Proton Beam Therapy for Early Breast Cancer: A Systematic Review and Meta-analysis of Clinical Outcomes.

PURPOSE: Adjuvant proton beam therapy (PBT) is increasingly available to patients with breast cancer. It achieves better planned dose distributions than standard photon radiation therapy and therefore may reduce the risks. However, clinical evidence is lacking. METHODS AND MATERIALS: A systematic review of clinical outcomes from studies of adjuvant PBT for early breast cancer published in 2000 to 2022 was undertaken. Early breast cancer was defined as when all detected invasive cancer cells are in the breast or nearby lymph nodes and can be removed surgically. Adverse outcomes were summarized quantitatively, and the prevalence of the most common ones were estimated using meta-analysis. RESULTS: Thirty-two studies (1452 patients) reported clinical outcomes after adjuvant PBT for early breast cancer. Median follow-up ranged from 2 to 59 months. There were no published randomized trials comparing PBT with photon radiation therapy. Scattering PBT was delivered in 7 studies (258 patients) starting 2003 to 2015 and scanning PBT in 22 studies (1041 patients) starting 2000 to 2019. Two studies (123 patients) starting 2011 used both PBT types. For 1 study (30 patients), PBT type was unspecified. Adverse events were less severe after scanning than after scattering PBT. They also varied by clinical target. For partial breast PBT, 498 adverse events were reported (8 studies, 358 patients). None were categorized as severe after scanning PBT. For whole breast or chest wall ± regional lymph nodes PBT, 1344 adverse events were reported (19 studies, 933 patients). After scanning PBT, 4% (44/1026) of events were severe. The most prevalent severe outcome after scanning PBT was dermatitis, which occurred in 5.7% (95% confidence interval, 4.2-7.6) of patients. Other severe adverse outcomes included infection, pain, and pneumonitis (each ≤1%). Of the 141 reconstruction events reported (13 studies, 459 patients), the most prevalent after scanning PBT was prosthetic implant removal (34/181, 19%). CONCLUSIONS: This is a quantitative summary of all published clinical outcomes after adjuvant PBT for early breast cancer. Ongoing randomized trials will provide information on its longer-term safety compared with standard photon radiation therapy.

Adjuvant and neoadjuvant breast cancer treatments: A systematic review of their effects on mortality.

BACKGROUND: Adjuvant and neoadjuvant breast cancer treatments can reduce breast cancer mortality but may increase mortality from other causes. Information regarding treatment benefits and risks is scattered widely through the literature. To inform clinical practice we collated and reviewed the highest quality evidence. METHODS: Guidelines were searched to identify adjuvant or neoadjuvant treatment options recommended in early invasive breast cancer. For each option, systematic literature searches identified the highest-ranking evidence. For radiotherapy risks, searches for dose-response relationships and modern organ doses were also undertaken. RESULTS: Treatment options recommended in the USA and elsewhere included chemotherapy (anthracycline, taxane, platinum, capecitabine), anti-human epidermal growth factor 2 therapy (trastuzumab, pertuzumab, trastuzumab emtansine, neratinib), endocrine therapy (tamoxifen, aromatase inhibitor, ovarian ablation/suppression) and bisphosphonates. Radiotherapy options were after breast conserving surgery (whole breast, partial breast, tumour bed boost, regional nodes) and after mastectomy (chest wall, regional nodes). Treatment options were supported by randomised evidence, including > 10,000 women for eight treatment comparisons, 1,000-10,000 for fifteen and < 1,000 for one. Most treatment comparisons reduced breast cancer mortality or recurrence by 10-25%, with no increase in non-breast-cancer death. Anthracycline chemotherapy and radiotherapy increased overall non-breast-cancer mortality. Anthracycline risk was from heart disease and leukaemia. Radiation-risks were mainly from heart disease, lung cancer and oesophageal cancer, and increased with increasing heart, lung and oesophagus radiation doses respectively. Taxanes increased leukaemia risk. CONCLUSIONS: These benefits and risks inform treatment decisions for individuals and recommendations for groups of women.

