[Value-based healthcare in mental health care: a practical example]. / Waardegedreven zorg in de ggz: een praktijkvoorbeeld.

BACKGROUND: To promote quality improvement in Dutch mental health care, it is imperative to line up methods of quality improvement with daily care practice. In value-based healthcare the joint vision of medical professionals and patients is leading in the design and execution of care improvements. AIM: To demonstrate the value of value-based care. METHOD: Description of a practical example of the application of value based healthcare in mental healthcare, including a practical example of value-based improvement of patient care. RESULTS: A multidisciplinary improvement team was formed, consisting of patients and employees who were involved in the depression care pathway. The team determined important outcomes of care from the patient’s perspective, and successfully executed several improvement initiatives. CONCLUSION: The bottom-up approach of value-based healthcare is in line with day-to-day care practice and provides opportunities for effectively improving the quality of mental health care.

The diagnostic accuracy of local staging in colon cancer based on computed tomography (CT): evaluating the role of extramural venous invasion and tumour deposits.

PURPOSE: The shift from adjuvant to neoadjuvant treatment in colon cancer demands the radiological selection of patients for systemic therapy. The aim of this study was to evaluate the accuracy of the CT-based TNM stage and high-risk features, including extramural venous invasion (EMVI) and tumour deposits, in the identification of patients with histopathological advanced disease, currently considered for neoadjuvant treatment (T3-4 disease). METHODS: All consecutive patients surgically treated for non-metastatic colon cancer between January 2018 and January 2020 in a referral centre for colorectal cancer were identified retrospectively. All tumours were staged on CT according to the TNM classification system. Additionally, the presence of EMVI and tumour deposits on CT was evaluated. The histopathological TNM classification was used as reference standard. RESULTS: A total of 176 patients were included. Histopathological T3-4 colon cancer was present in 85.0% of the patients with CT-detected T3-4 disease. Histopathological T3-4 colon cancer was present in 96.4% of the patients with CT-detected T3-4 colon cancer in the presence of both CT-detected EMVI and CT-detected tumour deposits. Histopathological T0-2 colon cancer was present in 50.8% of the patients with CT-detected T0-2 disease, and in 32.4% of the patients without CT-detected EMVI and tumour deposits. CONCLUSION: The diagnostic accuracy of CT-based staging was comparable with previous studies. The presence of high-risk features on CT increased the probability of histopathological T3-4 colon cancer. However, a substantial part of the patients without CT-detected EMVI and tumour deposits was diagnosed with histopathological T3-4 disease. Hence, more accurate selection criteria are required to correctly identify patients with locally advanced disease.

Cardiac magnetic field map topology quantified by Kullback-Leibler entropy identifies patients with clinically suspected myocarditis.

Background: Myocarditis is a condition that can have severe adverse outcomes and lead to sudden cardiac death if remaining undetected. This study tested the capability of cardiac magnetic field mapping to detect patients with clinically suspected myocarditis. This could open up the way for rapid, non-invasive, and cost-effective screening of suspected cases before a gold standard assessment via endomyocardial biopsy. Methods: Historical cardiac magnetic field maps (n = 97) and data from a state-of-the-art magnetocardiography device (n = 30) were analyzed using the Kullback-Leibler entropy (KLE) for dimensionality reduction and topological quantification. Linear discriminant analysis was used to discern between patients with ongoing myocarditis and healthy controls. Results: The STT segment of a magnetocardiogram, i.e., the section between the end of the S wave and the end of the T wave, was best suited to discern both groups. Using a 250-ms excerpt from the onset of the STT segment gave a reliable classification between the myocarditis and control group for both historic data (sensitivity: 0.83, specificity: 0.85, accuracy: 0.84) and recent data (sensitivity: 0.69, specificity: 0.88, accuracy: 0.80) using the KLE to quantify the topology of the cardiac magnetic field map. Conclusion: The implementation based on KLE can reliably distinguish between clinically suspected myocarditis patients and healthy controls. We implemented an automatized feature selection based on LDA to replace the observer-dependent manual thresholding in previous studies.

