Impact of the Covid-19 Pandemic on Delivery of Acute and Post-Acute Care to Patients with Newly Diagnosed Traumatic Spinal Cord Injury.

Aim To investigate the impact of the first wave of the Covid-19 pandemic on the care of patients with newly acquired traumatic spinal cord injury (TSCI) in Ireland Methods A prospective audit of patients with newly acquired TSCI from 1st March to 30th June 2020 was undertaken. Cases were drawn from referrals received through the National Spinal Injuries Unit (NSIU) and neurosciences centres. The standard of care guidelines used were from National Health Service (NHS) England standards, the Irish Integrated Care Pathway and British Association of Spinal cord Injury Specialist (BASCIS) COVID-19 guidelines. Results Nineteen patients sustained a TSCI during the study period. Thirteen patients (68%) were treated in the NSIU, eleven of whom were subsequently repatriated to non-specialist centres. Twelve patients (63%) waited an average of 113.8 ± 33.4 days for admission to specialist in-patient rehabilitation. Nine patients (75%) had developed at least one secondary complication by the time of admission. Conclusion With the exception of waiting time for specialist in-patient rehabilitation, delivery of TSCI care during this period was similar to the care previously recorded. Shortcomings in service provision are long-standing and highlight the need for timely implementation of an integrated trauma network for Ireland.

Value of a 21-gene expression assay on core biopsy to predict neoadjuvant chemotherapy response in breast cancer: systematic review and meta-analysis.

BACKGROUND: A recurrence score based on a 21-gene expression assay predicts the benefit of adjuvant chemotherapy in oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This systematic review aimed to determine whether the 21-gene expression assay performed on core biopsy at diagnosis predicted pathological complete response (pCR) to neoadjuvant chemotherapy. METHODS: The study was performed according to PRISMA guidelines. Relevant databases were searched to identify studies assessing the value of the 21-gene expression assay recurrence score in predicting response to neoadjuvant chemotherapy in patients with breast cancer. The Newcastle-Ottawa Scale was used to assess the quality of the studies. Results are reported as risk ratio (RR) with 95 per cent confidence interval using the Cochrane-Mantel-Haenszel method for meta-analysis. Sensitivity analyses were carried out where appropriate. RESULTS: Seven studies involving 1744 patients reported the correlation between pretreatment recurrence score and pCR. Of these, 777 patients (44.6 per cent) had a high recurrence score and 967 (55.4 per cent) a low-intermediate score. A pCR was achieved in 94 patients (5.4 per cent). The pCR rate was significantly higher in the group with a high recurrence score than in the group with a low-intermediate score (10.9 versus 1.1 per cent; RR 4.47, 95 per cent c.i. 2.76 to 7.21; P < 0.001). A significant risk difference was observed between the two groups (risk difference 0.10, 0.04 to 0.15; P = 0.001). CONCLUSION: A high recurrence score is associated with higher pCR rates and a low-intermediate recurrence score may indicate chemoresistance. Routine assessment of recurrence score by the 21-gene expression assay on core biopsy might be of value when considering neoadjuvant chemotherapy in patients with ER-positive, HER2-negative breast cancer.

Meta-analysis of the impact of progesterone receptor status on oncological outcomes in oestrogen receptor-positive breast cancer.

