Breast-Conserving Surgery with or without Irradiation in Early Breast Cancer.

BACKGROUND: Limited level 1 evidence is available on the omission of radiotherapy after breast-conserving surgery in older women with hormone receptor-positive early breast cancer receiving adjuvant endocrine therapy. METHODS: We performed a phase 3 randomized trial of the omission of irradiation; the trial population included women 65 years of age or older who had hormone receptor-positive, node-negative, T1 or T2 primary breast cancer (with tumors ≤3 cm in the largest dimension) treated with breast-conserving surgery with clear excision margins and adjuvant endocrine therapy. Patients were randomly assigned to receive whole-breast irradiation (40 to 50 Gy) or no irradiation. The primary end point was local breast cancer recurrence. Regional recurrence, breast cancer-specific survival, distant recurrence as the first event, and overall survival were also assessed. RESULTS: A total of 1326 women were enrolled; 658 were randomly assigned to receive whole-breast irradiation and 668 to receive no irradiation. The median follow-up was 9.1 years. The cumulative incidence of local breast cancer recurrence within 10 years was 9.5% (95% confidence interval [CI], 6.8 to 12.3) in the no-radiotherapy group and 0.9% (95% CI, 0.1 to 1.7) in the radiotherapy group (hazard ratio, 10.4; 95% CI, 4.1 to 26.1; P<0.001). Although local recurrence was more common in the group that did not receive radiotherapy, the 10-year incidence of distant recurrence as the first event was not higher in the no-radiotherapy group than in the radiotherapy group, at 1.6% (95% CI, 0.4 to 2.8) and 3.0% (95% CI, 1.4 to 4.5), respectively. Overall survival at 10 years was almost identical in the two groups, at 80.8% (95% CI, 77.2 to 84.3) with no radiotherapy and 80.7% (95% CI, 76.9 to 84.3) with radiotherapy. The incidence of regional recurrence and breast cancer-specific survival also did not differ substantially between the two groups. CONCLUSIONS: Omission of radiotherapy was associated with an increased incidence of local recurrence but had no detrimental effect on distant recurrence as the first event or overall survival among women 65 years of age or older with low-risk, hormone receptor-positive early breast cancer. (Funded by the Chief Scientist Office of the Scottish Government and the Breast Cancer Institute, Western General Hospital, Edinburgh; ISRCTN number, ISRCTN95889329.).

Increasing incidence of endometrial cancer in Aotearoa New Zealand: Health professionals' perspective.

BACKGROUND: The incidence of endometrial cancer is globally increasing. Aotearoa New Zealand is no exception with a 59% increase in cases over that last ten years. AIMS: We report a sub-set of themes which pertain to provider reflections of rising endometrioid-type endometrial cancer incidence in individuals with high weight. MATERIALS AND METHODS: Fifteen semi-structured interviews with healthcare professionals experienced in providing care to women with endometrial cancer were audio-recorded and transcribed. Interviews were analysed using reflexive thematic analysis. RESULTS: Two main themes emerged: (1) concerns for the future; and (2) impact on fertility and treatment options. Healthcare professionals discussed rising incidence in younger people and a need for increased awareness about the association of excess weight as a risk factor for developing the disease. The concern extended to workforce and equipment shortfalls of meeting the needs of individuals with higher weight, which subsequently influenced treatment options, health outcomes and survivorship. CONCLUSIONS: Rising incidence of endometrial cancer in individuals with high weight presents multiple chances for inequitable access and health outcomes over the care continuum for endometrial cancer. Action is required to address incidence, awareness, access to equitable and inclusive treatment, and survivorship.

Environmental impact of a blood test reduction intervention in adult intensive care units: A before and after quality improvement project.

BACKGROUND: Pathology testing is a very common investigation in the intensive care unit (ICU). Many tests are ordered on a routine basis rather than for a specific clinical indication, resulting in potential patient harm and unnecessary financial and environmental costs. OBJECTIVE: The objective of this study was to determine whether a multifaceted intervention based on the principles of education, audit, and feedback can result in a decrease in unnecessary pathology tests without a commensurate increase in adverse patient outcomes and to measure this decrease in terms of the associated reduction in environmental and financial costs. METHODS: A before and after quality improvement project was conducted between 2017 and 2019 across four ICUs in three 12-month phases, divided according to baseline, intervention implementation, and follow-up. Local clinician champions from each site partnered with the project coordinating centre to develop and implement a range of interventions based on the principles of education, audit, and feedback. Data were collected for the number of pathology tests performed and the clinical characteristics of patients admitted to a participating ICU across the three phases. RESULTS: A total of 196 323 arterial blood gases and 460 258 other tests across eight categories were performed on the 22 210 patients admitted to participating ICUs during the project. A decrease in testing was observed across all but one category, with the greatest reduction seen in arterial blood gases (31.2% reduction in tests per bed-day). Across all categories, this equated to a mean reduction of 1.8 tCO2e (tonnes of carbon dioxide equivalent), a potential estimated total saving of Australian dollar $918 497.50. No increase in adverse clinical outcomes was observed. CONCLUSION: A multifaceted intervention based on the principles of education, audit, and feedback can produce a significant decrease in the number of unnecessary pathology tests performed. This reduction translates to substantial environmental and financial savings without any associated increase in adverse patient outcomes.