Exploring aspects of self-reported emotional mental imagery in patients with bipolar disorder.

BACKGROUND AND OBJECTIVES: CBT for patients with bipolar disorder has modest effects. Across disorders, mental imagery has been used to update CBT to increase effectiveness. In order to enhance CBT for bipolar disorder with imagery techniques, research is needed into emotional imagery quality and, related appraisals of imagery and their relationships with mood instability and subsequent behaviour in bipolar disorder. METHODS: Patients with bipolar disorder (n = 106), unipolar depression (n = 51), creative imagery prone participants (n = 53) and participants without a history of a mood disorder (n = 135) completed the Dutch Imagery Survey (DImS), an online imagery survey, adapted from the Imagery Interview, assessing self-reported emotional imagery aspects. Imagery quality, appraisals and their self-perceived effects on emotion and behaviour were compared between groups. As unexpected differences within the bipolar group appeared, these were additionally explored. RESULTS: Imagery appraisals but not imagery quality discriminated between the patient groups and non-patient groups Imagery was perceived as an emotional amplifier in all groups, but this was specifically apparent in bipolar manic and bipolar depressed groups. Only in the bipolar group imagery was experienced to amplify behavioural tendencies. LIMITATIONS: Results need to be replicated using a larger sample of patients with BD who are currently manic or depressed. CONCLUSIONS: Not only quality of imagery, but especially appraisals associated with imagery are differentiating between imagery prone people with and without mood disorder. Imagery amplifies emotion in all groups, but only in those patients with bipolar disorder currently manic or depressed did this influence behaviour.

Comparing the effectiveness of imagery focussed cognitive therapy to group psychoeducation for patients with bipolar disorder: A randomised trial.

BACKGROUND: Bipolar disorder is a severe, chronic mental disorder. Treatment options are limited, with pharmacological approaches continuing to dominate. However, relapse rates remain high. Several adjunctive psychosocial interventions, mostly psychoeducation (PE) and cognitive behavioural therapy (CBT), have been trialled, but treatment innovation is still needed. In the past, brief group PE has proven as beneficial as longer individual CBT in reducing levels of depression and increasing self-management strategies. We compared the relative effectiveness of group PE to an imagery focussed cognitive behavioural therapy (ImCT). STUDY DESIGN: This was a randomised parallel group study with both daily and weekly measures. A total of 62 adult patients were randomly allocated to either ImCT or group PE. Daily, weekly and pre-and post-intervention measures were used to assess impact on (i) mood instability, (ii) overall levels of depression, anxiety and mania, and (iii) general functioning, hopelessness and imagery characteristics. A four-week baseline and 16-week follow-up period were included. RESULTS: Mood instability reduced in both conditions after intervention. Levels of mania, depression and anxiety also reduced in both conditions, but on the daily measures, depression and anxiety significantly more so in the ImCT condition. Compared with the PE condition, the ImCT condition additionally showed increased level of functioning, reduced hopelessness, and a decrease in intrusive, problematic imagery. LIMITATIONS: These findings need to be replicated in a larger trial. CONCLUSIONS: Findings suggest that ImCT is a promising new avenue for management of bipolar disorder, an area in which treatment development is urgently needed.

INFEXIT: Implementing vaginal disinfection prior to cesarean section.

