Automatic Classification of Antimalarial Herbal Drugs Exposed to Ultraviolet Radiation from Unexposed Ones Using Laser-Induced Autofluorescence with Chemometric Techniques.

Exposure of antimalarial herbal drugs (AMHDs) to ultraviolet radiation (UVR) affects the potency and integrity of the AMHDs. Instant classification of the AMHDs exposed to UVR (UVR-AMHDs) from unexposed ones (Non-UVR-AMHDs) would be beneficial for public health safety, especially in warm regions. For the first time, this work combined laser-induced autofluorescence (LIAF) with chemometric techniques to classify UVR-AMHDs from Non-UVR-AMHDs. LIAF spectra data were recorded from 200 ml of each of the UVR-AMHDs and Non-UVR-AMHDs. To extract useful data from the spectra fingerprint, principal components (PCs) analysis was used. The performance of five chemometric algorithms: random forest (RF), neural network (NN), support vector machine (SVM), linear discriminant analysis (LDA), and k-nearest neighbour (KNN), were compared after optimization by validation. The chemometric algorithms showed that KNN, SVM, NN, and RF were superior with a classification accuracy of 100% for UVR-AMHDs while LDA had a classification accuracy of 98.8% after standardization of the spectra data and was used as an input variable for the model. Meanwhile, a classification accuracy of 100% was obtained for KNN, LDA, SVM, and NN when the raw spectra data was used as input except for RF for which a classification accuracy of 99.9% was obtained. Classification accuracy above 99.74 ± 0.26% at 3 PCs in both the training and testing sets were obtained from the chemometric models. The results showed that the LIAF, combined with the chemometric techniques, can be used to classify UVR-AMHDs from Non-UVR-AMHDs for consumer confidence in malaria-prone regions. The technique offers a non-destructive, rapid, and viable tool for identifying UVR-AMHDs in resource-poor countries.

Absorption-invariant focusing efficiency for wavefront-shaping controlled reflection from absorbing disordered media.

We numerically model the influence of absorption on wavefront-shaping controlled reflection from absorbing disordered media and provide experimental verification of our model. We find that absorption modifies the reflection eigenvalue density, the average reflectance, and the reflection matrix element density. However, we also find that despite these effects, the efficiency of wavefront-shaping controlled reflection is invariant with absorption.

A language-matching model to improve equity and efficiency of COVID-19 contact tracing.

Contact tracing is a pillar of COVID-19 response, but language access and equity have posed major obstacles. COVID-19 has disproportionately affected minority communities with many non-English-speaking members. Language discordance can increase processing times and hamper the trust building necessary for effective contact tracing. We demonstrate how matching predicted patient language with contact tracer language can enhance contact tracing. First, we show how to use machine learning to combine information from sparse laboratory reports with richer census data to predict the language of an incoming case. Second, we embed this method in the highly demanding environment of actual contact tracing with high volumes of cases in Santa Clara County, CA. Third, we evaluate this language-matching intervention in a randomized controlled trial. We show that this low-touch intervention results in 1) significant time savings, shortening the time from opening of cases to completion of the initial interview by nearly 14 h and increasing same-day completion by 12%, and 2) improved engagement, reducing the refusal to interview by 4%. These findings have important implications for reducing social disparities in COVID-19; improving equity in healthcare access; and, more broadly, leveling language differences in public services.

Reproductive history and breast cancer survival: Findings from the African breast cancer-Disparities in outcomes cohort and implications of Africa's fertility transition on breast cancer prognosis.