Evaluation of the association of area-level socioeconomic deprivation and breast cancer recurrence by oestrogen receptor subtypes in Scotland.

BACKGROUND: Women from socioeconomically deprived areas have lower breast cancer (BC) incidence rates for screen-detected oestrogen receptor (ER) + tumours and higher mortality for select tumour subtypes. We aimed to determine if ipsilateral breast cancer recurrence (IBR) differs by Scottish Index of Multiple Deprivation (SIMD) quintile and tumour subtype in Scotland. METHODS: Patient data for primary invasive BC diagnosed in 2007-2008 in Scotland was analysed. Manual case-note review for 3495 patients from 10 years post-diagnosis was used. To determine the probability of IBR while accounting for the competing risk of death from any cause, cumulative incidence functions stratified by ER subtype and surgery were plotted. Multivariable Cox Proportional Hazards models were used to estimate the association of SIMD accounting for other predictors of IBR. RESULTS: Among 2819 ER + tumours, 423 patients had a recurrence and 438 died. SIMD was related to death (p = 0.018) with the most deprived more likely to have died in the 10-year period (17.7% vs. 12.9%). We found no significant differences by SIMD in prognostic tumour characteristics (grade, TNM stage, treatment, screen-detection) or risk of IBR. Among 676 patients diagnosed with ER- tumours, 105 died and 185 had a recurrence. We found no significant differences in prognostic tumour characteristics by SIMD except screen detection with the most deprived more likely than the least to have their tumours detected from screening (46.9% vs. 28%, p = 0.03). Among patients with ER- tumours, 50% had mastectomy and the most deprived had increased 5-year IBR risk compared to the least deprived (HR 3.03 [1.41-6.53]). CONCLUSIONS: IBR is not a major contributor to mortality differences by SIMD for the majority of BC patients in our study. The lack of inequities in IBR are likely due to standardised treatment protocols and access to healthcare. The association with socioeconomic deprivation and recurrence for ER- tumours requires further study.

The VA National Teleneurology Program (NTNP): Implementing Teleneurology to Improve Equitable Access to Outpatient Neurology Care.

BACKGROUND: Telehealth is increasingly utilized in many healthcare systems to improve access to specialty care and better allocate limited resources, especially for rurally residing persons who face unique barriers to care. OBJECTIVES: The VHA sought to address critical gaps in access to neurology care by developing and implementing the first outpatient National Teleneurology Program (NTNP). DESIGN: Pre-post evaluation of intervention and control sites. PARTICIPANTS: NTNP sites and VA control sites; Veterans completing an NTNP consult and their referring providers. INTERVENTION: Implementation of the NTNP at participating sites. MAIN MEASURES: NTNP and community care neurology (CCN) volume of consults before and after implementation; time to schedule and complete consults; Veteran satisfaction. KEY RESULTS: In FY2021, the NTNP was implemented at 12 VA sites; 1521 consults were placed and 1084 (71.3%) were completed. NTNP consults were scheduled (10.1 vs 29.0 days, p < 0.001) and completed (44.0 vs 96.9 days, p < 0.001) significantly faster than CCN consults. Post-implementation, monthly CCN consult volume was unchanged at NTNP sites compared to pre-implementation (mean change of 4.6 consults per month, [95% CI - 4.3, 13.6]), but control sites had a significant increase (mean change of 24.4 [5.2, 43.7]). The estimated difference in mean change in CCN consults between NTNP and control sites persisted after adjusting for local neurology availability (p < 0.001). Veterans (N = 259) were highly satisfied with NTNP care (mean (SD) overall satisfaction score 6.3 (1.2) on a 7-point Likert scale). CONCLUSIONS: Implementation of NTNP resulted in more timely neurologic care than care in the community. The observed significant increase in monthly CCN consults at non-participating sites during the post-implementation period was not seen at NTNP sites. Veterans were highly satisfied with Teleneurology care.

Making Sense of Late Tissue Nodules Associated With Hyaluronic Acid Injections.