BACKGROUND: Assessment of the oestrogen receptor (ER) provides important prognostic information in breast cancer. The impact of progesterone receptor (PgR) status is less clear. Standardization of immunohistochemical analysis of these receptors has reduced interstudy heterogeneity. The aim of this meta-analysis was to evaluate the impact of PgR negativity on outcomes in ER-positive (ER+) breast cancer. METHODS: This study was performed according to PRISMA and MOOSE guidelines. PubMed, Embase and the Cochrane Library were searched systematically to identify studies comparing disease-free survival as the primary outcome and overall survival as secondary outcome between PgR-positive (PgR+) and PgR-negative (PgR-) status in ER+ breast cancer. A meta-analysis of time-to-effect measures from included studies was undertaken. RESULTS: Eight studies including 13 667 patients, 11 838 in the ER+PgR+ group and 1829 in the ER+PgR- group, met the inclusion criteria. Treatment characteristics did not differ significantly between the two groups. Patients in the ER+PgR- group had a higher risk of disease recurrence than those who had ER+PgR+ disease (hazard ratio (HR) 1·57, 95 per cent c.i. 1·38 to 1·79; P < 0·001). This hazard was increased in patients with human epidermal growth factor receptor 2-negative tumours (HR 1·62, 1·37 to 1·93; P < 0·001). A similar result was observed for overall survival (HR 1·69, 1·33 to 2·14; P < 0·001). CONCLUSION: PgR negativity is associated with significant reductions in disease-free and overall survival in ER+ breast cancer. Treatment and surveillance strategies in these patients should be tailored accordingly.

ANTECEDENTES: La evaluación del receptor de estrógenos (oestrogen receptor, ER) proporciona una importante información pronóstica en el cáncer de mama. El impacto de del estado del receptor de la progesterona (progesterone receptor, PgR) está menos claro. La estandarización del análisis inmunohistoquímico de estos receptores ha reducido la heterogeneidad entre los estudios. El objetivo de este metaanálisis fue evaluar el impacto de la negatividad de PgR (PgR-) en los resultados del cáncer de mama ER positivo (ER+). MÉTODOS: Este estudio se realizó de acuerdo con las directrices PRISMA/MOOSE. Se llevó a cabo una búsqueda sistemática en MEDLINE, PubMed y biblioteca Cochrane para identificar estudios que comparasen la supervivencia libre de enfermedad (disease free survival, DFS) como resultado primario y la supervivencia global (overall survival, OS) como resultado secundario entre los estados PgR+ y PgR- en el cáncer de mama ER+. Se realizó un metaanálisis de los estudios incluidos de las medidas de tiempo hasta el efecto. RESULTADOS: Ocho estudios que incluían 13.533 pacientes, 11.724 en el grupo ER+PgR+ y 1.809 en el grupo ER+PgR- cumplieron con los criterios de inclusión. Las características del tratamiento no diferían significativamente entre los dos grupos. Los pacientes en el grupo ER+PgR- presentaron un riesgo más elevado de recidiva de la enfermedad que aquellas que tenían enfermedad ER+PgR+ (DFS, cociente de riesgos instantáneos, hazard ratio, HR 1,57; i.c. del 95% 1,38-1,79; P < 0,001). Este riesgo se incrementó en pacientes que eran HER2 negativo (DFS HR 1,62; i.c. del 95% 1,37-1,93; P < 0,001). Un resultado similar se observó para la OS (HR 1,69; i.c. del 95% 1,33-2,14, P < 0,001). CONCLUSIÓN: La negatividad de PgR se asocia con disminuciones significativas de DFS y OS en el cáncer de mama ER+. En estas pacientes, las estrategias de tratamiento y seguimiento en deberán adecuarse a cada caso particular.

Systematic review and meta-analysis comparing primary resection and anastomosis versus Hartmann's procedure for the management of acute perforated diverticulitis with generalised peritonitis.

