Search

Background The coronavirus disease 2019 (COVID-19) pandemic impacted cancer services worldwide. We examined the effect of the first three pandemic waves on the number of electronic (e)-referrals to rapid access clinics (RACs) for breast, lung and prostate cancer in Ireland. Methods This study used a retrospective, repeated cross-sectional design. The predicted weekly number of e-referrals by suspected cancer types from March 2020 to May 2021 was calculated using the Holt-Winters seasonal smoothing method, based on the observed numbers from a representative pre-pandemic period (01 January 2019 to 01 March 2020) and compared this with the observed number across the first three pandemic waves (02 March 2020 to 09 May 2021). Percentage differences were calculated between observed and predicted numbers of e-referrals for the three RACs and patterns were examined in each wave. Results Observed e-referrals were lower than predicted for all three RACs in the first wave of the pandemic (15.7% lower for breast, 39.5% lower for lung and 28.1% lower for prostate) with varying levels of recovery in the second and third waves for the three e-referral types. Conclusions The COVID-19 pandemic impacted patterns of e-referrals to RACs in the first three pandemic waves in Ireland. Early identification of changes in engagement with health services, such as a decrease in primary care presentations with a resultant decrease in e-referrals to RACs can allow for a rapid response from cancer control programmes. Continued surveillance of the impact of service disruption on cancer services allows policy makers and strategic leaders in cancer control programmes to respond rapidly to mitigate the impact on cancer outcomes. [ABSTRACT FROM AUTHOR]

Objective: Many population-based breast screening programmes temporarily suspended routine screening following the COVID-19 pandemic onset. This study aimed to describe screening mammography utilisation and the pattern of screen-detected breast cancer diagnoses following COVID-19-related screening disruptions in Ireland. Methods: Using anonymous aggregate data from women invited for routine screening, three time periods were examined: (1) January–December 2019, (2) January–December 2020, and (3) January–December 2021. Descriptive statistics were conducted and comparisons between groups were performed using chi-square tests. Results: In 2020, screening mammography capacity fell by 67.1% compared to 2019; recovering to 75% of mammograms performed in 2019, during 2021. Compared to 2019, for screen-detected invasive breast cancers, a reduction in Grade 1 (14.2% vs. 17.2%) and Grade 2 tumours (53.4% vs. 58.0%) and an increase in Grade 3 tumours (32.4% vs. 24.8%) was observed in 2020 (p = 0.03); whereas an increase in Grade 2 tumours (63.3% vs. 58.0%) and a reduction in Grade 3 tumours (19.6% vs. 24.8%) was found in 2021 (p = 0.02). No changes in oestrogen receptor-positive or nodal-positive diagnoses were observed; however the proportion of oestrogen/progesterone receptor-positive breast cancers significantly increased in 2020 (76.2%; p < 0.01) and 2021 (78.7%; p < 0.001) compared to 2019 (67.8%). Conclusion: These findings demonstrate signs of a grade change for screen-detected invasive breast cancers early in the pandemic, with recovery evident in 2021, and without an increase in nodal positivity. Future studies are needed to determine the COVID-19 impact on long-term breast cancer outcomes including mortality. [ABSTRACT FROM AUTHOR]

The combination of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) can be associated with significant toxicity. We performed a systematic review and meta-analysis of the toxicity of combination treatment of ICIs with TKIs (ICI + TKI) in clinical trials with solid organ malignancies. Our primary endpoint explored the incidence of grade 3 - 5 (G3-5) treatment-related toxicity and our secondary endpoints included the incidence of toxicity by treatment type, disease type and studies with run-in strategies. A total of 9750 abstracts were identified, of which 72 eligible studies were included. The most common disease types were non-small cell lung cancer (n=8, 11.1%), renal cell carcinoma (n=10, 13.8%) and hepatobiliary cancers (n=10, 13.8%). The overall incidence of G3-5 toxicity was 56% (95% CI = 50% -- 61%). The most common TKIs combined with ICIs in this analysis were multi-targeted TKIs (n = 52, 72%), VEGF specific (n = 9, 12.5%), or oncogene-targeting TKIs (EGFR, ALK, BRAF, MEK) (n =11, 15.3%). Oncogene-targeted TKIs were associated a higher incidence of rashes and immune related adverse events (irAEs) and lower incidence of hypertension. In studies which used a TKI 'run-in' to mitigate toxicity, the pooled estimate of G3-5 toxicity was 71% (95% CI 57-81%). Almost half of studies (48%) omitted the incidence of G3-5 irAEs. Our work suggests that the majority of patients who receive ICI-TKI combinations will experience high grade toxicity (G3-G5) and that toxicity may be specific to TKI partner (Oncogene targeted TKIs: Rash, irAEs; VEGF/Multitargeted: Hypertension). These data did not suggest that a TKI 'run-in' was associated with a lower incidence of G3-5 toxicity. Reporting of irAEs was inconsistent supporting the need for harmonisation of adverse event reporting to include onset, duration and treatment. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a global health priority. In addition to being the leading cause of trauma related death, TBI can result in long-term disability and loss of health. Disorders of haemostasis are common despite the absence of some of the traditional risk factors for coagulopathy following trauma. Similar to trauma induced coagulopathy, this manifests with a biphasic response consisting of an early hypocoagulable phase and delayed hypercoagulable state. This coagulopathy is clinically significant and associated with increased rates of haemorrhagic expansion, disability and death. The pathophysiology of TBI-induced coagulopathy is complex but there is biologic plausibility and emerging evidence to suggest that extracellular vesicles (EVs) have a role to play. TBI and damage to the blood brain barrier result in release of brain-derived EVs that contain tissue factor and phosphatidylserine on their surface. This provides a platform on which coagulation can occur. Preclinical animal models have shown that an early rapid release of EVs results in overwhelming activation of coagulation resulting in a consumptive coagulopathy. This phenomenon can be attenuated with administration of substances to promote EV clearance and block their effects. Small clinical studies have demonstrated elevated levels of procoagulant EVs in patients with TBI correlating with clinical outcome. EVs represent a promising opportunity for use as minimally invasive biomarkers and potential therapeutic targets for TBI patients. However, additional research is necessary to bridge the gap between their potential and practical application in clinical settings. [ABSTRACT FROM AUTHOR]