BACKGROUND: The pathogenesis of delayed-onset tissue nodules (DTNs) due to hyaluronic acid (HA) injections is uncertain. OBJECTIVES: To formulate a rational theory for DTN development and their avoidance and treatment. METHODS: A multidisciplinary and multicountry DTN consensus panel was established, with 20 questions posed and consensus sought. Consensus was set at 75% agreement. RESULTS: Consensus was reached in 16 of 20 questions regarding the pathogenesis of DTNs, forming the basis for a classification and treatment guide. CONCLUSIONS: The group believes that filler, pathogens, and inflammation are all involved in DTNs and that DTNs most likely are infection initiated with a variable immune response. Injected filler may incorporate surface bacteria, either a commensal or a true pathogen, if the skin barrier is altered. The initially high molecular weight HA filler is degraded to low molecular weight HA (LMWHA) at the edge of the filler. Commensals positioned within the filler bolus may be well tolerated until the filler is degraded and the commensal becomes visible to the immune system. LMWHA is particularly inflammatory in the presence of any local bacteria. Commensals may still be tolerated unless the immune system is generally heightened by viremia or vaccination. Systemic pathogenic bacteremia may also interact with the filler peripheral LMWHA, activating Toll-like receptors that induce DTN formation. Given this scenario, attention to practitioner and patient hygiene and early systemic infection treatment deserve attention. Classification and treatment systems were devised by considering each of the 3 factors-filler, inflammation, and infection-separately.

The Value of In Vivo Reflectance Confocal Microscopy as an Assessment Tool in Chemotherapy-Induced Peripheral Neuropathy: A Pilot Study.

BACKGROUND: There is a lack of standardized objective and reliable assessment tools for chemotherapy-induced peripheral neuropathy (CIPN). In vivo reflectance confocal microscopy (RCM) imaging offers a non-invasive method to identify peripheral neuropathy markers, namely Meissner's corpuscles (MC). This study investigated the feasibility and value of RCM in CIPN. PATIENTS AND METHODS: Reflectance confocal microscopy was performed on the fingertip to evaluate MC density in 45 healthy controls and 9 patients with cancer (prior, during, and post-chemotherapy). Quantification was completed by 2 reviewers (one blinded), with maximum MC count/3 × 3 mm image reported. Quantitative Sensory Testing (QST; thermal and mechanical detection thresholds), Grooved pegboard test, and patient-reported outcomes measures (PROMS) were conducted for comparison. RESULTS: In controls (25 females, 20 males; 24-81 years), females exhibited greater mean MC density compared with males (49.9 ± 7.1 vs 30.9 ± 4.2 MC/3 × 3 mm; P = .03). Differences existed across age by decade (P < .0001). Meissner's corpuscle density was correlated with mechanical detection (ρ = -0.51), warm detection (ρ = -0.47), cold pain (ρ = 0.49) thresholds (P < .01); and completion time on the Grooved pegboard test in both hands (P ≤ .02). At baseline, patients had reduced MC density vs age and gender-matched controls (P = .03). Longitudinal assessment of MC density revealed significant relationships with QST and PROMS. Inter-rater reliability of MC count showed an intraclass correlation of 0.96 (P < .0001). CONCLUSIONS: The findings support the clinical utility of RCM in CIPN as it provides meaningful markers of sensory nerve dysfunction. Novel, prospective assessment demonstrated the ability to detect subclinical deficits in patients at risk of CIPN and potential to monitor neuropathy progression.

Breast cancer incidence and survival in Scotland by socio-economic deprivation and tumour subtype.

BACKGROUND: Women from socio-economically deprived areas are less likely to develop and then to survive breast cancer (BC). Whether associations between deprivation and BC incidence and survival differ by tumour molecular subtypes and mode of detection in Scotland are unknown. METHODS: Data consisted of 62,378 women diagnosed with invasive BC between 2000 and 2016 in Scotland. Incidence rates and time trends were calculated for oestrogen receptor positive (ER+) and negative (ER-) tumours and stratified by the Scottish Index of Multiple Deprivation (SIMD) quintiles and screening status. SIMD is an area-based measure derived across seven domains: income, employment, education, health, access to services, crime and housing. We calculated adjusted hazard ratios (aHR [95% confidence intervals]) for BC death by immunohistochemical surrogates of molecular subtypes for the most versus the least deprived quintile. We adjusted for mode of detection and other confounders. RESULTS: In Scotland, screen-detected ER+tumour incidence increased over time, particularly in the least deprived quintile [Average Annual Percentage Change (AAPC) = 2.9% with 95% CI from 1.2 to 4.7]. No marked differences were observed for non-screen-detected ER+tumours or ER- tumours by deprivation. BC mortality was higher in the most compared to the least deprived quintile irrespective of ER status (aHR = 1.29 [1.18, 1.41] for ER+ and 1.27 [1.09, 1.47] for ER- tumours). However, deprivation was associated with significantly higher mortality for luminal A and HER2-enriched tumours (aHR = 1.46 [1.13, 1.88] and 2.10 [1.23, 3.59] respectively) but weaker associations for luminal B and TNBC tumours that were not statistically significant. CONCLUSIONS: Deprivation is associated with differential BC incidence trends for screen-detected ER+tumours and with higher mortality for select tumour subtypes. Future efforts should evaluate factors that might be associated with reduced survival in deprived populations and monitor progress stratified by tumour subtypes and mode of detection.