BACKGROUND: Surgical strategies for acute perforated diverticulitis with generalised peritonitis remain controversial. This study aimed to meta-analyse trials comparing primary resection and anastomosis (PRA) to Hartmann's procedure (HP) for Hinchey III/IV diverticulitis. METHODS: A systematic literature search was conducted to identify observational studies and randomised control trials (RCTs) of patients with Hinchey III/IV diverticulitis undergoing sigmoidectomy that compared PRA to HP. The methodological quality of the included studies was assessed systematically (Newcastle-Ottawa, Jadad and Cochrane risk of bias scores) and a meta-analysis was performed. RESULTS: After removal of duplicates, 12 studies including 4 RCTs were identified. The analysis included 918 patients, of whom 367 (39.98%) underwent PRA. Both the initial stoma rate (risk ratio [RR] persistent stoma 0.43, 95% confidence interval [CI] 0.26, 0.71, p = 0.001; I2 = 99%, p < 0.0001) and the rate of permanent stoma after combining the first (emergency surgery) and second (stoma reversal) procedures were lower in the PRA group. There was no difference in in 30-day mortality; however, PRA resulted in a reduction in overall mortality as well as major complications after the initial operation (RR 0.67, 95% CI 0.46, 0.97, p = 0.03; I2 = 22%, p = 0.26), stoma reversal (RR 0.48, 95% CI 0.26, 0.92, p = 0.03; I2 = 0%, p = 0.58) and when combining both procedures (RR 0.67, 95% CI 0.51, 0.88, p = 0.005; I2 = 0%, heterogeneity p = 0.58). A subgroup analysis of stoma reversal rates using data from only RCTs were consistent (RR permanent stoma, 0.33, 95% CI 0.13, 0.85, p = 0.02; I2 = 77%, p = 0.004) with the findings of the overall analysis. CONCLUSIONS: This meta-analysis demonstrates that PRA used in the management of haemodynamically stable patients with Hinchey grade III/IV diverticulitis leads to a lower overall persistent stoma rate, with reduced morbidity compared with the traditional management.

Merkel Cell Carcinoma: A Case Series

Introduction Merkel cell carcinoma (MCC) is a rare cutaneous tumour that is clinically aggressive with a high local, regional, and distant metastatic potential. Cases Three male patients presented to University Hospital Limerick (UHL) in 2015 with cutaneous lesions of the thorax, buttock and forearm. Once MCC was confirmed, management included surgical wide local excision (WLE) with regional lymph node dissection followed by adjuvant radiotherapy. One patient is in remission. The second has residual locoregional lymph node disease and is undergoing annual CT surveillance. The third had distant metastatic disease and is deceased from an unrelated condition. Discussion This case series highlights the presentation and management of MCC. We also discus relevant guidelines. The management of MCC is complex and there is a need to establish local or national databases to identify and monitor patients with MCC.

C-reactive protein as a predictor of anastomotic leak in the first week after anterior resection for rectal cancer.

AIM: Anastomotic leak (AL) after anterior resection results in increased morbidity, mortality and local recurrence. The aim of this study was to assess the ability of C-reactive protein (CRP) to predict AL in the first week after anterior resection for rectal cancer. METHOD: A retrospective review of a prospectively maintained database that included all patients undergoing anterior resection between January 2008 and December 2013 was performed. The ability of CRP to predict AL was assessed using area under the receiver-operating characteristics (AUC) curves. The severity of AL was defined using the International Study Group of Rectal Cancer (ISREC) grading system. RESULTS: Two-hundred and eleven patients were included in the study. Statistically significant differences in mean CRP values were found between those with and without an AL on postoperative days 5, 6 and 7. A CRP value of 132 mg/l on postoperative day 5 had an AUC of 0.75, corresponding to a sensitivity of 70%, a specificity of 76.6%, a positive predictive value of 16.3% and a negative predictive value of 97.5%. Multivariable analysis found that a CRP of > 132 mg/l on postoperative day 5 was the only statistically significant patient factor that was linked to an increased risk of AL (HR = 8.023, 95% CI: 1.936-33.238, P = 0.004). CONCLUSION: Early detection of AL may minimize postoperative complications. CRP is a useful negative predictive test for the development of AL following anterior resection.

The impact of the Biomolecular Era on breast cancer surgery.

Surgery has always played a central role in the management of breast cancer, with local control via complete tumour resection long established as the cornerstone of effective breast cancer therapy. While extensive surgical resection in the form of the Halstead radical mastectomy dominated treatment up until at least the 1970s, the advent of adjuvant loco-regional and systemic therapies has resulted in a decrease in the magnitude of surgical intervention in recent decades. The Biomolecular or "-omics" era initiated with the discovery of the DNA double helix in 1953 and intensified by the completion of the human genome project in 2003 has seen an unprecedented expansion in our understanding of the molecular and genetic heterogeneity of cancer. This review will discuss how the clinical application of this knowledge in the direction of personalised risk assessment and breast cancer treatment has significant implications for modern surgical practice.

