalities such as weakness, sensory deficit, or language issues that require long-term treatment. These deficiencies harm the patient and their family psychologically, socially, and economically. Thus, combination treatment can rapidly rehabilitate such patients. Detoxification methods like Ayurvedic medicated enema help stroke pathophysiology. Physical modalities in physiotherapy have been shown to facilitate normal movement and function on the stroke patient's affected side, increasing independence with everyday duties. A stroke patient may benefit from Dashmoola Niruha Basti, Function Electrical Stimulation (FES), and Motor Relearning Programme (MRP). Aim & Objectives: This study compares the adjuvant role of Dashmoola Basti with MRP and FES in stroke recovery. The main goals of this study are to assess and compare the adjuvant role of Dashmoola Basti with standard control over sensorimotor function of lower extremities, static and dynamic balance in stroke patients; gait parameters; resistance experienced during passive range of motion; quality of life of patients; Barthel Index; Modified Ashworth Scale; and Fuglmeyer assessment, Single Limb Stance Test, Functional Reach Test. Methods: A total of 40 patients will be enrolled and divided randomly into two equal groups. In Group A (control), standard treatment (modern + physiotherapy) will be prescribed for one month. In Group B (interventional group), Dashmoola Basti will be added to the aforementioned standard treatment for one month. Expected results: Improvement in Fuglmeyer assessment, Single Limb Stance Test, Functional Reach Test, quality of Life of Patients, Barthel Index, Modified Ashworth scale, and National Institute of Health (NIH) stroke-scale-score will be observed and recorded. Conclusions: Results and conclusions will be derived according to the data collected in case record form and assessment sheets filled at baseline and follow-up visits. Trial registration: CTRI/2021/10/037445 dated 21.10.2021.

The theoretical and practical arguments against the unilateral withdrawal of life-sustaining treatment during crisis standards of care: Does the Knobe effect apply to unilateral withdrawal?

Some argue that it is ethically justifiable to unilaterally withdraw life-sustaining treatment during crisis standards of care without the patient's consent in order to reallocate it to another patient with a better chance of survival. This justification has been supported by two lines of argument: the equivalence thesis and the rule of the double effect. We argue that there are theoretical issues with the first and practical ones with the second, as supported by an experiment aimed at exploring whether the Knobe effect, which affects the folk concept of intention, applies to situations of unilateral withdrawal. Fifty-two critical care physicians from one university were asked to ascribe intention in two hypothetical scenarios A and B in which outcomes differ-the patient from whom life-sustaining treatment is withdrawn dies in scenario A but survives in scenario B-but the intention, to save the other patient regardless of the outcome of the other, is the same. The survey was administered via a web-based survey and all answers were anonymous. A paired proportion test was used to compare responses to both questions. All 52 surveyed individuals responded in scenario A and 30 (57.7%) ascribed intention when outcomes were unfavorable, whereas 50 responded in scenario B and 8 (16%) ascribed intention when outcomes were favorable, a difference that was statistically significant (p < 0.001). There are theoretical and practical issues with the arguments proposed to justify the unilateral withdrawal of life-sustaining treatment based on the equivalence thesis and the rule of double effect.

Is short-course radiotherapy and total neoadjuvant therapy the new standard of care in locally advanced rectal cancer? A sensitivity analysis of the RAPIDO clinical trial.