One-Year Costs Associated With the Veterans Affairs National TeleStroke Program.

OBJECTIVES: Access to timely care is important for patients with stroke, where rapid diagnosis and treatment affect functional status, disability, and mortality. Telestroke programs connect stroke specialists with emergency department staff at facilities without on-site stroke expertise. The objective of this study was to examine healthcare costs for patients with stroke who sought care before and after implementation of the US Department of Veterans Affairs National TeleStroke Program (NTSP). METHODS: We identified 471 patients who had a stroke and sought care at a telestroke site and compared them to 529 patients with stroke who received stroke care at the same sites before telestroke implementation. We examined patient costs for 12 months before and after stroke, using a linear model with a patient-level fixed effect. RESULTS: NTSP was associated with significantly higher rates of patients receiving guideline concordant care. Compared with control patients, those treated by NTSP were 14.3 percentage points more likely to receive tissue plasminogen activator and 4.3 percentage points more likely to receive a thrombectomy (all P < .0001). NTSP was associated with $4821 increased costs for patients with stroke in the first 30 days after the program (2019 dollars). There were no observed savings over 12 months, and the added costs of care were attributable to higher rates of guideline concordant care. CONCLUSIONS: Telestroke programs are unlikely to yield short-term savings because optimal stroke care is expensive. Healthcare organizations should expect increases in healthcare costs for patients treated for stroke in the first year after implementing a telestroke program.

Interventions for perceptual disorders following stroke.

BACKGROUND: Perception is the ability to understand information from our senses. It allows us to experience and meaningfully interact with our environment. A stroke may impair perception in up to 70% of stroke survivors, leading to distress, increased dependence on others, and poorer quality of life. Interventions to address perceptual disorders may include assessment and screening, rehabilitation, non-invasive brain stimulation, pharmacological and surgical approaches. OBJECTIVES: To assess the effectiveness of interventions aimed at perceptual disorders after stroke compared to no intervention or control (placebo, standard care, attention control), on measures of performance in activities of daily living.  SEARCH METHODS: We searched the trials registers of the Cochrane Stroke Group, CENTRAL, MEDLINE, Embase, and three other databases to August 2021. We also searched trials and research registers, reference lists of studies, handsearched journals, and contacted authors. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of adult stroke survivors with perceptual disorders. We defined perception as the specific mental functions of recognising and interpreting sensory stimuli and included hearing, taste, touch, smell, somatosensation, and vision. Our definition of perception excluded visual field deficits, neglect/inattention, and pain. DATA COLLECTION AND ANALYSIS: One review author assessed titles, with two review authors independently screening abstracts and full-text articles for eligibility. One review author extracted, appraised, and entered data, which were checked by a second author. We assessed risk of bias (ROB) using the ROB-1 tool, and quality of evidence using GRADE.  A stakeholder group, comprising stroke survivors, carers, and healthcare professionals, was involved in this review update. MAIN RESULTS: We identified 18 eligible RCTs involving 541 participants. The trials addressed touch (three trials, 70 participants), somatosensory (seven trials, 196 participants) and visual perception disorders (seven trials, 225 participants), with one (50 participants) exploring mixed touch-somatosensory disorders. None addressed stroke-related hearing, taste, or smell perception disorders. All but one examined the effectiveness of rehabilitation interventions; the exception evaluated non-invasive brain stimulation. For our main comparison of active intervention versus no treatment or control, one trial reported our primary outcome of performance in activities of daily living (ADL):  Somatosensory disorders: one trial (24 participants) compared an intervention with a control intervention and reported an ADL measure.  Touch perception disorder: no trials measuring ADL compared an intervention with no treatment or with a control intervention.  Visual perception disorders: no trials measuring ADL compared an intervention with no treatment or control.  In addition, six trials reported ADL outcomes in a comparison of active intervention versus active intervention, relating to somatosensation (three trials), touch (one trial) and vision (two trials).   AUTHORS' CONCLUSIONS: Following a detailed, systematic search, we identified limited RCT evidence of the effectiveness of interventions for perceptual disorders following stroke. There is insufficient evidence to support or refute the suggestion that perceptual interventions are effective. More high-quality trials of interventions for perceptual disorders in stroke are needed. They should recruit sufficient participant numbers, include a 'usual care' comparison, and measure longer-term functional outcomes, at time points beyond the initial intervention period. People with impaired perception following a stroke should continue to receive neurorehabilitation according to clinical guidelines.

