Impact of COVID-19 on routine childhood immunisations in low- and middle-income countries: A scoping review.

Routine vaccines are critical to child health. The COVID-19 pandemic significantly impacted essential health services, particularly in low-and middle-income countries (LMICs). We reviewed literature to determine the impact of COVID-19 on service delivery and uptake of routine childhood immunisation in LMICs. We reviewed papers published between March 2020 and June 2022 using a scoping review framework, and assessed each paper across the World Health Organisation health system strengthening framework. Our search identified 3,471 publications; 58 studies were included. One-quarter of studies showed routine childhood immunisation coverage declined (10% to 38%) between 2019 to 2021. Declines in the number of vaccine doses administered (25% to 51%), timeliness (6.2% to 34%), and the availability of fixed and outreach services were also reported. Strategies proposed to improve coverage included catch-up activities, strengthening supply chain and outreach services. Re-focusing efforts on increasing coverage is critical to improve child health and reduce the likelihood of disease outbreaks.

Feasibility of a multiparametric MRI protocol for imaging biomarkers associated with neoadjuvant radiotherapy for soft tissue sarcoma.

Objective: Soft tissue sarcoma (STS) is a rare malignancy with a 5 year overall survival rate of 55%. Neoadjuvant radiotherapy is commonly used in preparation for surgery, but methods to assess early response are lacking despite pathological response at surgery being predictive of overall survival, local recurrence and distant metastasis. Multiparametric MR imaging (mpMRI) is used to assess response in a variety of tumours but lacks a robust, standardised method. The overall aim of this study was to develop a feasible imaging protocol to identify imaging biomarkers for further investigation. Methods: 15 patients with biopsy-confirmed STS suitable for pre-operative radiotherapy and radical surgery were imaged throughout treatment. The mpMRI protocol included anatomical, diffusion-weighted and dynamic contrast-enhanced imaging, giving estimates of apparent diffusion coefficient (ADC) and the area under the enhancement curve at 60 s (iAUC60). Histological analysis of resected tumours included detection of CD31, Ki67, hypoxia inducible factor and calculation of a hypoxia score. Results: There was a significant reduction in T1 at visit 2 and in ADC at visit 3. Significant associations were found between hypoxia and pre-treatment iAUC60, pre-treatment ADC and mid-treatment iAUC60. There was also statistically significant association between mid-treatment ADC and Ki67. Conclusion: This work showed that mpMRI throughout treatment is feasible in patients with STS having neoadjuvant radiotherapy. The relationships between imaging parameters, tissue biomarkers and clinical outcomes warrant further investigation. Advances in knowledge: mpMRI-based biomarkers have good correlation with STS tumour biology and are potentially of use for evaluation of radiotherapy response.

Assessing the costs of historical inaction on climate change.

We consider alternative history scenarios in which explicit climate mitigation begins before the present day, estimating the total costs to date of delayed action. Considering a 2(1.5) degree Celsius stabilization target, peak costs are greater and reached sooner with a later start to mitigation, reaching 15(17)% of global GDP in 2085(2070) for a 1990 start and 18(35)% in 2080(2035) for a 2020 start. Further mitigation delay costs a best estimate of an additional 0.5(5) trillion dollars per year. Additional simulations show how optimal mitigation pathways evolve without imposing a warming limit, finding that median abatement levels and costs are not strongly dependent on start date. However, whereas 18(5) percent of optimal solutions starting in 1980 meet the 2(or 1.5) degree target, 5(or 0)% of 2020 simulations meet the goals. Discounted damages due to delayed mitigation action rise by 0.6 trillion US dollars per year in 2020.

Informing Future Risks of Record-Level Rainfall in the United States.

The changing risk of extreme precipitation is difficult to project. Events are rare by definition, and return periods of heavy precipitation events are often calculated assuming a stationary climate. Furthermore, ensembles of climate model projections are not large enough to fully categorize the tails of the distribution. To address this, we cluster the contiguous United States into self-similar hydroclimates to estimate changes in the expected frequency of extremely rare events under scenarios of global mean temperature change. We find that, although there is some regional variation, record events are projected in general to become more intense, with 500-year events intensifying by 10-50% under 2 °C of warming and by 40-100% under 4 °C of warming. This analysis could provide information to inform regional prioritization of resources to improve the resilience of U.S. infrastructure.

Precipitation variability increases in a warmer climate.