BACKGROUND: The results of the RAPIDO trial have been accepted as evidence in favour of short-course radiotherapy (SC-RT) followed by chemotherapy before total mesorectal excision in high-risk locally advanced rectal cancer. A noteworthy concern is that the RAPIDO trial did not ensure that all patients in the control arm received adjuvant chemotherapy. This may bias statistical estimates in favour of the experimental arm if adjuvant chemotherapy is active in rectal cancer. Moreover, the 5-year update revealed an increase in the risk of local relapse in the experimental arm. MATERIALS AND METHODS: We carried out sensitivity analyses to determine how plausible effects of adjuvant chemotherapy, adjusted by the proportion of patients in the standard arm receiving adjuvant treatment, would have influenced the observed treatment effect estimate of the RAPIDO trial. The most plausible values for the benefit of adjuvant chemotherapy were determined by Bayesian re-analysis of a prior meta-analysis. RESULTS: The meta-analysis suggested that oxaliplatin/fluorouracil-based adjuvant chemotherapy may improve disease-free survival (DFS) in rectal cancer although the signal is weak [hazard ratio (HR) 0.84, 95% credible interval, 0.57-1.15]; probability of benefit (HR <1) was 91.2%. In the sensitivity analysis, the HR for disease-related treatment failure would remain <1, thus favouring total neoadjuvant therapy (TNT), on most occasions, but the null hypothesis would not have been rejected in various credible settings. For the RAPIDO data to be consistent with the null effect, a moderate benefit of adjuvant chemotherapy (HR for DFS between 0.75 and 0.80) and 70%-80% of exposed participants would suffice. CONCLUSION: The decision to make adjuvant chemotherapy optional in the standard arm may have biased the results in favour of the experimental arm, in a scenario in which TNT does not offset the increase in local recurrences after SC-RT.

BCMA-Targeted Biologic Therapies: The Next Standard of Care in Multiple Myeloma Therapy.

With recent advances in myeloma therapy, patients can achieve long-term remissions, but eventually relapses will occur. Triple-class refractory myeloma (disease that is refractory to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody) and penta-refractory myeloma (disease that is refractory to two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 antibody) are associated with a particularly poor prognosis, and novel treatments are desperately needed for these patients. Targeting B cell maturation antigen (BCMA), which is ubiquitously expressed on plasma cells, has emerged as a well-tolerated and highly efficacious strategy in patients with relapsed and refractory myeloma. Several mechanisms of targeting BCMA are currently under investigation, including antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T cells and natural killer (NK) cells, all with unique side effect profiles. Early phase clinical trials showed unprecedented response rates in highly refractory myeloma patients, leading to the recent approvals of some of these agents. Still, many questions remain with regard to this target, including how best to target it, how to treat patients who have progressed on a BCMA-targeting therapy, and whether response rates will deepen if these agents are used in earlier lines of therapy. In this review, we examine the rationale for targeting BCMA and summarize the data for several agents across multiple classes of BCMA-targeting therapeutics, paying special attention to the diverse mechanisms and unique challenges of each therapeutic class.

A Single-Arm Phase II Study to Evaluate Efficacy and Safety of First-Line Treatment With DCVAC/LuCa, Standard of Care Chemotherapy and Shenqi Fuzheng Injection in Advanced (Stage IIIB/IV) Non-Small Cell Lung Cancer Patients.