The use of Lean Methodology to reduce personal protective equipment wastage in children undergoing congenital cardiac surgery, during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has compounded many existing healthcare delivery challenges including long waiting lists and cost containment. New challenges have arisen, such as demand on supply of personal protective equipment (PPE) and the implications of social distancing on staff, patients, and their families. Despite the pandemic, the need to deliver safe, urgent congenital cardiac surgery has remained. OBJECTIVE: To demonstrate how Lean methodology can improve PPE supply chain demand and reduce staff exposure to children with unknown SARS-CoV-2 status undergoing congenital cardiac surgery, during the COVID-19 pandemic. METHODS: We implemented the define, measure, analyze, improve, and control method (DMAIC) and Value Stream Maps to eliminate waste steps during testing for SARS-CoV-2 for children undergoing congenital cardiac surgery. RESULTS: Following a 3-week period of implementation of this new value stream map, we reduced PPE set usage from 13 to 1 per patient, resulting in an annual saving of over €36,000 and reducing single-use plastic waste by nearly 70 000 pieces per annum. We reduced numbers of staff exposed to patients with an unknown SARS-CoV-2 status from 13 to 1. CONCLUSION: The use of Lean methodology can reduce waste of PPE and plastic, resulting in cost savings, while reducing staff exposure when testing patients with congenital cardiac disease for SARS-CoV-2. By preventing admission of SARS-CoV-2-positive patients, we can reduce use of isolation beds and prevent cancellation of surgery, improving patient flow and departmental efficiency. Other departments in our institution are implementing similar admission pathways to allow surgical services to restart during the ongoing pandemic.

The effect of dexmedetomidine on motor-evoked potentials during pediatric posterior spinal fusion surgery: a retrospective case-control study.

PURPOSE: Motor-evoked potentials (MEPs) are frequently used in pediatric posterior spinal fusion surgery (PSFS) to detect spinal cord ischemia. Dexmedetomidine is increasingly being used as an adjunct to total intravenous anesthesia, but its effect on MEP amplitude has been variably reported. The purpose of this study was to evaluate the effect of an infusion of dexmedetomidine on the amplitude of MEPs. METHODS: We performed a retrospective case-control study of 30 pediatric patients who received a 0.5 µg·kg-1·hr-1 infusion of dexmedetomidine, ten patients who received 0.3 µg·kg-1·hr-1 dexmedetomidine, and 30 control patients who did not receive dexmedetomidine during PSFS. Two neurophysiologists reviewed the MEP amplitudes in six muscle groups at three time points: when the patient was turned prone (baseline; T1), one hour after incision (T2), and after exposure of the spine but before insertion of the first screw (T3). RESULTS: In all muscles tested, the mean MEP amplitude was reduced by T3 when dexmedetomidine was infused at 0.5 µg·kg-1·hr-1. The greatest reduction from baseline MEP amplitude was 829 µV (95% confidence interval, 352 to 1230; P < 0.001) seen in first right dorsus interosseous. When dexmedetomidine was infused at 0.3 µg·kg-1·hr-1, there was a significant reduction in MEP amplitude in four of the six muscles tested at T3 compared with the control group. CONCLUSIONS: Dexmedetomidine at commonly used infusion rates of 0.3 µg·kg-1·hr-1 or 0.5 µg·kg-1·hr-1 causes a significant decrease in MEP amplitude during pediatric PSFS. We suggest that dexmedetomidine should be avoided in children undergoing PSFS so as not to confuse the interpretation of this important neurophysiological monitor.