Provider Communication and Telepresence Enhance Veteran Satisfaction With Telestroke Consultations.

BACKGROUND AND PURPOSE: Telestroke has been demonstrated to be a cost-effective means to expand access to care and improve outcomes in stroke; however, information on patient perceptions of this system of care delivery are limited. This study seeks to examine patient feedback of a national telestroke system within the Veterans Health Administration. METHODS: Patients who received a telestroke consultation were eligible for a phone interview 2 weeks later, including questions about technology quality, telepresence, and telestroke provider communication. Satisfaction scores ranged from 1 to 7 (higher=more satisfied) and for analyses were dichotomized as 6 to 7 indicating high satisfaction versus <6. Patient variables including stroke severity (measured by the National Institutes of Health Stroke Scale) were obtained from study records. Generalized estimating equation models were used to determine what factors were associated with patient satisfaction. RESULTS: Over 18 months, 186 interviews were completed, and 142 (76%) reported high satisfaction with telestroke. Patients with more severe stroke were less likely to recall the consultation. Factors significantly associated with patient satisfaction were higher ratings of the technology (P<0.0001), telepresence (P<0.0001), provider communication ratings (P<0.0001), and overall Veterans Affairs satisfaction (P=0.02). In the multivariate model, telepresence (odds ratio, 3.10 [95% CI, 1.81-5.31]) and provider ratings (odds ratio, 2.37 [95% CI, 1.20-4.68]) were independently associated with satisfaction. Veterans who were satisfied were more likely to recommend the technology (P<0.0001). CONCLUSIONS: Provider qualities, including telepresence and provider ratings, were associated with overall Veteran satisfaction with the telestroke consultation. Technology quality may be necessary but not sufficient to impact patient experience. Training providers to improve telepresence could improve patient experience with telestroke consultation.

Development and Validation of a 30-Day In-hospital Mortality Model Among Seriously Ill Transferred Patients: a Retrospective Cohort Study.

BACKGROUND: Predicting the risk of in-hospital mortality on admission is challenging but essential for risk stratification of patient outcomes and designing an appropriate plan-of-care, especially among transferred patients. OBJECTIVE: Develop a model that uses administrative and clinical data within 24 h of transfer to predict 30-day in-hospital mortality at an Academic Health Center (AHC). DESIGN: Retrospective cohort study. We used 30 putative variables in a multiple logistic regression model in the full data set (n = 10,389) to identify 20 candidate variables obtained from the electronic medical record (EMR) within 24 h of admission that were associated with 30-day in-hospital mortality (p < 0.05). These 20 variables were tested using multiple logistic regression and area under the curve (AUC)-receiver operating characteristics (ROC) analysis to identify an optimal risk threshold score in a randomly split derivation sample (n = 5194) which was then examined in the validation sample (n = 5195). PARTICIPANTS: Ten thousand three hundred eighty-nine patients greater than 18 years transferred to the Indiana University (IU)-Adult Academic Health Center (AHC) between 1/1/2016 and 12/31/2017. MAIN MEASURES: Sensitivity, specificity, positive predictive value, C-statistic, and risk threshold score of the model. KEY RESULTS: The final model was strongly discriminative (C-statistic = 0.90) and had a good fit (Hosmer-Lemeshow goodness-of-fit test [X2 (8) =6.26, p = 0.62]). The positive predictive value for 30-day in-hospital death was 68%; AUC-ROC was 0.90 (95% confidence interval 0.89-0.92, p < 0.0001). We identified a risk threshold score of -2.19 that had a maximum sensitivity (79.87%) and specificity (85.24%) in the derivation and validation sample (sensitivity: 75.00%, specificity: 85.71%). In the validation sample, 34.40% (354/1029) of the patients above this threshold died compared to only 2.83% (118/4166) deaths below this threshold. CONCLUSION: This model can use EMR and administrative data within 24 h of transfer to predict the risk of 30-day in-hospital mortality with reasonable accuracy among seriously ill transferred patients.

Antiherpetic medication and incident dementia: Observational cohort studies in four countries.