Reproductive characteristics are known risk factors for breast cancer but, other than recent birth, their role as prognostic factors is less clear, and has not been studied in Sub-Saharan Africa (SSA). In this setting, we examined whether reproductive factors independently influence breast cancer survival in a subset of the African Breast Cancer-Disparities in Outcomes cohort study. In 1485 women with incident breast cancer recruited between 2014 and 2017, we examined birth cohort changes in reproductive factors, and used Cox models to examine whether reproductive characteristics were associated with all-cause mortality after adjusting for confounders (age, stage, treatment, HIV, and social factors). Four years after diagnosis, 822 (56%) women had died. Median parity was 4 (IQR = 2, 6) and 209 (28%) of premenopausal women had had a recent birth (<3 years prior to cancer diagnosis). Each pregnancy was associated with a 5% increase (95% CI: 2%, 8%) in mortality rates, which held among postmenopausal women (5%, [1%-9%]). Pre-menopausal women with a recent birth had 52% (20%, 92%) higher mortality rates. Fertility trends by birth cohort showed declining parity, increasing age at first birth and declining age at last birth, however the impact of these population-level changes on future average survival was predicted to be very small (<3% absolute gain).

Self-reported health change in haemodialysis recipients modulates the effect of frailty upon mortality and hospital admissions: outcomes from a large prospective UK cohort.

BACKGROUND: Frailty among haemodialysis patients is associated with hospitalization and mortality, but high frailty prevalence suggests further discrimination of risk is required. We hypothesized that incorporation of self-reported health with frailty measurement may aid risk stratification. METHODS: Prospective cohort study of 485 prevalent haemodialysis recipients linked to English national datasets. Frailty Phenotype (FP), Frailty Index (FI), Edmonton Frail Scale (EFS), Clinical Frailty Scale (CFS) and self-reported health change were assessed. Mortality was explored using Fine and Gray regression, and admissions by negative binomial regression. RESULTS: Over a median 678 (interquartile range 531-812) days, there were 111 deaths, and 1241 hospitalizations. Increasing frailty was associated with mortality on adjusted analyses for FP [subdistribution hazard ratio (SHR) 1.26, 95% confidence interval (CI) 1.05-1.53, P = .01], FI (SHR 1.21, 95% CI 1.09-1.35, P = .001) and CFS (SHR 1.32, 95% CI 1.11-1.58, P = .002), but not EFS (HR 1.08, 95% CI 0.99-1.18, P = .1). Health change interacted with frailty tools to modify association with mortality; only those who rated their health as the same or worse experienced increased mortality hazard associated with frailty by FP (Pinteraction = .001 and 0.035, respectively), FI (Pinteraction = .002 and .007, respectively) and CFS (Pinteraction = .009 and 0.02, respectively). CFS was the only frailty tool associated with hospitalization (incidence rate ratio 1.12, 95% CI 1.02-1.23, P = .02). CONCLUSIONS: We confirm the high burden of hospitalization and mortality associated with haemodialysis patients regardless of frailty tool utilized and introduce the discriminatory ability of self-reported health to identify the most at-risk frail individuals.

Global Breast Cancer Initiative: A platform to address the psycho-oncology of cancer in low- and middle-income countries for improving global breast cancer outcomes.

BACKGROUND: Psycho-oncology is a clinical specialty in which the humanistic aspects of cancer diagnoses and treatment are addressed to reduce the psychological burden for patients and their caregivers to optimize patient participation, cancer outcomes and quality-of-life, which is especially critical in cultures where cancer is perceived as invariably fatal. Psycho-oncology programs face multiple barriers in low- and middle-income countries, including limited resource allocation and lack of training, both of which have been impediments to psycho-oncology programs becoming recognized as core competencies in cancer management and part of a standard medical curriculum. PURPOSE: This paper discusses the role of the Global Breast Cancer Initiative (GBCI) in helping to overcome inequities in breast cancer care and improve clinical outcomes from a psycho-oncology perspective as a model for improved cancer care in limited resource settings. FINDINGS: GBCI applies a comprehensive framework encompassing all phases of cancer care (defined through three pillars spanning the continuum of cancer management) and includes addressing the physical, psychological, and social needs of women throughout the life-course. Efforts to promote policies that increase access to early detection and treatment programs and improve health literacy among the public are important strategies to mitigate the most common emotional and physical challenges reported by people with cancer accessing care. CONCLUSIONS: Future efforts will focus on the integration of culturally appropriate guidance to promote early cancer detection and treatment completion through training programs for clinicians to establish core competencies in psycho-oncology. Emerging advocacy efforts in the oncology arena may help guide the integration of psycho-oncology services into routine care in countries where these services are not already integrated into the standard curriculum.

