'Access to Radiotherapy for Cancer treatment (ARC) Project': Guidance for low and middle-income countries establishing safe and sustainable radiotherapy services

University of Technology Sydney. Faculty of Health.: Efforts to improve access to cancer care, including radiotherapy services in low and middle-income countries (LMICs) is challenging. Many radiotherapy initiatives in LMICs have failed to fully deliver on their promise because of multi-faceted barriers at the systems, organisational and patient levels, leading to significant wastage of scarce resources. Greater guidance on how to assess and build LMICs’ readiness for establishing sustainable radiotherapy services is needed to improve cancer care outcomes in LMICs. : The ‘ccess to adiotherapy for ancer treatment (ARC) Project’ aimed to provide practical guidance to LMICs on establishing safe and sustainable radiotherapy services. : The mixed qualitative methods ARC Project involved a: systematic review; and two-part qualitative study. The systematic review synthesised strategies adopted by LMICs to improve access to cancer treatment and palliative care. Semi-structured interviews undertaken with global radiotherapy experts explored perceived facilitators and barriers to establishing sustainable radiotherapy services in LMICs. The mid-point meta-inference of the systematic review and semi-structured interview data generated a draft list of requirements, which was circulated to global experts during the second part-of the qualitative study. The final meta-inference was undertaken following the completion of the three studies. : The systematic review identified that comparatively few studies have focused specifically on improving radiotherapy in LMICs, with no research evaluating effectiveness. The semi-structured interviews identified three key facilitators to establishing sustainable radiotherapy services in LMICs, namely: committing to a vision of improving cancer care; making it happen and sustaining a safe service; and leveraging off radiotherapy to strengthen integrated cancer care. The mid-point meta-inference generated 42 potential requirements, which were organised into four readiness domains: commitment (n=13); cooperation (n=7); capacity (n=17); and catalyst (n=5). The participant validation confirmed 37 of the generated requirements as relevant for inclusion in a radiotherapy service development readiness self-assessment guide for use by LMICs. The end-point meta-inference of the ARC Project’s integrated data presented the ‘adiness lf-ssessment (RESEA) Guide’, with 120 questions that may help LMICs at macro and meso level to determine and create action plans to improve their readiness to establish radiotherapy services. : The ARC Project has identified a complex combination of facilitators and barriers that influence the establishment of sustainable radiotherapy services in LMICs. It has developed a RESEA Guide to provide support for LMICs seeking to establish sustainable radiotherapy services. Further work is needed to evaluate the acceptability and feasibility of the RESEA Guide and inform further refinements

Consumer acceptability and antidiabetic properties of flakes and crackers developed from selected native Australian plant species

Type 2 diabetes, linked to an unhealthy diet, is increasing in Australia. This study aimed to evaluate the acceptability of potential antidiabetic food preventatives followed by phyto-component detection by high-performance liquid chromatography analysis and glycaemic index (GI) estimation by in vitro enzymatic hydrolysis. Five flakes and a cracker were developed from Acacia longifolia seeds, Typha orientalis rhizomes and Rhagodia candolleana berries. Samples were tested for consumer acceptability against a commercially available flake and cracker (as controls) by 44 participants using a 9-point hedonic scale. Overall acceptability of 86.4% and 54.5%–65.9% was recorded against control and test flakes, while control and test crackers recorded 84.1% and 70.5%, respectively. The test cracker contained gallic acid (GA) and ρ-coumaric acid (PCA) with GI, 47.7 ± 1.3, whereas control cracker contained GA and had GI, 70.3 ± 2.5. These results indicate that the test cracker may have potential as an antidiabetic food preventative

The effect of malting on phenolic compounds and radical scavenging activity in grains and breakfast cereals

Abstract: Breakfast cereals are popular grain foods and sources of polyphenols. Malting alters polyphenol content and activity; however, effects are varied. The total polyphenol content (TPC), radical scavenging activity (RSA), and polyphenol profile were analyzed in unmalted and malted grains (wheat, barley, and sorghum) and breakfast cereals (wheat, barley) by Folin Ciocalteu Reagent (FCR), % inhibition of the free radical 2,2-diphenyl-1-picryl-hydrazyl, and high performance liquid chromatography. Higher TPC was observed in all malted grains and breakfast cereals compared with unmalted samples (p < 0.05). Higher RSA was also observed in all malted samples compared to unmalted samples (p < 0.05) except for wheat grain to malted wheat grain. In this study, malting induced additional polyphenols and antioxidant activity in grains and cereal products. Malted grain breakfast cereals may be practical sources of polyphenol antioxidants. Practical Application: This study utilized malting in a unique way to investigate potential health benefits of polyphenols and antioxidant activity in grains (wheat, barley, and sorghum) and ready-to-eat breakfast cereals (wheat and barley). This study found that grains and breakfast cereals are important sources of antioxidant polyphenols, and these were significantly increased in malted varieties. Understanding this is important as grains and breakfast cereals are widely consumed staple foods. Consuming healthier grain products may be a practical strategy in reducing the risk of noncommunicable diseases such as colorectal cancer and type-2 diabetes, where wholegrain consumption may be important in prevention