OBJECTIVE: To evaluate the rate of implementation after adding vaginal disinfection to the cesarean section protocol and its effect on post cesarean infections and hospital readmissions. STUDY DESIGN: This is an intervention study where two groups were compared. Women the year before (n = 1384) and one year following (n = 1246) the addition of vaginal disinfection, with povidone-iodine 1% prior to the cesarean section, to the protocol. Primary outcome was the rate of implementation. Secondary outcomes were the rates of endometritis, wound infection and postoperative fever. With the effect expressed in the number of hospital readmissions. RESULTS: The implementation rate was 85.6%. Intention-to-treat analysis showed endometritis rates of 2.0% versus 1.1% (p = 0.07). For women with preoperative ruptured membranes there was a significant decrease in endometritis, from 3.4% to 1.3% (p = 0.02). Per-protocol analysis showed endometritis rates of 2.0% to 1.0% (p = 0.05). Women with ruptured membranes, 3.4% versus 1.3% (p = 0.02), and women who were in the second stage of labor, 4.7% versus 0.0% (p = 0.01), had a significant decrease in endometritis. For wound infection and postoperative fever rates were similar. The decrease of infections had a significant effect on hospital readmissions, 27 versus 10 (p = 0.04). CONCLUSION: The implementation of this quality improvement measure shows to be adequate as the vast majority of women undergoing a cesarean received vaginal disinfection. Vaginal disinfection showed a declining trend of endometritis and postoperative fever and for women with broken membranes prior to cesarean section the decrease in endometritis was significant. These beneficial effects have led to a statistical and clinically relevant decrease in hospital readmissions and thus cost reduction.

Neoadjuvant FOLFOXIRI prior to chemoradiotherapy for high-risk ("ugly") locally advanced rectal cancer: study protocol of a single-arm, multicentre, open-label, phase II trial (MEND-IT).

BACKGROUND: The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients. METHODS: This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life. DISCUSSION: This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04838496 , registered on 02-04-2021 Netherlands Trial Register: NL9790. PROTOCOL VERSION: Version 3 dd 11-4-2022.

Mind the gap: Patterns of red blood cell product usage in South Africa, 2014 - 2019.

BACKGROUND: A key component of any successful healthcare system is the availability of sufficient, safe blood products delivered in an equitable manner. South Africa (SA) has a two-tiered healthcare system with public and privately funded sectors. Blood utilisation data for both sectors are lacking. Evaluation of blood utilisation patterns in each healthcare sector will enable implementation of systems to bring about more equality. OBJECTIVES: To conduct a critical evaluation of red blood cell (RBC) product utilisation patterns at the South African National Blood Service (SANBS). METHODS: Operationally collected data from RBC requests submitted to SANBS blood banks for the period 1 January 2014 - 31 March 2019 were used to determine temporal RBC product utilisation patterns by healthcare sector. Demographic patterns were determined, and per capita RBC utilisation trends calculated. RESULTS: Of the 2 356 441 transfusion events, 65.9% occurred in the public and 34.1% in the private sector. Public sector patients were younger (median (interquartile range (IQR)) 33 (22 - 49) years) than in the private sector (median (IQR) 54 (37 - 68) years), and mainly female in both sectors (66.2% in the public sector and 53.4% in the private sector). Between 2014 and 2018, per capita RBC utilisation decreased from 11.9 to 11.0/1 000 population in the public sector, but increased from 34.8 to 38.2/1 000 population in the private sector. CONCLUSIONS: We confirmed distinctly different RBC utilisation patterns between the healthcare sectors in SA. Possible drivers for these differences may be healthcare access, differing patient populations and prescriber habits. Better understanding of these drivers may help inform equitable public health policy.

Taking therapeutic apheresis services to patients in South Africa: An eight year review of SANBS mobile therapeutic apheresis service, 2013-2020.