Classification of Organic and Conventional Cocoa Beans Using Laser-Induced Fluorescence Spectroscopy Combined with Chemometric Techniques.

The craving for organic cocoa beans has resulted in fraudulent practices such as mislabeling, adulteration, all known as food fraud, prompting the international cocoa market to call for the authenticity of organic cocoa beans before export. In this study, we proposed robust models using laser-induced fluorescence (LIF) and chemometric techniques for rapid classification of cocoa beans as either organic or conventional. The LIF measurements were conducted on cocoa beans harvested from organic and conventional farms. From the results, conventional cocoa beans exhibited a higher fluorescence intensity compared to organic ones. In addition, a general peak wavelength shift was observed when the cocoa beans were excited using a 445 nm laser source. These results highlight distinct characteristics that can be used to differentiate between organic and conventional cocoa beans. Identical compounds were found in the fluorescence spectra of both the organic and conventional ones. With preprocessed fluorescence spectra data and utilizing principal component analysis, classification models such as Linear Discriminant Analysis (LDA), Support Vector Machine (SVM), Neural Network (NN) and Random Forest (RF) models were employed. LDA and NN models yielded 100.0% classification accuracy for both training and validation sets, while 99.0% classification accuracy was achieved in the training and validation sets using SVM and RF models. The results demonstrate that employing a combination of LIF and either LDA or NN can be a reliable and efficient technique to classify authentic cocoa beans as either organic or conventional. This technique can play a vital role in maintaining integrity and preventing fraudulent practices in the cocoa bean supply chain.

A clinical frailty scale obtained from MDT discussion performs poorly in assessing frailty in haemodialysis recipients.

BACKGROUND: The Clinical Frailty Scale (CFS) is a commonly utilised frailty screening tool that has been associated with hospitalisation and mortality in haemodialysis recipients, but is subject to heterogenous methodologies including subjective clinician opinion. The aims of this study were to (i) examine the accuracy of a subjective, multidisciplinary assessment of CFS at haemodialysis Quality Assurance (QA) meetings (CFS-MDT), compared with a standard CFS score via clinical interview, and (ii) ascertain the associations of these scores with hospitalisation and mortality. METHODS: We performed a prospective cohort study of prevalent haemodialysis recipients linked to national datasets for outcomes including mortality and hospitalisation. Frailty was assessed using the CFS after structured clinical interview. The CFS-MDT was derived from consensus at haemodialysis QA meetings, involving dialysis nurses, dietitians, and nephrologists. RESULTS: 453 participants were followed-up for a median of 685 days (IQR 544-812), during which there were 96 (21.2%) deaths and 1136 hospitalisations shared between 327 (72.1%) participants. Frailty was identified in 246 (54.3%) participants via CFS, but only 120 (26.5%) via CFS-MDT. There was weak correlation (Spearman Rho 0.485, P < 0.001) on raw frailty scores and minimal agreement (Cohen's κ = 0.274, P < 0.001) on categorisation of frail, vulnerable and robust between the CFS and CFS-MDT. Increasing frailty was associated with higher rates of hospitalisation for the CFS (IRR 1.26, 95% C.I. 1.17-1.36, P = 0.016) and CFS-MDT (IRR 1.10, 1.02-1.19, P = 0.02), but only the CFS-MDT was associated with nights spent in hospital (IRR 1.22, 95% C.I. 1.08-1.38, P = 0.001). Both scores were associated with mortality (CFS HR 1.31, 95% C.I. 1.09-1.57, P = 0.004; CFS-MDT HR 1.36, 95% C.I. 1.16-1.59, P < 0.001). CONCLUSIONS: Assessment of CFS is deeply affected by the underlying methodology, with the potential to profoundly affect decision-making. The CFS-MDT appears to be a weak alternative to conventional CFS. Standardisation of CFS use is of paramount importance in clinical and research practice in haemodialysis. TRIAL REGISTRATION: Clinicaltrials.gov : NCT03071107 registered 06/03/2017.