OBJECTIVES: To evaluate the efficacy and safety of first-line treatment with a dendritic cell vaccination for lung cancer (DCVAC/LuCa), standard of care chemotherapy and Shenqi Fuzheng injection in patients with advanced (stage IIIB/IV) non-small cell lung cancer. PATIENTS AND METHODS: Patients with histologically or cytologically confirmed recurrent metastatic or advanced NSCLC (stage IIIB/IV) with wild-type epidermal growth factor receptor (EGFR) or EGFR mutation which does not confer increased tumor susceptibility to EGFR-interacting drugs were recruited. For the treatment period, the first cycle of standard of care therapy (SoC) started 2 to 14 days after the leukapheresis procedure. SoC continued 4 to 6 cycles. DCVAC/LuCa was administered from the second cycle of SoC. DCVAC/LuCa was administered in a 3-week cycle schedule (5 doses) and then in a 6-week cycle schedule. Shenqi Fuzheng injection was administered 3 days before each DCVAC/LuCa administration for a total of 14 daily doses. Patients would undergo disease evaluation by computed tomography (CT) scan every 3 months. The primary and secondary endpoint was efficacy with regard to objective response rate (ORR) and progression free survival (PFS). The safety profile was measured by: incidence, type, and severity of all adverse events (AEs), laboratory abnormalities (blood routine test, urine test, and chemical test), physical status, and vital signs. Qi insufficiency was evaluated by tongue diagnosis and questionnaire survey with "Classification and Determination of constitution in TCM." RESULTS: Twenty-three patients from 3 hospitals who received combination therapy were included. ORR was 34.8% (95% CI:16.4%-57.3%). Median duration of response was 5.51 m (95% CI:2.70-8.32). Median PFS was 10.72 m (95% CI:4.52-16.93), 1-year survival was 77.8%. mOS was 21.97 m (95% CI:13.68-30.25). There was 1 severe AE related to a history of heart disease and there were no adverse events related to DCVAC/LuCa treatment. Qi insufficiency was improved significantly (P < .0001) from 41.19 ± 14.58 before treatment to 10.52 ± 16.58 after treatment. CONCLUSION: DCVAC/LuCa, combined with standard of care chemotherapy and Shenqi Fuzheng injection exhibited good benefit in Chinese patients with recurrent metastatic or advanced (stage IIIB/IV) NSCLC, and also significantly improved Qi insufficiency constitution. There were no related adverse events with DCVAC/LuCa treatment.

Australian health service organisation assessment outcome data for the first 2 years of implementing the Comprehensive Care Standard.

Objective To review implementation of the Comprehensive Care Standard (CCS) by evaluating assessment outcome data of Australian health service organisations (HSOs) from January 2019. The CCS was introduced with the National Safety and Quality Health Service (NSQHS) Standards (second edition). It has 36 actions and over 40 resources to support implementation. Methods Retrospective assessment outcome data submitted by accrediting agencies were examined to gauge progress of CCS implementation by considering met or other ratings of the CCS actions. Results There were 495 assessments completed between January 2019 and December 2020. Most (71% n = 352) HSOs met the requirements of the CCS after initial assessment. Seventy-four (15%) of the HSOs did not meet all the requirements and a further 58 (12%) HSOs were provided with recommendations to meet the actions. Conclusions There was indication of underperformance related to some actions in the CCS. The assessment data highlighted common issues for organisations including difficulties implementing governance processes, demonstrating effective care planning, implementing the end-of-life care actions and some minimising harm actions. Future evaluation of the implementation of the CCS may benefit from strengthening links between other safety and quality programs.

Development of a standard of care for patients with valosin-containing protein associated multisystem proteinopathy.

Valosin-containing protein (VCP) associated multisystem proteinopathy (MSP) is a rare inherited disorder that may result in multisystem involvement of varying phenotypes including inclusion body myopathy, Paget's disease of bone (PDB), frontotemporal dementia (FTD), parkinsonism, and amyotrophic lateral sclerosis (ALS), among others. An international multidisciplinary consortium of 40+ experts in neuromuscular disease, dementia, movement disorders, psychology, cardiology, pulmonology, physical therapy, occupational therapy, speech and language pathology, nutrition, genetics, integrative medicine, and endocrinology were convened by the patient advocacy organization, Cure VCP Disease, in December 2020 to develop a standard of care for this heterogeneous and under-diagnosed disease. To achieve this goal, working groups collaborated to generate expert consensus recommendations in 10 key areas: genetic diagnosis, myopathy, FTD, PDB, ALS, Charcot Marie Tooth disease (CMT), parkinsonism, cardiomyopathy, pulmonology, supportive therapies, nutrition and supplements, and mental health. In April 2021, facilitated discussion of each working group's conclusions with consensus building techniques enabled final agreement on the proposed standard of care for VCP patients. Timely referral to a specialty neuromuscular center is recommended to aid in efficient diagnosis of VCP MSP via single-gene testing in the case of a known familial VCP variant, or multi-gene panel sequencing in undifferentiated cases. Additionally, regular and ongoing multidisciplinary team follow up is essential for proactive screening and management of secondary complications. The goal of our consortium is to raise awareness of VCP MSP, expedite the time to accurate diagnosis, define gaps and inequities in patient care, initiate appropriate pharmacotherapies and supportive therapies for optimal management, and elevate the recommended best practices guidelines for multidisciplinary care internationally.