Novel coronavirus mitigation measures implemented by radiotherapy centres in low and middle-income countries: a systematic review

Background: The aim of the study was to identify strategies adopted by radiotherapy centres in low- and middle-income countries (LMICs) to mitigate the effects of COVID-19. Studies summarising COVID-19 mitigation strategies designed and implemented by radiotherapy centres in LMICs to avoid delays, deferrments and interruptions of radiotherapy services are lacking. Materials and methods: A systematic review was conducted and reported in accordance with the preferred reporting items for systematic review and meta-analysis guideline. Ovid Embase, Ovid MEDLINE and CINAHL were searched for peer-reviewed articles that reported measures adopted by radiotherapy centres in LMICs to reduce the risk of COVID-19. Information on different strategies were extracted from the included studies and textual narrative synthesis was conducted. Results: Of 60 articles retrieved, eleven were included. Majority of the studies were conducted in China. Ten of the included studies employed a qualitative design. Four themes were identified: preparing and equipping staff; reinforcing infection prevention and control policies; strengthening coordination and communication; and maintaining physical distancing. Studies reported that radiotherapy centres had: formed COVID-19 response multidisciplinary team; maximised the use of telehealth; adjusted the layout of waiting areas; divided staff into teams; dedicated a room for isolating suspected cases; and adopted triage systems. Conclusions: Local adaptation of established global strategies coupled with timely development of guidelines, flexibility and innovation have allowed radiotherapy leaders to continue to deliver radiotherapy services to cancer patients in LMICs during the COVID-19 crisis. Robust data collection must be encouraged in LMICs to provide an evidence-based knowledge for use in the event of another pandemic

Zinc as an adjunct therapy in the management of severe pneumonia among Gambian children: randomized controlled trial.

BACKGROUND: The benefit of zinc as an adjunct therapy for severe pneumonia is not established. We assessed the benefit of adjunct zinc therapy for severe pneumonia in children and determined whether the study children were zinc deficient. METHODS: This was a randomized, parallel group, double-blind, placebo-controlled trial with an allocation ratio of 1:1 conducted in children with severe pneumonia to evaluate the efficacy of daily zinc as an adjunct treatment in preventing 'treatment failure' (presence of any sign of severe pneumonia) on day-5 and day-10 and in reducing the time to resolution of signs of severe pneumonia. Six hundred and four children 2-59 months of age presenting with severe pneumonia at six urban and rural health care facilities in The Gambia were individually randomised to receive placebo (n = 301) or zinc (n = 303) for seven days. To determine if the study children were zinc deficient, supplementation was continued in a randomly selected subgroup of 121 children from each arm for six months post-enrolment, and height-gain, nutritional status, plasma zinc concentrations, and immune competence were compared. RESULTS: Percentage of treatment failure were similar in placebo and zinc arms both on day 5 (14.0% vs 14.1%) and day 10 (5.2% vs 5.9%). The time to recovery from lower chest wall indrawing and sternal retraction was longer in the placebo compared to zinc arm (24.4 vs 23.0 hours; P = 0.011 and 18.7 vs 11.0 hours; P = 0.006 respectively). The time to resolution for all respiratory symptoms of severity was not significantly different between placebo and zinc arms (42.3 vs 30.9 hours respectively; P = 0.242). In the six months follow-up sub-group, there was no significant difference in height gain, height-for-age and weight-for-height Z-scores, mid upper arm circumference, plasma zinc concentrations, and anergy at six months post-enrolment. CONCLUSIONS: In this population, zinc given as an adjunct treatment for severe pneumonia showed no benefit in treatment failure rates, or clinically important benefit in time to recovery from respiratory symptoms and showed marginal benefit in rapidity of resolution of some signs of severity. This finding does not support routine use of zinc as an adjunct treatment in severe pneumonia in generally zinc replete children. TRIAL REGISTRATION: ISRCTN33548493

Pneumococcal carriage in sub-Saharan Africa--a systematic review.