Ultrasound quadriceps muscle thickness is variably associated with frailty in haemodialysis recipients.

BACKGROUND: Ultrasonographic quantitation of quadriceps muscle mass is increasingly used for assessment of sarcopenia, but its relationship with frailty in haemodialysis recipients is not known. This study explores the relationship between ultrasound-derived bilateral anterior thigh thickness (BATT), sarcopenia, and frailty by common frailty tools (Frailty Phenotype [FP], Frailty Index [FI], Edmonton Frailty [EFS], and Clinical Frailty Scale [CFS]). METHODS: This was an exploratory analysis of a subgroup of adult prevalent (≥3 months) haemodialysis recipients deeply phenotyped for frailty. Ultrasound assessment of BATT was obtained with participants at an angle of ≤45°, with legs outstretched and knees resting at 10°-20°, according to an established protocol. Associations with frailty were explored via both linear and logistic regressions for BATT, Low Muscle Mass (LMM), and sarcopenia with stepwise adjustment for a priori covariables. RESULTS: In total 223 study participants had ultrasound measurements. Frailty ranged from 34% for FP to 58% for FI. BATT was associated with increasing frailty on simple linear regression by all frailty tools, but lost significance on addition of covariables. Upon dichotomising frailty tools into Frail/Not Frail, BATT was associated with frailty by all tools on univariable analyses, but only retained association for EFS on the fully adjusted model (OR 0.97, 95% C.I. 0.94-1.00, P = 0.05). CONCLUSIONS: Ultrasound measures of quadriceps thickness is variably associated with frailty in prevalent haemodialysis recipients, dependent upon the frailty tool used, but not independent of other variables. Further work is required to establish the added value of sarcopenia measurement in frail haemodialysis patients. TRIAL REGISTRATION: Clinicaltrials.gov : NCT03071107 registered 06/03/2017.

Early Experience With the Bentley BeGraft Aortic Stent for the Management of Aortic Arch Pathology in the Paediatric Population.

BACKGROUND: Aortic arch pathology in older children is often treated preferentially with stenting. Both bare metal and covered stents have been utilised, with potential advantages of covered stents. The search for the ideal covered stent continues. METHODS: Retrospective review of all paediatric patients undergoing treatment of aortic arch pathology utilising the Bentley BeGraft Aortic stent (BeGraft Aortic, Bentley InnoMed, Hechingen, Germany) from June 2017 to May 2021. Outcome measures were procedural success, complications, medium-term patency and need for re-intervention. RESULTS: Fourteen (14) stents were placed in 12 children (seven males). Indications were coarctation of the aorta in 10 and aneurysm in two. Median age was 11.8 years (8.7-16.6 years) and median weight 42.5 kg (24.8-84 kg). Median coarctation narrowing of 4 mm (range 1-9 mm), improved to 11 mm (range 9-15 mm). The median coarctation gradient improved from 32 mmHg (range 11-42 mmHg) to 7 mmHg (range 0-14 mmHg). Both aneurysms were successfully occluded. There was no mortality or major morbidity. In one patient balloon rupture occurred requiring a second balloon for full inflation and one patient had a minor access site bleed. Follow-up median was 28 months (range 13-65 months). One patient underwent repeat balloon dilation for increased blood pressure gradient at 47 months post implant and a second patient additional stent insertion for a mid-stent aneurysm at 65 months. CONCLUSION: The Bentley BeGraft Aortic stent can be safely deployed in children for the treatment of aortic arch pathology. Medium-term patency is acceptable. Longer term follow-up in larger series will be required to assess stent performance.

Treatment guideline concordance, initiation, and abandonment in patients with non-metastatic breast cancer from the African Breast Cancer-Disparities in Outcomes (ABC-DO) cohort in sub-Saharan Africa: a prospective cohort study.