Investigation of 7-dehydrocholesterol reductase pathway to elucidate off-target prenatal effects of pharmaceuticals: a systematic review.

Mendelian diseases contain important biological information regarding developmental effects of gene mutations that can guide drug discovery and toxicity efforts. In this review, we focus on Smith-Lemli-Opitz syndrome (SLOS), a rare Mendelian disease characterized by compound heterozygous mutations in 7-dehydrocholesterol reductase (DHCR7) resulting in severe fetal deformities. We present a compilation of SLOS-inducing DHCR7 mutations and the geographic distribution of those mutations in healthy and diseased populations. We observed that several mutations thought to be disease causing occur in healthy populations, indicating an incomplete understanding of the condition and highlighting new research opportunities. We describe the functional environment around DHCR7, including pharmacological DHCR7 inhibitors and cholesterol and vitamin D synthesis. Using PubMed, we investigated the fetal outcomes following prenatal exposure to DHCR7 modulators. First-trimester exposure to DHCR7 inhibitors resulted in outcomes similar to those of known teratogens (50 vs 48% born-healthy). DHCR7 activity should be considered during drug development and prenatal toxicity assessment.

A Positive Node on Ultrasound-Guided Fine Needle Aspiration Predicts Higher Nodal Burden Than a Positive Sentinel Lymph Node Biopsy in Breast Carcinoma.

INTRODUCTION: Axillary status remains an important prognostic indicator in breast cancer. Certain patients with a positive sentinel node (SLNB) may not benefit from axillary clearance (AC). Uncertainty remains if this approach could be applied to patients diagnosed with axillary metastases on ultrasound-guided fine needle aspiration cytology (USFNAC). The aim of this study was to compare nodal burden in patients with positive USFNAC and a positive SLNB. METHODS: A retrospective study was performed involving all BC patients between 2007 and 2014 who had either pre-operative USFNAC or a SLNB. Patient/tumour characteristics and nodal burden were examined in all patients proceeding to AC. RESULTS: 974 patients were eligible for analysis. 439 patients (45 %) had positive USFNAC and 535 (55 %) had a positive SLNB. USFNAC-positive patients were more likely to undergo mastectomy (Chi-square test; p < 0.001), have extra-nodal extension (p < 0.001), be oestrogen receptor negative (p < 0.001) and be HER2 positive (p < 0.001). The median total number of lymph nodes (LNs) excised during AC was higher in the USFNAC group (Mann-Whitney test; 23 vs. 21; p < 0.001). The median total number of involved LNs was 3 (range 1-47) in FNAC-positive patients versus 1 (range 1-37) in SLNB-positive patients (p < 0.001). The median number of involved LNs in level 1 was 3 in FNAC-positive patients versus 1 in SLNB-positive patients (p < 0.001). Within the SLN-positive group, 49 % of the patients had only one involved LN, 28 % had two nodes involved and 23 % had ≥3. In comparison, within the FNAC-positive group only 13 % of the patients had one involved LN, 12 % had two nodes involved and 74 % had ≥3. CONCLUSION: Patients with positive USFNAC have more aggressive clinico-pathological characteristics and higher nodal burden compared to SLNB-positive patients. Currently, the authors advocate that patients not receiving neoadjuvant chemotherapy, with a positive USFNAC, should proceed directly to an axillary ALND.

Ebola, Zika and the International Health Regulations - implications for Port Health Preparedness.