BACKGROUND AND PURPOSE: Several epidemiological studies from Taiwan, all using the same data resource, found significant associations between herpes virus infection, antiherpetic medication, and subsequent dementia. We conducted a multicenter observational cohort study using health registry data from Wales, Germany, Scotland, and Denmark to investigate potential associations between antiherpetic medication and incident dementia, and also to comprehensively investigate such associations broken down according to medication type and dose, type of herpes virus, and dementia subtype. METHODS: A total of 2.5 million individuals aged 65 years or more were followed up using linked electronic health records in four national observational cohort studies. Exposure and outcome were classified using coded data from primary and secondary care. Data were analyzed using survival analysis with time-dependent covariates. RESULTS: Results were heterogeneous, with a tendency toward decreased dementia risk in individuals exposed to antiherpetic medication. Associations were not affected by treatment number, herpes subtype, dementia subtype, or specific medication. In one cohort, individuals diagnosed with herpes but not exposed to antiherpetic medication were at higher dementia risk. CONCLUSIONS: Short-term antiherpetic medication is not markedly associated with incident dementia. Because neither dementia subtype nor herpes subtype modified the association, the small but significant decrease in dementia incidence with antiherpetic administration may reflect confounding and misclassification.

Building cohesion in distributed telemedicine teams: findings from the Department of Veterans Affairs National Telestroke Program.

BACKGROUND: As telemedicine adoption increases, so does the importance of building cohesion among physicians in telemedicine teams. For example, in acute telestroke services, stroke specialists provide rapid remote stroke assessment and treatment to patients at hospitals without stroke specialty care. In the National Telestroke Program (NTSP) of the U.S. Department of Veterans Affairs, a virtual (distributed) hub of stroke specialists throughout the country provides 24/7 consultations nationwide. We examined how these specialists adapted to distributed teamwork, and we identified cohesion-related factors in program development and support. METHODS: We studied the virtual hub of stroke specialists employed by the NTSP. Semi-structured, confidential interviews with stroke specialists in the virtual hub were recorded and transcribed. We explored the extent to which these specialists had developed a sense of shared identity and team cohesion, and we identified factors in this development. Using a qualitative approach with constant comparison methods, two researchers coded each interview transcript independently using a shared codebook. We used matrix displays to identify themes, with special attention to team cohesion, communication, trust, and satisfaction. RESULTS: Of 13 specialists with at least 8 months of NTSP practice, 12 completed interviews; 7 had previously practiced in telestroke programs in other healthcare systems. Interviewees reported high levels of trust and team cohesion, sometimes even more with their virtual colleagues than with co-located colleagues. Factors facilitating perceived team cohesion included a weekly case conference call, a sense of transparency in discussing challenges, engagement in NTSP development tasks, and support from the NTSP leadership. Although lack of in-person contact was associated with lower cohesion, annual in-person NTSP meetings helped mitigate this issue. Despite technical challenges in establishing a new telehealth system within existing national infrastructure, providers reported high levels of satisfaction with the NTSP. CONCLUSION: A virtual telestroke hub can provide a sense of team cohesion among stroke specialists at a level comparable with a standard co-located practice. Engaging in transparent discussion of challenging cases, reviewing new clinical evidence, and contributing to program improvements may promote cohesion in distributed telemedicine teams.

Higher Monocyte Count is Associated with 30-Day Case Fatality in Intracerebral Hemorrhage.

BACKGROUND: Previous studies have suggested that elevated neutrophils, monocytes, and neutrophil-to-lymphocyte ratio (NLR) may be associated with poor outcomes in intracerebral hemorrhage (ICH). We sought to determine whether white blood cell (WBC) types were independently associated with poor outcome in ICH in a large cohort. METHODS: We performed a retrospective study of primary ICH at two academic centers. Cases were identified via ICD-9 code and verified via physician review. We included only those patients with WBC types obtained within 24 h of ICH onset. RESULTS: We identified 593 patients with primary ICH and WBC differentials in the first 24 h. Independent factors (OR, 95% CI) associated with 30-day case fatality were age > 80 (2.4 (1.4, 4.2)), p = 0.0023; NIHSS greater than median (3.9 (2.4, 6.3)), p < 0.0001; ICH volume quartiles (Q1: ref, Q2: 1.5 (0.7, 3.0), Q3: 3.2 (1.6, 6.6), Q4: 11.9 (5.3, 26.4)), p < 0.0001; non-lobar location (3.3 (1.9, 5.9)), p ≤ 0.0001; IVH (2.3 (1.4, 3.6)), p = 0.0005, monocytes greater than median (1.6 (1.0, 2.4)), p = 0.0457, and anticoagulant use (3.2 (1.8, 5.6)), p < 0.0001. Elevated NLR was not associated with higher case fatality. CONCLUSIONS: We found that elevated monocytes were independently associated with 30-day case fatality. Future studies will investigate whether there are subgroups of ICH patients, including those with particular blood or imaging biomarkers, in which WBC types might help predict poor outcome and provide targets for intervention.