Local anaesthesia as a standard of care for penetrating keratoplasty?

BACKGROUND/OBJECTIVES: To determine preferences in the use of local anaesthesia (LA) versus general anaesthesia (GA) for penetrating keratoplasty (PK), and to examine the safety of LA for PK. SUBJECTS/METHODS: A retrospective analysis of PKs performed at an ophthalmology department in Canada from 01/01/2008 to 01/01/2020 was conducted to investigate rate of major complications. A questionnaire was also sent out to cornea specialists in the United Kingdom (UK) and Canada to determine trends in anaesthesia use for PK. Data on anaesthesia use in keratoplasty data was also obtained from the National Health Service Blood and Tissue (NHSBT) register. RESULTS: The retrospective study found that 2143 PKs were performed under LA by 4 surgeons. The following complications were revealed: 1 acute anxiety attack with tachycardia, 3 extraocular myotoxicity cases requiring squint surgery, 1 expulsive suprachoroidal haemorrhage and 1 retrobulbar haemorrhage. The survey revealed 92% of cornea specialists in Canada preferred LA to GA. In the UK, 4.5% of specialists preferred LA, with most preferring GA due to suprachoroidal haemorrhage risk. NHSBT data revealed that 86.6% of 6181 PKs performed in UK between 01/04/2015 and 31/03/2020 were done under GA. CONCLUSIONS: LA is preferred for PK in Canada, in contrast to the UK where GA is preferred. Our retrospective study suggests a low incidence of LA-related complications. We suggest that LA should be considered for most cornea transplant techniques, including optical penetrating keratoplasty. Rising worldwide keratoplasty numbers, ageing populations and risks of pandemics (e.g. COVID-19) give more reason for reduced reliance on GA.

Academy of Nutrition and Dietetics Nutrition Research Network: A Home Garden Intervention Improves Child Length-for-Age Z-Score and Household-Level Crop Count and Nutritional Functional Diversity in Rural Guatemala.

Home gardens may help address childhood malnutrition in low- and middle-income countries. In this quasi-experimental pilot study, the Academy of Nutrition and Dietetics, in collaboration with Maya Health Alliance, evaluated the feasibility of augmenting a standard-of-care nutrition-specific package for Maya children with length-for-age z score ≤-2 (stunting) in rural Guatemala with a nutrition-sensitive home garden intervention. Two agrarian municipalities in Guatemala were included. Families of 70 children with stunting from 1 municipality received the standard-of-care package (food supplementation, multiple micronutrient powders, monthly nutrition home visits, group nutrition classes). Families of 70 children with stunting from another municipality received the standard-of-care package plus a home garden intervention (garden materials, monthly agricultural home visits, agriculture classes). Maternal and child dietary diversity, household food insecurity, child growth, and agricultural indicators were collected at baseline and 6 months later and were analyzed using mixed linear and logistic regression models. Compared with the standard-of-care group, the garden intervention group had improved child (odds ratio [OR] 3.66, 95% CI 0.89-15.10, P = 0.07) and maternal dietary diversity (OR 2.31, 95% CI 0.80-6.65, P = 0.12) and decreased food insecurity (OR 0.38, 95% CI 0.11-1.35, P = 0.14); however, these effects were not statistically significant. Participation in gardens predicted a higher length-for-age z-score (change difference [CD] 0.22 SD, 95% CI 0.05-0.38, P = 0.009), greater crop species count (CD 2.97 crops, 95% CI 1.79-4.16, P < 0.001), and greater nutritional functional diversity (CD 0.04 points, 95% CI 0.01-0.07, P = 0.006) than standard-of-care alone. Home garden interventions are feasible in rural Guatemala and may have potential benefits for child growth when added to other nutrition-specific interventions.