BACKGROUND: Comprehensive breast cancer management is essential to achieve high breast cancer survival; however, detailed reports of the treatment regimens received by patients are scarce in sub-Saharan Africa where survival is low. We aimed to examine treatment initiation, guideline concordance, and abandonment in patients with non-metastatic breast cancer in sub-Saharan Africa from the African Breast Cancer-Disparities in Outcomes (ABC-DO) prospective cohort. METHODS: The ABC-DO prospective cohort study recruited women (aged ≥18 years) with newly diagnosed invasive breast cancer in eight hospitals across five sub-Saharan African countries (Namibia, Nigeria, Uganda, South Africa, and Zambia). We analysed treatments received by women who were classified as non-metastatic (M0) at the initial presentation. Data on surgery, radiotherapy, and systemic therapies were obtained from medical records and a self-reported follow-up questionnaire at 6 months after the diagnosis, follow-up calls every 3 months, and a baseline questionnaire. Initiation, completion, and abandonment of treatment modalities and combined therapy regimens were examined overall, by country-specific groups, and by clinical factors relevant for guideline-based treatment. FINDINGS: Of 2313 women recruited into the ABC-DO study between Sept 10, 2014, and Dec 31, 2017, 2226 had histologically or clinically confirmed breast cancer. Of these 2226 women, 510 were excluded from the present analysis because 378 had metastatic disease, 37 were prevalent cases (defined as those previously diagnosed with breast cancer >2 years before baseline), 82 had unknown TNM stage, and 13 were White or Asian women in South Africa (number was too small for analysis). After a median follow-up of 5·2 years (IQR 4·6-5·9), 1163 (68%) of 1716 women underwent breast cancer surgery. Surgery and systemic therapy (ie, multimodality treatment) with radiotherapy was initiated in 370 (36%) of 1028 women with localised tumours versus 156 (23%) of 688 women with locally advanced tumours, whereas multimodality treatment without radiotherapy was initiated in 386 (38%) versus 167 (24%) women, respectively. Of 1530 patients requiring chemotherapy (which excludes 105 who died within 6 months after baseline), 1013 (66%) initiated treatment of neoadjuvant chemotherapy or surgery within 3 months after baseline, which was adequately completed by 359 (35%) of 1013 women, marginally completed by 284 (28%), abandoned by 200 (20%), and unknown in 151 (15%). 19 (2%) women died within 6 months after chemotherapy initiation. Of 1375 women in whom endocrine therapy was indicated, this treatment was initiated in 920, and lasted at least 3 years in 367 (40%) women. Treatment disparities between country-specific groups were substantial for all therapy regimens. INTERPRETATION: A high proportion of patients with non-metastatic breast cancer did not initiate, did not fully complete, or abandoned treatment with surgery, systemic therapy, radiotherapy, or an appropriate combination of these, highlighting the need for improved treatment access and completion in sub-Saharan Africa to potentially prevent premature breast cancer deaths. FUNDING: National Institutes of Health (National Cancer Institute), Susan G Komen, and the International Agency for Research on Cancer.

Cancer in sub-Saharan Africa: a Lancet Oncology Commission.

In sub-Saharan Africa (SSA), urgent action is needed to curb a growing crisis in cancer incidence and mortality. Without rapid interventions, data estimates show a major increase in cancer mortality from 520 348 in 2020 to about 1 million deaths per year by 2030. Here, we detail the state of cancer in SSA, recommend key actions on the basis of analysis, and highlight case studies and successful models that can be emulated, adapted, or improved across the region to reduce the growing cancer crises. Recommended actions begin with the need to develop or update national cancer control plans in each country. Plans must include childhood cancer plans, managing comorbidities such as HIV and malnutrition, a reliable and predictable supply of medication, and the provision of psychosocial, supportive, and palliative care. Plans should also engage traditional, complementary, and alternative medical practices employed by more than 80% of SSA populations and pathways to reduce missed diagnoses and late referrals. More substantial investment is needed in developing cancer registries and cancer diagnostics for core cancer tests. We show that investments in, and increased adoption of, some approaches used during the COVID-19 pandemic, such as hypofractionated radiotherapy and telehealth, can substantially increase access to cancer care in Africa, accelerate cancer prevention and control efforts, increase survival, and save billions of US dollars over the next decade. The involvement of African First Ladies in cancer prevention efforts represents one practical approach that should be amplified across SSA. Moreover, investments in workforce training are crucial to prevent millions of avoidable deaths by 2030. We present a framework that can be used to strategically plan cancer research enhancement in SSA, with investments in research that can produce a return on investment and help drive policy and effective collaborations. Expansion of universal health coverage to incorporate cancer into essential benefits packages is also vital. Implementation of the recommended actions in this Commission will be crucial for reducing the growing cancer crises in SSA and achieving political commitments to the UN Sustainable Development Goals to reduce premature mortality from non-communicable diseases by a third by 2030.