Aims: The aims of this study were to estimate potentially clinically important drug–drug interaction (DDI) prevalence, and the average causal effect of DDI exposure on adverse drug reaction (ADR)‐related hospital admission, and to examine differences in health‐related quality of life (HRQoL) and length of stay (LOS) per DDI exposure in an older (≥65 years) population acutely hospitalized. Methods: This was a cross‐sectional study conducted among 798 older individuals acutely admitted to hospital in Ireland between 2016 and 2017. Medication (current/recently discontinued/over‐the‐counter) and clinical data (e.g., creatinine clearance) were available. DDIs were identified using the British National Formulary (BNF) and Stockley's Drug Interactions. Causal inference models for DDI exposure on ADR‐related hospital admission were developed using directed acyclic graphs. Multivariable logistic regression was used to estimate the average causal effect. Differences in HRQoL (EQ‐5D) and LOS per DDI exposure were examined non‐parametrically. DDI prevalence, adjusted odds ratios (aOR), and 95% confidence intervals (CIs) are reported. Results: A total of 782 (98.0%) individuals using two or more drugs were included. Mean age was 80.9 (SD ± 7.5) years (range: 66–105); 52.2% were female; and 45.1% (n = 353) had an ADR‐related admission. At admission, 316 (40.4% [95% CI: 37.0–43.9]) patients had at least one DDI. The average causal effect of DDI exposure on ADR‐related hospital admission was aOR = 1.21 [95% CI: 0.89–1.64]. This was significantly increased by exposure to: DDIs which increase bleeding risk (aOR = 2.00 [1.26–3.12]); aspirin‐warfarin (aOR = 2.78 [1.37–5.65]); and esomeprazole‐escitalopram (aOR = 3.22 [1.13–10.25]. DDI‐exposed patients had lower HRQoL (mean EQ‐5D = 0.49 [±0.39]) compared those non‐DDI‐exposed (mean EQ‐5D = 0.57 [±0.41]), (P =.03); and greater median LOS in hospital (8 [IQR5–16]days) compared those non‐DDI‐exposed (7 [IQR 4–14] days),(P =.04). Conclusions: Potentially clinically important DDIs carry an increased average causal effect on ADR‐related admission, significantly (two‐fold) by exposure to DDIs that increase bleeding risk, which should be targeted for medicine optimization. [ABSTRACT FROM AUTHOR]

Purpose: Cancer survivors can experience symptoms such as fatigue, pain and distress that persist for many months following treatment. These enduring symptoms often impact on participation in self-care activities, returning to school and/or work, and leisure and social activities. Self-management support is increasingly recognised as a core aspect of cancer survivorship care to reduce the impact of persistent symptoms. The purpose of this study was to examine the feasibility and potential effectiveness of a group-based self-management intervention, OptiMal, to improve the physical and psychological health of cancer survivors. OptiMal is a six-week intervention comprising weekly sessions on fatigue, stress and physical activity, diet and effective communication strategies. Methods: A feasibility randomised control trial was undertaken. Individuals up to two years after cancer treatment were randomised to OptiMal or usual care. Feasibility was examined through recruitment and retention metrics. Potential effectiveness was tested through patient-reported outcomes collected at baseline and three months post-intervention. Descriptive and inferential statistics were used to analyse study data. Results: Recruitment for this study was 32.5% (80/246 eligible individuals) with 77.5% retention at three-month follow-up (82.5% for intervention group and 72.5% for control group). Of those who attended the intervention, 19 (73%) attended all OptiMal sessions, indicating high adherence to the intervention. The majority of participants had breast cancer and were between 12 and 24 months post-treatment. The intervention group (n = 29) had statistically significant greater improvements in anxiety (p = 0.04) and health-related quality of life (health index score: p = 0.023, visual analogue score: p = 0.035) at three months post-intervention than the control group. Conclusions: Recruitment and retention in this study was similar to other cancer trials and the high adherence rate indicates that OptiMal is an acceptable self-management intervention for cancer survivors and warrants further investigation. OptiMal is intended to address symptoms reported across different cancer types. However, a limitation of this study was that the majority of participants had breast cancer, and therefore, generalisability of findings cannot be assumed for other cancer types. Future studies of OptiMal therefore need to use different strategies to recruit survivors of other cancer types. [ABSTRACT FROM AUTHOR]