Rapid genomic testing for critically ill children: time to become standard of care?

Rapid genomic testing in critically ill neonatal and paediatric patients has transformed the paradigm of rare disease diagnosis, delivering results in real time to inform patient management. More than 20 studies totalling over 1500 patients from diverse healthcare settings worldwide have now been published, forming a compelling evidence base for healthcare system implementation. We review the reported diagnostic and clinical outcomes, as well as broader evaluations of family and professional experiences, cost effectiveness, implementation challenges and bioethical issues arising from rapid testing. As rapid genomic testing transitions from the research to the healthcare setting to become a 'standard of care' test, there is a need to develop effective service delivery models to support scalability at both the laboratory and clinical level and promote equity of access, prompt test initiation, integrated multidisciplinary input and holistic family support. Harnessing the high level of professional engagement with rapid genomic testing programmes will continue to drive innovation and adoption, while close integration with emerging precision medicine approaches will be necessary to deliver on the promise of reduced infant and child mortality.

Investigator-Driven Randomised Controlled Trial of Cefiderocol versus Standard Therapy for Healthcare-Associated and Hospital-Acquired Gram-negative Bloodstream Infection: Study protocol (the GAME CHANGER trial): study protocol for an open-label, randomised controlled trial.

BACKGROUND: Increasing rates of antibiotic resistance in Gram-negative organisms due to the presence of extended-spectrum beta-lactamases (ESBL), hyperproduction of AmpC enzymes, carbapenemases and other mechanisms of resistance are identified in common hospital- and healthcare-associated pathogens including Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. Cefiderocol is a novel siderophore cephalosporin antibiotic with a catechol moiety on the 3-position side chain. Cefiderocol has been shown to be potent in vitro against a broad range of Gram-negative organisms, including carbapenem-resistant Enterobacteriaceae (CRE) and multi-drug-resistant (MDR) P. aeruginosa and A. baumannii. Recent clinical data has shown cefiderocol to be effective in the setting of complicated urinary tract infections and nosocomial pneumonia, but it has not yet been studied as treatment of bloodstream infection. METHODS: This study will use a multicentre, open-label non-inferiority trial design comparing cefiderocol and standard of care antibiotics. Eligible participants will be adult inpatients who are diagnosed with a bloodstream infection with a Gram-negative organism on the basis of a positive blood culture result where the acquisition meets the definition for healthcare-associated or hospital-acquired. It will compare cefiderocol with the current standard of care (SOC) antibiotic regimen according to the patient's treating clinician. Eligible participants will be randomised 1:1 to cefiderocol or SOC and receive 5-14 days of antibiotic therapy. Trial recruitment will occur in at least 20 sites in ten countries (Australia, Malaysia, Singapore, Thailand, Turkey and Greece). The sample size has been derived from an estimated 14 day, all-cause mortality rate of 10% in the control group, and a non-inferiority margin of 10% difference in the two groups. A minimum of 284 patients are required in total to achieve 80% power with a two-sided alpha level of 0.05. Data describing demographic information, risk factors, concomitant antibiotics, illness scores, microbiology, multidrug-resistant organism screening, discharge and mortality will be collected. DISCUSSION: With increasing antimicrobial resistance, there is a need for the development of new antibiotics with broad activity against Gram-negative pathogens such as cefiderocol. By selecting a population at risk for multi-drug-resistant pathogens and commencing study treatment early in the clinical illness (within 48 h of index blood culture) the trial hopes to provide guidance to clinicians of the efficacy of this novel agent. TRIAL REGISTRATION: The GAME CHANGER trial is registered under the US National Institute of Health ClinicalTrials.gov register, reference number NCT03869437 . Registered on March 11, 2019.