A population cohort analysis of English transplant centers indicates major adverse cardiovascular events after kidney transplantation.

Major adverse cardiovascular event (MACE) rates immediately after kidney transplantation remain uncertain due to heterogeneous reporting in the literature. To clarify this, we retrospectively studied every eligible kidney transplant procedure performed in England between April 1, 2002 and March 31, 2018, with follow-up through August 31, 2019. The primary outcome of interest was MACE broadly defined as any hospital admission with myocardial infarction, stroke, unstable angina, heart failure, any coronary revascularisation procedure and/or any cardiovascular death. Among 30,325 kidney transplant recipients, MACE occurred in 781 within the first year after transplantation (2.6% of all kidney transplant procedures). Of these 781 events, 201 occurred during the index admission for kidney transplantation surgery representing 25.7% of all first-year MACE and 0.7% of all kidney transplant procedures. Kidney transplant recipients who suffered a non-fatal MACE within the first year had significantly decreased 1-, 3-, 5- and 10-year patient survival of 80.5%, 70.2%, 59.5% and 38.6% respectively, compared to 97.4%, 94.4%, 90.7% and 78.4% for kidney transplant recipients not developing MACE. In an adjusted Cox proportional hazard model, non-fatal MACE within the first-year post-transplant was associated with significant long-term mortality risk (hazard ratio 2.59; 95% confidence interval 2.34-2.88). Kidney transplant recipients experiencing MACE during the index admission compared to subsequent admissions were differentiated by age, sex and previous cardiac history but had similar patient survival. These rates are significantly lower than those reported in North America. Thus, our data confirm MACE is not a benign post-transplant event and has a strong association with long-term mortality risk.

International perspectives on the development, application, and evaluation of a multicancer early detection strategy.

The development and implementation of a multicancer early detection (MCED) test that is effective and affordable has the potential to change cancer care systems around the world. However, careful consideration is needed within the context of different health care settings (both low- and middle-income countries and high-income countries) to roll out an MCED test and promote equity in access.

Monitoring sub-surface chemical reactions in heterogeneous materials using wavefront-shaping-assisted bidirectional focusing.

We have developed a bidirectional focusing microscope that utilizes feedback-assisted wavefront shaping to focus light inside a heterogenous material in order to monitor sub-surface chemical reactions. The bidirectional geometry is found to provide superior intensity enhancement relative to single-sided focusing, owing to increased mode control and long-range mesoscopic correlations. Also, we demonstrate the microscope's capability to measure sub-surface chemical reactions by optically monitoring the photodegradation of a Eu-doped organic molecular crystal embedded in a heterogeneous material using both fluorescence and Raman spectroscopy as probe techniques.

NEDD4L-mediated Merlin ubiquitination facilitates Hippo pathway activation.