A critical care pandemic staffing framework in Australia.

BACKGROUND: Pandemics and the large-scale outbreak of infectious disease can significantly impact morbidity and mortality worldwide. The impact on intensive care resources can be significant and often require modification of service delivery, a key element which includes rapid expansion of the critical care workforce. Pandemics are also unpredictable, which necessitates rapid decision-making and action which, in the lack of experience and guidance, may be extremely challenging. Recognising the potential strain on intensive care units (ICUs), particularly on staffing, a working group was formed for the purpose of developing recommendations to support decision-making during rapid service expansion. METHODS: The Critical Care Pandemic Staffing Working Party (n = 21), representing nursing, allied health, and medical disciplines, has used a modified consensus approach to provide recommendations to inform multidisciplinary workforce capacity expansion planning in critical care. RESULTS: A total of 60 recommendations have been proposed which reflect general recommendations as well as those specific to maintaining the critical care workforce, expanding the critical care workforce, rostering and allocation of the critical care workforce, nurse-specific recommendations for staffing the ICU, education support and training during ICU surge situations, workforce support, models of care, and de-escalation. CONCLUSION: These recommendations are provided with the intent that they be used to guide interdisciplinary decision-making, and we suggest that careful consideration is given to the local context to determine which recommendations are most appropriate to implement and how they are prioritised. Ongoing evaluation of recommendation implementation and impact will be necessary, particularly in rapidly changing clinical contexts.

Evaluation of The Practitioner Online Referral and Treatment Service (PORTS): the first 18 months of a state-wide digital service for adults with anxiety, depression, or substance use problems.

The Practitioner Online Referral and Treatment Service (PORTS) is a new digital mental health service (DMHS) providing assessment, treatment, and consultation across Western Australia, for adults with anxiety, depression, or substance use problems, and experiencing financial hardship or geographical disadvantage. From July 2017 to December 2018, a total of 2,527 individuals were referred to PORTS. Of these, 150 (6%) did not give consent for their results to be analysed. Of the remaining 2,377 patients, 615 (26%) could not be contacted to confirm the referral, 596 (25%) received assessment or information from PORTS, 427 (18%) were referred to another service, and 739 (31%) commenced treatment at PORTS. Almost half (47%) of patients were from areas with significant socio-economic disadvantage. Those referred by another mental health service were more likely to engage in treatment than those referred by a General Practitioner (GP). Overall outcomes were excellent, with large effect sizes (Cohen's d: 1.1-1.4), from assessment to post-treatment and 3-month follow-up, reliable deterioration was low, and GP and patient satisfaction was high. These results indicate that the PORTS DMHS model is a promising method for engaging primary care patients with anxiety and depression, including those experiencing financial and geographical disadvantage.

Five-year oncological outcomes after selective neoadjuvant radiotherapy for resectable rectal cancer.

Introduction: There is considerable variation in selection of patients for and type of neoadjuvant radiotherapy administered in the treatment of resectable rectal cancer. The aim of this study was to report outcomes for patients with resected rectal cancer from a unit with step-wise selection for surgery alone, short course radiotherapy (SCRT) or downstaging long course chemoradiotherapy (LCCRT). Material and methods: Cohort analysis of patients with rectal adenocarcinoma resected with curative intent between 2008 and 2012 at a specialist regional colorectal surgery center. The primary endpoints were local recurrence, metastatic recurrence, disease-free survival and overall survival. Exploratory uni- and multi-variable regression analyses were performed to identify predictive factors. Results: About 240 patients were treated by surgery alone, 90 patients received SCRT and 91 patients received LCCRT. Five-year local recurrence was 10.8% in the surgery alone group, 3.3% with SCRT and 18.7% with LCCRT. Metachronous distant metastasis was highest in the SCRT group (13.8% surgery alone, 25.6% SCRT, 15.4% LCCRT). Uni- and multi-variable regression analysis found that local and distant recurrence was attributable predominantly to adverse tumor biology. Conclusions: Patients selected for SCRT had a lower rate of local recurrence than patients selected for surgery alone, but were more likely to develop distant metastasis. There was no difference in overall survival. With low local recurrence rates, distant metastasis is the predominant risk for patients with resectable rectal cancer.

The Role of Informed Consent for Thrombolysis in Acute Ischemic Stroke.