BACKGROUND: The outbreak of Ebola Virus Disease in West Africa in 2014-2015 was unprecedented in terms of its scale and consequence.  This, together with the emergence of Zika virus as a Public Health Emergency of International Concern in 2016, has again highlighted the potential for disease to spread across international borders and provided an impetus for countries to review their Port Health preparedness. This report reviews the legislative framework and actions taken under this framework in advancing and improving Port Health preparedness in Ireland, in response to the declaration of the Public Health Emergency of International Concern for Ebola Virus Disease in August 2014. FINDINGS: Infectious disease Shipping and Aircraft Regulations were brought into force in Ireland in 2008 and 2009, respectively. Preparatory actions taken under these and the International Health Regulations necessitated significant levels of cross disciplinary working with other organisations, both within and beyond traditional healthcare settings. Information packs on Ebola Virus Disease were prepared and distributed to airports, airlines, port authorities and shipping agents, and practical exercises were held at relevant sites. Agreements were put in place for contact tracing of passenger and crew on affected conveyances and protocols were established for the management of Medical Declarations of Health from ships coming from West Africa. CONCLUSIONS: The outbreak of Ebola Virus Disease in West Africa resulted in significant strengthening of Ireland's Port Health preparedness, while also highlighting the extent to which preparedness requires ongoing and sustained commitment from all stakeholders, both nationally and internationally, in ensuring that countries are ready when the next threat presents at their borders.

Preparedness of elderly long-term care facilities in HSE East for influenza outbreaks.

Abstract We assessed preparedness of HSE East elderly long-term care facilities for an influenza outbreak, and identified Public Health Department support needs. We surveyed 166 facilities based on the HSE checklist document for influenza outbreaks, with 58% response rate. Client flu vaccination rates were > 75%; leading barriers were client anxiety and consent issues. Target flu vaccine uptake of 40% in staff occurred in 43% of facilities and was associated with staff vaccine administration by afacility-attached GP (p = 0.035), having a facility outbreak plan (p = 0.013) and being anon-HSE run facility (p = 0.013). Leading barriers were staff personal anxiety (94%) and lack of awareness of the protective effect on clients (21%). Eighty-nine percent found Public Health helpful, and requested further educational support and advocacy. Staff vaccine uptake focus, organisational leadership, optimal vaccine provision models, outbreak plans and Public Health support are central to the influenza campaign in elderly long-term care facilities.

Influenza in hospitalized children in Ireland in the pandemic period and the 2010/2011 season: risk factors for paediatric intensive-care-unit admission.

Influenza causes significant morbidity and mortality in children. This study's objectives were to describe influenza A(H1N1)pdm09 during the pandemic, to compare it with circulating influenza in 2010/2011, and to identify risk factors for severe influenza defined as requiring admission to a paediatric intensive care unit (PICU). Children hospitalized with influenza during the pandemic were older, and more likely to have received antiviral therapy than children hospitalized during the 2010/2011 season. In 2010/2011, only one child admitted to a PICU with underlying medical conditions had been vaccinated. The risk of severe illness in the pandemic was higher in females and those with underlying conditions. In 2010/2011, infection with influenza A(H1N1)pdm09 compared to other influenza viruses was a significant risk factor for severe disease. An incremental relationship was found between the number of underlying conditions and PICU admission. These findings highlight the importance of improving low vaccination uptake and increasing the use of antivirals in vulnerable children.

Outbreak of hepatitis A infection associated with the consumption of frozen berries, Ireland, 2013--linked to an international outbreak.

In May 2013, a European alert was issued regarding a hepatitis A virus (HAV) outbreak in Italy. In June 2013, HAV subgenotype IA with an identical sequence was identified in Ireland in three cases who had not travelled to Italy. The investigation consisted of descriptive epidemiology, a case-control study, microbiological testing of human and food specimens, molecular typing of positive specimens and food traceback. We identified 21 outbreak cases (14 confirmed primary cases) with symptom onset between 31 January and 11 October 2013. For the case-control study, we recruited 11 confirmed primary cases and 42 matched controls. Cases were more likely than controls to have eaten berry cheesecake (matched odds ratio (mOR): 12; 95% confidence interval (CI): 1.3-114), whole frozen berries (mOR: 9.5; 95% CI: 1.0-89), yoghurt containing frozen berries (mOR: 6.6, 95% CI: 1.2-37) or raw celery (mOR: 4; 95% CI: 1.2-16). Among cases, 91% had consumed at least one of four products containing frozen berries (mOR: 12; 95% CI: 1.5-94). Sixteen food samples tested were all negative for HAV. As products containing frozen berries were implicated in the outbreak, the public were advised to heat-treat frozen berries before consumption.