Understanding changes in precipitation variability is essential for a complete explanation of the hydrologic cycle's response to warming and its impacts. While changes in mean and extreme precipitation have been studied intensively, precipitation variability has received less attention, despite its theoretical and practical importance. Here, we show that precipitation variability in most climate models increases over a majority of global land area in response to warming (66% of land has a robust increase in variability of seasonal-mean precipitation). Comparing recent decades to RCP8.5 projections for the end of the 21st century, we find that in the global, multi-model mean, precipitation variability increases 3-4% K-1 globally, 4-5% K-1 over land and 2-4% K-1 over ocean, and is remarkably robust on a range of timescales from daily to decadal. Precipitation variability increases by at least as much as mean precipitation and less than moisture and extreme precipitation for most models, regions, and timescales. We interpret this as being related to an increase in moisture which is partially mitigated by weakening circulation. We show that changes in observed daily variability in station data are consistent with increased variability.

Tolerability of Concurrent Chemoradiation Therapy With Gemcitabine (GemX), With and Without Prior Neoadjuvant Chemotherapy, in Muscle Invasive Bladder Cancer.

PURPOSE: The aim of this study is to assess the tolerability of concurrent chemoradiation therapy with gemcitabine (GemX) in muscle invasive bladder cancer following neoadjuvant chemotherapy (neoGemX) by use of patient- and provider-reported outcomes. METHODS AND MATERIALS: Seventy-eight patients were treated with GemX. Thirty-eight received prior neoadjuvant chemotherapy (NAC). Patients were prospectively assessed during treatment and at 6 weeks and 12 months after treatment completion. Radiation therapy was given to a total dose of 52.5 Gy in 20 fractions with weekly concurrent gemcitabine chemotherapy, 100 mg/m2. Toxicity was assessed by the care provider and by a patient-reported outcome questionnaire collecting scores on the late effects in normal tissues-subjective, objective, management, and analytic scales and was statistically compared at baseline and 12 months, as well as between the neoGemX and GemX groups. RESULTS: The median duration of follow-up was 15.9 months. The radiation therapy completion rate was 95%, and 96% of patients completed at least 3 cycles of gemcitabine. Bowel toxicity of grade 3 or greater was reported in 7 of 38 patients (18%) in the neoGemX group and 5 of 25 (20%) in the GemX group. Three GemX and two neoGemX patients had grade 3 or greater urinary toxicity. Forty-nine patients completed questionnaires and were included in the analysis. Scores on the late effects in normal tissues-subjective, objective, management, and analytic scales showed an expected peak by week 4 of treatment. There was no statistically significant difference between mean scores at baseline and 12 months after treatment completion or between the neoGemX and GemX groups. CONCLUSIONS: This study demonstrates that GemX, alone or following NAC, has manageable toxicity and acceptable treatment completion rates. Allowing for small patient numbers and the nonrandomized nature of this study, these results do not suggest any additional toxicity from the use of NAC prior to GemX.

Using the Malthus programme to predict the recruitment of patients to MR-linac research trials in prostate and lung cancer.

In this study, we used evidence-based mathematical modelling to predict the patient cohort for MR-linac to assess its feasibility in a time of austerity. We discuss our results and the implications of evidence-based radiotherapy demand modelling tools such as Malthus on the implementation of new technology and value-based healthcare.

Prognostic Significance of CD44 and Orthopedia Homeobox Protein (OTP) Expression in Pulmonary Carcinoid Tumours.

CD44 and orthopedia homeobox protein (OTP) expressions have shown to be predictive of overall survival in pulmonary carcinoid (PC) tumours. The scope of the present study was to validate their role in PC patients and investigate potential application in clinical practice. Data was collected from patients presenting to a tertiary cancer centre diagnosed with PC between 2003 and 2015. Diagnosis was confirmed by central pathology review. Formalin-fixed paraffin-embedded (FFPE) tissue samples collected at diagnosis were scored using immunohistochemistry (H score) for standard CD44 and nuclear and cytoplasmic OTP protein expression. The study included 108 patients. High CD44/nuclear OTP (nOTP) expression was strongly associated with typical carcinoid (TC) histology (p < 0.001). Eighty-six patients, who underwent radical surgical resection, were selected to assess the impact of patient and tumour parameters on relapse-free survival (RFS). Sixty-nine (80 %) had TC and 17 (20 %) had atypical carcinoid tumours. On multivariate analysis, high CD44 and nOTP expression, TC histology and non-infiltrative tumour growth were associated with superior RFS. Early stage TC (stage pT1aN0) patients (N = 32; 46 %) had excellent prognosis irrespective of CD44/nOTP status. Importantly, TC patients with locally advanced disease (defined as >pT1aN0) and high CD44/nOTP expression (N = 26; 38 %) had excellent RFS (p = 0.005) compared to those with the same stage but low CD44 and/or nOTP (N = 11; 16 %). Additionally, the combination of CD44/nOTP expression and tumour growth pattern led to a more accurate prognostic system compared to the established WHO classification of PC tumours (concordance index = 0.902 vs 0.811, respectively, p < 0.001). Assessment of CD44/nOTP expression combined with tumour growth pattern identifies clear groups with largely different prognosis. These findings provide important information on how patients with these resected cancers should be followed up.