RéSUMé: OBJECTIF: Les potentiels évoqués moteurs (PEM) sont fréquemment utilisés lors de chirurgies de fusion spinale postérieure chez l'enfant afin de détecter une ischémie de la moelle épinière. La dexmédétomidine est de plus en plus utilisée comme adjuvant à l'anesthésie intraveineuse totale, mais son effet sur l'amplitude des PEM n'a été rapporté que de façon variable. L'objectif de cette étude était d'évaluer l'effet d'une perfusion de dexmédétomidine sur l'amplitude des PEM. MéTHODE: Pendant une chirurgie de fusion spinale postérieure, nous avons réalisé une étude cas témoins rétrospective auprès de 30 patients pédiatriques ayant reçu une perfusion 0,5 µg·kg−1·h−1 de dexmédétomidine, 10 patients ayant reçu 0,3 µg·kg−1·h−1 de dexmédétomidine, et 30 patients témoins n'ayant pas reçu de dexmédétomidine. Deux neurophysiologistes ont passé en revue les amplitudes des PEM dans six groupes musculaires à trois moments de la chirurgie : lorsque le patient a été tourné sur le ventre (valeur de base; T1), une heure après l'incision (T2), et après l'exposition de la colonne mais avant l'insertion de la première vis (T3). RéSULTATS: Dans tous les muscles testés, l'amplitude moyenne des PEM était réduite à T3 lorsque la dexmédétomidine était perfusée à 0,5 µg·kg−1·h−1. La plus grande réduction par rapport à l'amplitude de base des PEM était de 829 µV (intervalle de confiance 95 %, 352 à 1230; P < 0,001) et a été observée au niveau du premier interosseux dorsal. Lorsque la dexmédétomidine était perfusée à 0,3 µg·kg−1·h−1, une réduction significative de l'amplitude des PEM a été observée dans quatre des six muscles testés à T3 par rapport au groupe témoin. CONCLUSION: La dexmédétomidine, administrée à des taux de perfusion fréquemment utilisés de 0,3 µg·kg−1·h−1 ou 0,5 µg·kg−1·h−1, a entraîné une réduction significative de l'amplitude des PEM pendant une chirurgie de fusion spinale postérieure chez l'enfant. Nous proposons d'éviter l'administration de dexmédétomidine chez les enfants devant subir une chirurgie de fusion spinale postérieure afin de ne pas brouiller l'interprétation de ce moniteur neurophysiologique important.

Proficiency-based progression training: an 'end to end' model for decreasing error applied to achievement of effective epidural analgesia during labour: a randomised control study.

BACKGROUND: Training procedural skills using proficiency-based progression (PBP) methodology has consistently resulted in error reduction. We hypothesised that implementation of metric-based PBP training and a valid assessment tool would decrease the failure rate of epidural analgesia during labour when compared to standard simulation-based training. METHODS: Detailed, procedure-specific metrics for labour epidural catheter placement were developed based on carefully elicited expert input. Proficiency was defined using criteria derived from clinical performance of experienced practitioners. A PBP curriculum was developed to train medical personnel on these specific metrics and to eliminate errors in a simulation environment.Seventeen novice anaesthetic trainees were randomly allocated to undergo PBP training (Group P) or simulation only training (Group S). Following training, data from the first 10 labour epidurals performed by each participant were recorded. The primary outcome measure was epidural failure rate. RESULTS: A total of 74 metrics were developed and validated. The inter-rater reliability (IRR) of the derived assessment tool was 0.88. Of 17 trainees recruited, eight were randomly allocated to group S and six to group P (three trainees did not complete the study). Data from 140 clinical procedures were collected. The incidence of epidural failure was reduced by 54% with PBP training (28.7% in Group S vs 13.3% in Group P, absolute risk reduction 15.4% with 95% CI 2% to 28.8%, p=0.04). CONCLUSION: Procedure-specific metrics developed for labour epidural catheter placement discriminated the performance of experts and novices with an IRR of 0.88. Proficiency-based progression training resulted in a lower incidence of epidural failure compared to simulation only training. TRIAL REGISTRATION NUMBER: NCT02179879. NCT02185079; Post-results.

Tracheostomy as a Comfort Measure in Children With Life-Limiting Conditions.