The tumor suppressor Merlin/NF2, a key activator of the Hippo pathway in growth control, is regulated by phosphorylation. However, it is uncertain whether additional post-translational modifications regulate Merlin. Here, we show that ubiquitination is required to activate Merlin in the Hippo pathway. Ubiquitinated Merlin is mostly conjugated by one or two ubiquitin molecules. Such modification is promoted by serine 518 dephosphorylation in response to Ca2+ signaling or cell detachment. Merlin ubiquitination is mediated by the E3 ubiquitin ligase, NEDD4L, which requires a scaffold protein, AMOTL1, to approach Merlin. Several NF2-patient-derived Merlin mutations disrupt its binding to AMOTL1 and its regulation by the AMOTL1-NEDD4L apparatus. Lysine (K) 396 is the major ubiquitin conjugation residue. Disruption of Merlin ubiquitination by the K396R mutation or NEDD4L depletion diminishes its binding to Lats1 and inhibits Lats1 activation. These effects are also accompanied by loss of Merlin's anti-mitogenic and tumor suppressive properties. Thus, we propose that dephosphorylation and ubiquitination compose an intramolecular relay to activate Merlin functions in activating the Hippo pathway during growth control.

Concreteness and levels of processing: a test of the dual-coding hypothesis using dynamic visual noise.

Concreteness and levels of processing (LOP) effects have been attributed to the differential availability of visual images for concrete words, and at deeper levels of processing, respectively. Interestingly, the concreteness effect has been shown to disappear under conditions involving dynamic visual noise (DVN), which is thought to suppress the generation of visual images from long-term memory. The present study further investigated the role of visual imagery in concreteness and LOP effects. Across four experiments, DVN was manipulated during study, and participants' memory for concrete and abstract words was measured using recall and recognition tests. Although some support for dual-coding was found, concreteness and LOP effects were not fully explained by visual imagery because they were present under DVN conditions. We conclude that concreteness and LOP effects may be better explained by an "extended dual-coding theory" that incorporates the role of context availability in accounting for this pattern of results.

Outcomes After Stage I Norwood Palliation in a Recently Established Program Can Achieve Results Similar to Longer Established Services.

BACKGROUND: Infants with hypoplastic left heart syndrome (HLHS) or similar single ventricle cardiac lesions require a three-stage surgical approach, the first step being the Stage I Norwood procedure. The Queensland Children's Hospital (QCH) in Australia is a tertiary hospital providing the only cardiac surgical service to children in Queensland and northern New South Wales. OBJECTIVE: To review the centre's outcomes of Norwood procedures performed in the last 6 years. MATERIALS AND METHODS: We retrospectively evaluated all infants undergoing the stage I Norwood procedure between January 2015 and August 2021. Mortality, intensive care length of stay, events of cardiac arrest following surgery and duration of mechanical ventilation were calculated and analysed for subgroups depending on type of pulmonary shunt type (right-ventricle-to-pulmonary-artery shunt [RVPAS] vs the modified Blalock-Taussig shunt [MBTS]). RESULTS: Forty-nine (49) patients were included. Overall survival to stage two operation (Glenn) was 90%. Both shunts were used evenly with the RVPA conduit preferred for HLHS and the MBTS largely chosen for hypoplastic left heart variants. In univariable analysis there was no difference in cardiac arrest or mortality rate for the patient with a RVPAS compared to the patient with a MBTS. CONCLUSION: We show that a recently established Norwood program can achieve results that are comparable to those reported by longer established centres, and the international literature.

Ten Years of Percutaneous Pulmonary Valve Implantation in Australia and New Zealand.

OBJECTIVE: This study sought to investigate the characteristics, morbidity (including the rate of infective endocarditis and valve replacement) and mortality of individuals undergoing percutaneous pulmonary valve implantation in Australia and New Zealand since the procedure has been performed. BACKGROUND: The outcomes of percutaneous pulmonary valve implantation in Australia and New Zealand have not been evaluated. Recent international data, including patients from New Zealand, suggests the rate of infective endocarditis is not insignificant. METHODS: A retrospective multi-site cohort study was undertaken via medical record review at the centres where percutaneous pulmonary valve implantation has been performed. All procedures performed from 2009-March 2018 were included. Individuals were identified from local institution databases. Data was collected and analysed including demographics, details at the time of intervention, haemodynamic outcome, post procedure morbidity and mortality. Multi-site ethics approval was obtained. RESULTS: One hundred and seventy-nine (179) patients attended the cardiac catheter laboratory for planned percutaneous pulmonary valve implantation. Of these patients, 172 underwent successful implantation. Tetralogy of Fallot and pulmonary atresia were the most common diagnoses. The median age at procedure was 19 years (range 3-60 yrs). There was a significant improvement in the acute haemodynamics in patients undergoing percutaneous pulmonary valve implantation for stenosis. Seven (7) patients (3.9%) experienced a major procedural/early post procedure complication (death, conversion to open procedure, cardiac arrest), including two deaths. The annualised rates of infective endocarditis and valve replacement were 4.6% and 3.8% respectively. There was one death related to infective endocarditis in follow-up. CONCLUSIONS: Percutaneous pulmonary valve replacement is a relatively safe method of rehabilitating the right ventricular outflow tract.