Staff support for the Health Service Executive (HSE) global health programme.

The Global Health programme (GHP) within the Health Service Executive (HSE) aims to improve health in developing countries by creating partnerships between Irish and developing world healthcare institutions. To ascertain the level of interest among HSE staff for the GHP a web-based survey was conducted. 1,028 responses were received. Medical professionals, 202 (27.7%) composed the largest category of respondents. The majority, 503 (69.3%) of respondents wished to actively participate in the GHP. 237 (23.1%) staff had previous experience of working in the developing world. This survey highlighted a number of themes respondents considered important for successful partnerships including: reciprocal staff exchange, joint scientific research, the avoidance of "brain drain" and utilising the Internet to link institutions. Less than 1% (2/203) of comments expressed a negative view of the GHP.

Success and failure of dead-time models as applied to hybrid pixel detectors in high-flux applications.

The performance of a single-photon-counting hybrid pixel detector has been investigated at the Australian Synchrotron. Results are compared with the body of accepted analytical models previously validated with other detectors. Detector functionals are valuable for empirical calibration. It is shown that the matching of the detector dead-time with the temporal synchrotron source structure leads to substantial improvements in count rate and linearity of response. Standard implementations are linear up to ∼0.36 MHz pixel(-1); the optimized linearity in this configuration has an extended range up to ∼0.71 MHz pixel(-1); these are further correctable with a transfer function to ∼1.77 MHz pixel(-1). This new approach has wide application both in high-accuracy fundamental experiments and in standard crystallographic X-ray fluorescence and other X-ray measurements. The explicit use of data variance (rather than N(1/2) noise) and direct measures of goodness-of-fit (χ(r)(2)) are introduced, raising issues not encountered in previous literature for any detector, and suggesting that these inadequacies of models may apply to most detector types. Specifically, parametrization of models with non-physical values can lead to remarkable agreement for a range of count-rate, pulse-frequency and temporal structure. However, especially when the dead-time is near resonant with the temporal structure, limitations of these classical models become apparent. Further, a lack of agreement at extreme count rates was evident.

The corona pandemic and participatory governance: Responding to the vulnerabilities of secondary school students in Europe.

Adolescents in secondary schools have limited susceptibility to the SARS-COV-2 virus, but paradoxically are considered to be carrying the highest psychosocial burden during this pandemic. The aim of our European multi-country qualitative research was to investigate the COVID-19 crisis response in secondary schools and the role of national, regional, and local stakeholders in contributing to a participatory governance approach. We carried out 11 months of qualitative fieldwork, which included 90 respondents from the Netherlands, Ireland, and Finland for in-depth interviews and/or group discussions. Participant observation was conducted in four secondary schools to explore the interplay of day-to-day formal and informal practices of crisis governance. Our findings contribute to a better understanding of what efforts were made to facilitate participatory governance and where a bottom-up approach would have served useful in successfully implementing the COVID-19 mitigation strategies. Moreover, we show how these mitigation strategies have led to unintended consequences, such as students' difficulties with isolation and associated mental health problems, and the struggles of socialization when returning to a physical school environment. Our findings highlight the importance of the school environment in the socio-emotional developments of adolescents. We introduce the TAPIC-R model to analyze good governance, advancing the existing TAPIC model with an emphasis on the role of resilience in shaping participatory governance. We argue this is urgently needed during crises to strengthen engagement of the community, including vulnerable groups and achieve positive outcomes within and across policy structures and action domains.

Observation of picometer vertical emittance with a vertical undulator.

Using a vertical undulator, picometer vertical electron beam emittances have been observed at the Australian Synchrotron storage ring. An APPLE-II type undulator was phased to produce a horizontal magnetic field, which creates a synchrotron radiation field that is very sensitive to the vertical electron beam emittance. The measured ratios of undulator spectral peak heights are evaluated by fitting to simulations of the apparatus. With this apparatus immediately available at most existing electron and positron storage rings, we find this to be an appropriate and novel vertical emittance diagnostic.