Palliative care for children who can expect only a short life has expanded over the last decade. Greater understanding of the measures required to ensure comfort and acceptable quality of life within the critical care environment has grown in tandem. Some more invasive interventions may be considered a "step too far" by some practitioners, including feeding gastrostomy, contracture release, and tracheostomy. Tracheostomy can facilitate a number of measures, which may enhance the brief life of the child and their family. However, tracheostomy is associated with some challenges, which may make it less suitable for some families. We discuss 3 cases where this intervention was carried out.

Rivastigmine for Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is the commonest cause of dementia affecting older people. One of the therapeutic strategies aimed at ameliorating the clinical manifestations of Alzheimer's disease is to enhance cholinergic neurotransmission in relevant parts of the brain by the use of cholinesterase inhibitors to delay the breakdown of acetylcholine released into synaptic clefts. Tacrine, the first of the cholinesterase inhibitors to undergo extensive trials for this purpose, was associated with significant adverse effects including hepatotoxicity. Other cholinesterase inhibitors, including rivastigmine, with superior properties in terms of specificity of action and low risk of adverse effects, have now been introduced. Rivastigmine has received approval for use in 60 countries including all member states of the European Union and the USA. OBJECTIVES: To determine the clinical efficacy and safety of rivastigmine for patients with dementia of Alzheimer's type. SEARCH STRATEGY: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on 27 March 2008 using the terms: Rivastigmine OR exelon OR ENA OR "SDZ ENA 713" . The CDCIG Specialized Register contains records from all major health care databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many clinical trials registries and grey literature sources. SELECTION CRITERIA: All unconfounded, double-blind, randomized trials in which treatment with rivastigmine was administered to patients with dementia of the Alzheimer's type for more than two weeks and its effects compared with those of placebo in a parallel group of patients. DATA COLLECTION AND ANALYSIS: One reviewer (JSB) applied study selection criteria, assessed the quality of studies and extracted data. MAIN RESULTS: Nine trials, involving 4775 participants, were included in the analyses. Use of rivastigmine in high doses was associated with statistically significant benefits on several measures. High-dose rivastigmine (6 to 12 mg daily) was associated with a two-point improvement in cognitive function on the ADAS-Cog score compared with placebo (weighted mean difference -1.99, 95% confidence interval -2.49 to -1.50, on an intention-to-treat basis) and a 2.2 point improvement in activities of daily living assessed on the Progressive Deterioration Scale (weighted mean difference -2.15, 95% confidence interval -3.16 to -1.13, on an intention-to-treat basis) at 26 weeks. At lower doses (4 mg daily or lower) differences were in the same direction but were statistically significant only for cognitive function. There were statistically significantly higher numbers of events of nausea, vomiting, diarrhoea, anorexia, headache, syncope, abdominal pain and dizziness among patients taking high-dose rivastigmine than among those taking placebo. There was some evidence that adverse events might be less common with more frequent, smaller doses of rivastigmine. The 2008 update includes a new study testing two types of rivastigmine transdermal patch, one delivering a higher dose than previously tested (17.4 mg/day) and a smaller patch delivering 9.6 mg/day. The efficacy of the smaller patch was not significantly different compared with the capsules of similar daily dose, but was associated with significantly fewer adverse events of nausea, vomiting, dizziness and asthenia. The efficacy of the larger patch was not significantly different compared with the smaller patch, but the smaller patch was associated with significantly fewer adverse events of nausea, vomiting, weight loss and dizziness. There appears to be advantages associated with the smaller patch compared with both the higher dose patch and the 6-12 mg/day capsules. AUTHORS' CONCLUSIONS: Rivastigmine appears to be beneficial for people with mild to moderate Alzheimer's disease. In comparisons with placebo, improvements were seen in the rate of decline of cognitive function, activities of daily living, and severity of dementia with daily doses of 6 to 12 mg. Adverse events were consistent with the cholinergic actions of the drug. A transdermal patch has been tested in one trial, and there is evidence that the lower dose smaller patch is associated with fewer side effects than the capsules or the higher dose larger patch and has comparable efficacy to both. This review has not examined economic data.