Although tissue plasminogen activator (tPA) is the only medication approved by the United States Food and Drug Administration (FDA) for acute ischemic stroke, there is no consensus about the need for informed consent for its use. As a result, hospitals throughout the U.S. have varying requirements regarding obtaining informed consent from patients for the use of tPA, ranging from no requirement for informed consent to a requirement for verbal or written informed consent. We conducted a study to (1) determine current beliefs about obtaining patients' informed consent for tPA among a large group of stroke clinicians and (2) identify the ethical, clinical, and organizational factors that influence tPA consent practices. Semi-structured interviews were conducted by trained and experienced investigators and research staff to identify key barriers to implementing acute stroke services. Part of the interview explored current beliefs and practices around informed consent for tPA. This was a multicenter study that included 38 Veterans Health Administration (VHA) hospital locations. Participants were 68 stroke team clinicians, serving primarily on the neurology (35 percent) or emergency medicine (41 percent) service. We conducted thematic analysis based on principles of grounded theory to identify codes about consent for tPA. We used interpretive convergence to ensure consistency among the individual investigators' codes and to ensure that all of the investigators agreed on coding and themes. We found that 38 percent of the stroke clinicians did not believe any form of consent was necessary for tPA, 47 percent thought that some form of consent was necessary, and 15 percent were unsure. Clinicians who believed tPA required informed consent were divided on whether consent should be written (40 percent) or verbal (60 percent). We identified three factors describing clinicians' attitudes about consent: (1) legal and policy factors, (2) ethical factors, and (3) medical factors. The lack of consensus regarding consent for tPA creates the potential for delays in treatment, uneasiness among clinicians, and legal liability. The identified factors provide a potential framework to guide discussions about developing a standard of care for acquiring the informed consent of patients for the administration of tPA.

Quality of life after postmastectomy radiotherapy in patients with intermediate-risk breast cancer (SUPREMO): 2-year follow-up results of a randomised controlled trial.

BACKGROUND: Postmastectomy radiotherapy in patients with four or more positive axillary nodes reduces breast cancer mortality, but its role in patients with one to three involved nodes is controversial. We assessed the effects of postmastectomy radiotherapy on quality of life (QOL) in women with intermediate-risk breast cancer. METHODS: SUPREMO is an open-label, international, parallel-group, randomised, controlled trial. Women aged 18 years or older with intermediate-risk breast cancer (defined as pT1-2N1; pT3N0; or pT2N0 if also grade III or with lymphovascular invasion) who had undergone mastectomy and, if node positive, axillary surgery, were randomly assigned (1:1) to receive chest wall radiotherapy (50 Gy in 25 fractions or a radiobiologically equivalent dose of 45 Gy in 20 fractions or 40 Gy in 15 fractions) or no radiotherapy. Randomisation was done with permuted blocks of varying block length, and stratified by centre, without masking of patients or investigators. The primary endpoint is 10-year overall survival. Here, we present 2-year results of QOL (a prespecified secondary endpoint). The QOL substudy, open to all UK patients, consists of questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23, Body Image Scale, Hospital Anxiety and Depression Scale [HADS], and EQ-5D-3L) completed before randomisation, and at 1, 2, 5, and 10 years. The prespecified primary outcomes within this QOL substudy were global QOL, fatigue, physical function, chest wall symptoms, shoulder and arm symptoms, body image, and anxiety and depression. Data were analysed by intention to treat, using repeated mixed-effects methods. This trial is registered with the ISRCTN registry, number ISRCTN61145589. FINDINGS: Between Aug 4, 2006, and April 29, 2013, 1688 patients were enrolled internationally and randomly assigned to receive chest wall radiotherapy (n=853) or not (n=835). 989 (79%) of 1258 patients from 111 UK centres consented to participate in the QOL substudy (487 in the radiotherapy group and 502 in the no radiotherapy group), of whom 947 (96%) returned the baseline questionnaires and were included in the analysis (radiotherapy, n=471; no radiotherapy, n=476). At up to 2 years, chest wall symptoms were worse in the radiotherapy group than in the no radiotherapy group (mean score 14·1 [SD 15·8] in the radiotherapy group vs 11·6 [14·6] in the no radiotherapy group; effect estimate 2·17, 95% CI 0·40-3·94; p=0·016); however, there was an improvement in both groups between years 1 and 2 (visit effect -1·34, 95% CI -2·36 to -0·31; p=0·010). No differences were seen between treatment groups in arm and shoulder symptoms, body image, fatigue, overall QOL, physical function, or anxiety or depression scores. INTERPRETATION: Postmastectomy radiotherapy led to more local (chest wall) symptoms up to 2 years postrandomisation compared with no radiotherapy, but the difference between groups was small. These data will inform shared decision making while we await survival (trial primary endpoint) results. FUNDING: Medical Research Council, European Organisation for Research and Treatment of Cancer, Cancer Australia, Dutch Cancer Society, Trustees of Hong Kong and Shanghai Banking Corporation.