National health system characteristics, breast cancer stage at diagnosis, and breast cancer mortality: a population-based analysis.

BACKGROUND: In some countries, breast cancer age-standardised mortality rates have decreased by 2-4% per year since the 1990s, but others have yet to achieve this outcome. In this study, we aimed to characterise the associations between national health system characteristics and breast cancer age-standardised mortality rate, and the degree of breast cancer downstaging correlating with national age-standardised mortality rate reductions. METHODS: In this population-based study, national age-standardised mortality rate estimates for women aged 69 years or younger obtained from GLOBOCAN 2020 were correlated with a broad panel of standardised national health system data as reported in the WHO Cancer Country Profiles 2020. These health system characteristics include health expenditure, the Universal Health Coverage Service Coverage Index (UHC Index), dedicated funding for early detection programmes, breast cancer early detection guidelines, referral systems, cancer plans, number of dedicated public and private cancer centres per 10 000 patients with cancer, and pathology services. We tested for differences between continuous variables using the non-parametric Kruskal-Wallis test, and for categorical variables using the Pearson χ2 test. Simple and multiple linear regression analyses were fitted to identify associations between health system characteristics and age-standardised breast cancer mortality rates. Data on TNM stage at diagnosis were obtained from national or subnational cancer registries, supplemented by a literature review of PubMed from 2010 to 2020. Mortality trends from 1950 to 2016 were assessed using the WHO Cancer Mortality Database. The threshold for significance was set at a p value of 0·05 or less. FINDINGS: 148 countries had complete health system data. The following variables were significantly higher in high-income countries than in low-income countries in unadjusted analyses: health expenditure (p=0·0002), UHC Index (p<0·0001), dedicated funding for early detection programmes (p=0·0020), breast cancer early detection guidelines (p<0·0001), breast cancer referral systems (p=0·0030), national cancer plans (p=0·014), cervical cancer early detection programmes (p=0·0010), number of dedicated public (p<0·0001) and private (p=0·027) cancer centres per 10 000 patients with cancer, and pathology services (p<0·0001). In adjusted multivariable regression analyses in 141 countries, two health system characteristics were significantly associated with lower age-standardised mortality rates: higher UHC Index levels (ß=-0·12, 95% CI -0·16 to -0·08) and increasing numbers of public cancer centres (ß=-0·23, -0·36 to -0·10). These findings indicate that each unit increase in the UHC Index was associated with a 0·12-unit decline in age-standardised mortality rates, and each additional public cancer centre per 10 000 patients with cancer was associated with a 0·23-unit decline in age-standardised mortality rate. Among 35 countries with available breast cancer TNM staging data, all 20 that achieved sustained mean reductions in age-standardised mortality rate of 2% or more per year for at least 3 consecutive years since 1990 had at least 60% of patients with invasive breast cancer presenting as stage I or II disease. Some countries achieved this reduction without most women having access to population-based mammographic screening. INTERPRETATION: Countries with low breast cancer mortality rates are characterised by increased levels of coverage of essential health services and higher numbers of public cancer centres. Among countries achieving sustained mortality reductions, the majority of breast cancers are diagnosed at an early stage, reinforcing the value of clinical early diagnosis programmes for improving breast cancer outcomes. FUNDING: None.