BACKGROUND: Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. METHODS: A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. RESULTS: Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6-70.8) in children less than 5 years, 42.6% (95% CI: 29.9-55.4) in children 5-15 years and 28.0% (95% CI: 19.0-37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9-24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. CONCLUSION: Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination

A Phosphatidic Acid Binding/Nuclear Localization Motif Determines Lipin1 Function in Lipid Metabolism and Adipogenesis

A polybasic motif in the metabolic regulator lipin1 is both a membrane anchor and a nuclear localization sequence required for lipin1 function in phospholipid metabolism and adipogenesis

Study protocol for a phase 1/2, single-centre, double-blind, double-dummy, randomized, active-controlled, age de-escalation trial to assess the safety, tolerability and immunogenicity of a measles and rubella vaccine delivered by a microneedle patch in healthy adults (18 to 40 years), measles and rubella vaccine-primed toddlers (15 to 18 months) and measles and rubella vaccine-naïve infants (9 to 10 months) in The Gambia [Measles and Rubella Vaccine Microneedle Patch Phase 1/2 Age De-escalation Trial].

BACKGROUND: New strategies to increase measles and rubella vaccine coverage, particularly in low- and middle-income countries, are needed if elimination goals are to be achieved. With this regard, measles and rubella vaccine microneedle patches (MRV-MNP), in which the vaccine is embedded in dissolving microneedles, offer several potential advantages over subcutaneous delivery. These include ease of administration, increased thermostability, an absence of sharps waste, reduced overall costs and pain-free administration. This trial will provide the first clinical trial data on MRV-MNP use and the first clinical vaccine trial of MNP technology in children and infants. METHODS: This is a phase 1/2, randomized, active-controlled, double-blind, double-dummy, age de-escalation trial. Based on the defined eligibility criteria for the trial, including screening laboratory investigations, 45 adults [18-40 years] followed by 120 toddlers [15-18 months] and 120 infants [9-10 months] will be enrolled in series. To allow double-blinding, participants will receive either the MRV-MNP and a placebo (0.9% sodium chloride) subcutaneous (SC) injection or a placebo MNP and the MRV by SC injection (MRV-SC). Local and systemic adverse event data will be collected for 14 days following study product administration. Safety laboratories will be repeated on day 7 and, in the adult cohort alone, on day 14. Unsolicited adverse events including serious adverse events will be collected until the final study visit for each participant on day 180. Measles and rubella serum neutralizing antibodies will be measured at baseline, on day 42 and on day 180. Cohort progression will be dependent on review of the unblinded safety data by an independent data monitoring committee. DISCUSSION: This trial will provide the first clinical data on the use of a MNP to deliver the MRV and the first data on the use of MNPs in a paediatric population. It will guide future product development decisions for what may be a key technology for future measles and rubella elimination. TRIAL REGISTRATION: Pan-African Clinical Trials Registry 202008836432905 . CLINICALTRIALS: gov NCT04394689

A measles and rubella vaccine microneedle patch in The Gambia: a phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial.

BACKGROUND: Microneedle patches (MNPs) have been ranked as the highest global priority innovation for overcoming immunisation barriers in low-income and middle-income countries. This trial aimed to provide the first data on the tolerability, safety, and immunogenicity of a measles and rubella vaccine (MRV)-MNP in children. METHODS: This single-centre, phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial was conducted in The Gambia. To be eligible, all participants had to be healthy according to prespecified criteria, aged 18-40 years for the adult cohort, 15-18 months for toddlers, or 9-10 months for infants, and to be available for visits throughout the follow-up period. The three age cohorts were randomly assigned in a 2:1 ratio (adults) or 1:1 ratio (toddlers and infants) to receive either an MRV-MNP (Micron Biomedical, Atlanta, GA, USA) and a placebo (0·9% sodium chloride) subcutaneous injection, or a placebo-MNP and an MRV subcutaneous injection (MRV-SC; Serum Institute of India, Pune, India). Unmasked staff ransomly assigned the participants using an online application, and they prepared visually identical preparations of the MRV-MNP or placebo-MNP and MRV-SC or placebo-SC, but were not involved in collecting endpoint data. Staff administering the study interventions, participants, parents, and study staff assessing trial endpoints were masked to treatment allocation. The safety population consists of all vaccinated participants, and analysis was conducted according to route of MRV administration, irrespective of subsequent protocol deviations. The immunogenicity population consisted of all vaccinated participants who had a baseline and day 42 visit result available, and who had no protocol deviations considered to substantially affect the immunogenicity endpoints. Solicited local and systemic adverse events were collected for 14 days following vaccination. Unsolicited adverse events were collected to day 180. Age de-escalation between cohorts was based on the review of the safety data to day 14 by an independent data monitoring committee. Serum neutralising antibodies to measles and rubella were measured at baseline, day 42, and day 180. Analysis was descriptive and included safety events, seroprotection and seroconversion rates, and geometric mean antibody concentrations. The trial was registered with the Pan African Clinical Trials Registry PACTR202008836432905, and is complete. FINDINGS: Recruitment took place between May 18, 2021, and May 27, 2022. 45 adults, 120 toddlers, and 120 infants were randomly allocated and vaccinated. There were no safety concerns in the first 14 days following vaccination in either adults or toddlers, and age de-escalation proceeded accordingly. In infants, 93% (52/56; 95% CI 83·0-97·2) seroconverted to measles and 100% (58/58; 93·8-100) seroconverted to rubella following MRV-MNP administration, while 90% (52/58; 79·2-95·2) and 100% (59/59; 93·9-100) seroconverted to measles and rubella respectively, following MRV-SC. Induration at the MRV-MNP application site was the most frequent local reaction occurring in 46 (77%) of 60 toddlers and 39 (65%) of 60 infants. Related unsolicited adverse events, most commonly discolouration at the application site, were reported in 35 (58%) of 60 toddlers and 57 (95%) of 60 infants that had received the MRV-MNP. All local reactions were mild. There were no related severe or serious adverse events. INTERPRETATION: The safety and immunogenicity data support the accelerated development of the MRV-MNP. FUNDING: Bill & Melinda Gates Foundation

