Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Comparison of anti-thrombotic strategies using Bivalirudin, Heparin plus Glycoprotein IIb/IIIa inhibitors and Unfractionated Heparin Monotherapy for patients undergoing percutaneous coronary intervention – A single centre observational study

Aims: The study was planned to compare Anti-thrombotic strategies for patients undergoing PCI in a real world population with an emphasis on occurrence of major bleeding, composite ischemic end points and economic outcomes. Methods: The present study is a single center, prospective, observational study in consecutive patients undergoing PCI at Fortis Escorts Heart Institute (FEHI) and describes Authors' experience with three different Anti-Thrombotic Strategies in a real world population. Patients were consecutively enrolled in the study and the choice of Anti-thrombotic strategy was left to individual operator(s) based on their own clinical judgment and patient's affordability. No specific inclusion/exclusion criteria were specified on the choice of Anti-Thrombotic Strategy. Results: A total 1453 patients were consecutively enrolled into the study and were followed telephonically after 30 days. 252 patients were treated with Bivalirudin (Angiomax) during PCI (17.3%), 430 (29.6%) patients were treated with Heparin plus GPI & remaining 771 (53.1%) were treated with Heparin monotherapy. Incidence of major bleeding was lowest in patients treated with Bivalirudin (1.59%) when compared to Heparin plus GPI (3.49%) and Heparin monotherapy (5.97%), p = 0.005 Bivalirudin vs. Heparin Monotherapy, and p = 0.145, Bivalirudin vs. Heparin + GPI. No bleeding was observed in STEMI patients treated with Bivalirudin compared to 7.4% in patients treated with GPI and 14.3% in patients treated with UFH. Similarly non-access site bleeding was lowest in patients treated with Bivalirudin. Only 4 patients (1.6%) treated with Bivalirudin required Blood transfusion compared to 25 in Heparin plus GPI (5.8%) and 38 (5%) in Heparin Monotherapy arm. In Composite Ischemic end-points, no “All-cause Mortality” was observed in Bivalirudin group compared to 2.8% in Heparin plus GPI. Early stent thrombosis was seen in 1 patient with Heparin plus GPI and none with Heparin monotherapy and Bivalirudin group. None of the patients underwent TLR (target lesion revascularization) and TVR (target vessel revascularization) within 30 days post procedure other than one early stent thrombosis reported with Heparin plus GPI. Cost of blood product transfusion was lower with Bivalirudin as compared to Heparin plus GP IIb/IIIa arm (p = 0.01) and with Heparin alone (p = 0.001). Due to lower complications including blood transfusions and reduced hospital stay in Bivalirudin group, these benefits outweigh the incremental cost due to higher acquisition cost of the drug. Conclusion: Bivalirudin use during PCI is associated with a distinct advantage of having lower access site and non-access site bleeding without compromising on the efficacy. We observed a reduction in blood transfusions, hospital stay and mortality for patients treated with Bivalirudin compared with Heparin plus GPI or Heparin Monotherapy. Bivalirudin can be safely adopted into our Institutional protocol for the treatment of high risk PCI such as STEMI, ACS, and Complex elective PCI

SARS-CoV-2 Reinfection Rate and Estimated Effectiveness of the Inactivated Whole Virion Vaccine BBV152 Against Reinfection Among Health Care Workers in New Delhi, India

A surge of COVID-19 occurred from March to June 2021, in New Delhi, India, linked to the B.1.617.2 (Delta) variant of SARS-CoV-2. COVID-19 vaccines were rolled out for health care workers (HCWs) starting in January 2021. To assess the incidence density of reinfection among a cohort of HCWs and estimate the effectiveness of the inactivated whole virion vaccine BBV152 against reinfection. This was a retrospective cohort study among HCWs working at a tertiary care center in New Delhi, India. Vaccination with 0, 1, or 2 doses of BBV152. The HCWs were categorized as fully vaccinated (with 2 doses and ≥15 days after the second dose), partially vaccinated (with 1 dose or 2 doses with <15 days after the second dose), or unvaccinated. The incidence density of COVID-19 reinfection per 100 person-years was computed, and events from March 3, 2020, to June 18, 2021, were included for analysis. Unadjusted and adjusted hazard ratios (HRs) were estimated using a Cox proportional hazards model. Estimated vaccine effectiveness (1 - adjusted HR) was reported. Among 15 244 HCWs who participated in the study, 4978 (32.7%) were diagnosed with COVID-19. The mean (SD) age was 36.6 (10.3) years, and 55.0% were male. The reinfection incidence density was 7.26 (95% CI: 6.09-8.66) per 100 person-years (124 HCWs [2.5%], total person follow-up period of 1696 person-years as time at risk). Fully vaccinated HCWs had lower risk of reinfection (HR, 0.14 [95% CI, 0.08-0.23]), symptomatic reinfection (HR, 0.13 [95% CI, 0.07-0.24]), and asymptomatic reinfection (HR, 0.16 [95% CI, 0.05-0.53]) compared with unvaccinated HCWs. Accordingly, among the 3 vaccine categories, reinfection was observed in 60 of 472 (12.7%) of unvaccinated (incidence density, 18.05 per 100 person-years; 95% CI, 14.02-23.25), 39 of 356 (11.0%) of partially vaccinated (incidence density 15.62 per 100 person-years; 95% CI, 11.42-21.38), and 17 of 1089 (1.6%) fully vaccinated (incidence density 2.18 per 100 person-years; 95% CI, 1.35-3.51) HCWs. The estimated effectiveness of BBV152 against reinfection was 86% (95% CI, 77%-92%); symptomatic reinfection, 87% (95% CI, 76%-93%); and asymptomatic reinfection, 84% (95% CI, 47%-95%) among fully vaccinated HCWs. Partial vaccination was not associated with reduced risk of reinfection. These findings suggest that BBV152 was associated with protection against both symptomatic and asymptomatic reinfection in HCWs after a complete vaccination schedule, when the predominant circulating variant was B.1.617.2