Association of diabetes, smoking, and alcohol use with subclinical-to-symptomatic spectrum of tuberculosis in 16 countries: an individual participant data meta-analysis of national tuberculosis prevalence surveys

Summary Background Non-communicable diseases (NCDs) and NCD risk factors, such as smoking, increase the risk for tuberculosis (TB). Data are scarce on the risk of prevalent TB associated with these factors in the context of population-wide systematic screening and on the association between NCDs and NCD risk factors with different manifestations of TB, where ∼50% being asymptomatic but bacteriologically positive (subclinical). We did an individual participant data (IPD) meta-analysis of national and sub-national TB prevalence surveys to synthesise the evidence on the risk of symptomatic and subclinical TB in people with NCDs or risk factors, which could help countries to plan screening activities. Methods In this systematic review and IPD meta-analysis, we identified eligible prevalence surveys in low-income and middle-income countries that reported at least one NCD (e.g., diabetes) or NCD risk factor (e.g., smoking, alcohol use) through the archive maintained by the World Health Organization and by searching in Medline and Embase from January 1, 2000 to August 10, 2021. The search was updated on March 23, 2023. We performed a one-stage meta-analysis using multivariable multinomial models. We estimated the proportion of and the odds ratio for subclinical and symptomatic TB compared to people without TB for current smoking, alcohol use, and self-reported diabetes, adjusted for age and gender. Subclinical TB was defined as microbiologically confirmed TB without symptoms of current cough, fever, night sweats, or weight loss and symptomatic TB with at least one of these symptoms. We assessed heterogeneity using forest plots and I2 statistic. Missing variables were imputed through multi-level multiple imputation. This study is registered with PROSPERO (CRD42021272679). Findings We obtained IPD from 16 national surveys out of 21 national and five sub-national surveys identified (five in Asia and 11 in Africa, N = 740,815). Across surveys, 15.1%–56.7% of TB were subclinical (median: 38.1%). In the multivariable model, current smoking was associated with both subclinical (OR 1.67, 95% CI 1.27–2.40) and symptomatic TB (OR 1.49, 95% CI 1.34–1.66). Self-reported diabetes was associated with symptomatic TB (OR 1.67, 95% CI 1.17–2.40) but not with subclinical TB (OR 0.92, 95% CI 0.55–1.55). For alcohol drinking ≥ twice per week vs no alcohol drinking, the estimates were imprecise (OR 1.59, 95% CI 0.70–3.62) for subclinical TB and OR 1.43, 95% CI 0.59–3.46 for symptomatic TB). For the association between current smoking and symptomatic TB, I2 was high (76.5% (95% CI 62.0–85.4), while the direction of the point estimates was consistent except for three surveys with wide CIs. Interpretation Our findings suggest that current smokers are more likely to have both symptomatic and subclinical TB. These individuals can, therefore, be prioritised for intensified screening, such as the use of chest X-ray in the context of community-based screening. People with self-reported diabetes are also more likely to have symptomatic TB, but the association is unclear for subclinical TB