INTRODUCTION: A 20 year review of health and health care presents the multiple challenges faced by South Africans. Health and poverty is highlighted with 45% of population living on approximately US$ 2 per day and 10 million living on less than US$ 1 per day. Widening disparities in health care provision between public and private sector hospital services exist. The South African population includes the largest number of people living with HIV infection/AIDS of any country in the world, with a 70% estimate of 7.5 million people living with HIV on antiretroviral therapy. The South African National Blood Service provides a mixed model therapeutic apheresis service including mobile service and fixed-site therapeutic apheresis and an apheresis collection of hematopoietic stem cell (HPC-A) service. Therapeutic apheresis modalities offered by SANBS include plasmapheresis, red cell exchange, leukocyte and platelet reduction. In addition, collection of plasma, thrombocytes, mononuclear cells including CD34+ cells (HPCs) and granulocytes by apheresis for plasma and cellular therapies, and customised apheresis products for research purposes is offered. An operational database for the period 2013 to 2020 was reviewed to characterise the SANBS's mixed therapeutic apheresis service and HPC-A service from 2013 to 2020 in terms of patient numbers, patient demographics, patient procedures, therapeutic apheresis indication or diagnosis, therapeutic apheresis modality, hospital service type, and the American Society for Apheresis (ASFA) category of diagnosis. METHODS: A retrospective review of therapeutic apheresis patients referred to SANBS characterising patient numbers, patient demographics, patient procedures, therapeutic apheresis indication or diagnosis, therapeutic apheresis modality (Linz, 2017), hospital service type, and the ASFA category of diagnosis (Padmanabhan et al., 2019) for the period 01 January 2013 to 31 December 2020 was completed. Data is obtained from a SANBS operational routinely utilised to record patient procedure data. Patient procedure data is manually recorded by apheresis nurses and indexed on to the operational database, with both processes audited. The review period is a convenience sample. Storage of the database and access of the operational database is in compliance with the Protection of Personal Information Act (Government Gazette, 2013). Therapeutic apheresis modalities analysed include Plasmapheresis, Red Cell Exchange, Leukopheresis, Thrombocytapheresis, Lymphocyte collection, Granulocyte collection, Haematopoietic stem cell collection by apheresis and customised apheresis products for research purposes. Customised apheresis products for research purposes is excluded from this review. Descriptive statistics is used. RESULTS: For the review period, 2,485 unique patients with 120 unique indications as recorded by referring clinicians received 13,518 procedures involving 7 therapeutic apheresis modalities at 78 hospitals (21 public sector and 57 private sector) and at 3 SANBS blood donor centres in 7 provinces of South Africa. The age range of patients serviced is 4 months to 90 years (median = 39.5 years) (figure 1), 91% by procedure count was for patients 21 years of age or older, 62% were female, with 10,783 (79.6%) procedures performed in public sector hospitals. In all patients, the most common indications was plasmapheresis for thrombotic thromobocytopaenic purpura (52.5% of cumulative procedures), HPC-A for multiple myeloma (7.86%) and Antibody-mediated kidney transplant rejection (4.90%). Plasmapheresis was the most common therapeutic apheresis modality used (82.5% of cumulative procedures) followed by HPC-A (13.7%) and leukoreduction (3.39%). A range of indications for plasmapheresis (n = 65) and HPC-A (n = 41) were observed. Red cell exchange procedures was performed for patients with severe malaria and sickle cell disease indications. For leukoreduction indications, all patients were adults managed in public sector facilities and all were symptomatic. The most common indications were Chronic Myelogenous Leukemia, Chronic Lymphocytic Leukaemia and Multiple Myeloma. A pooled, total white cell count average of 457 × 109/L (range 141-689 × 109/L) prior to first procedure. Despite complex challenges for a national mixed model service, successful patient outcomes in emergent indications such as TTP (Louw et al., 2018; Swart et al., 2019) and engraftment post HPC-A in HSCT in multiple centres (Glatt, personal communication) are reported. CONCLUSION: The review confirms that apheresis medicine is increasingly used in South Africa in patients in both public and private sector, with the most common modalities being plasmapheresis, HPC-A and leukoreduction. Patients with HIV-associated TTP is the most commonly referred patient in both paediatric and adult patients and this is anticipated to continue. A growing HSCT transplant network capacity in South Africa is augmented through the mixed model mobile and fixed-site therapeutic apheresis services, including a mobile HPC-A service. The increasing number of HPC-A is a trend towards increasing numbers of patients support to HSCT for both adults and paediatric patients in private and public sector hospitals.

Improved response rate in patients with prognostically poor locally advanced rectal cancer after treatment with induction chemotherapy and chemoradiotherapy when compared with chemoradiotherapy alone: A matched case-control study.

INTRODUCTION: The addition of induction chemotherapy (ICT) to neoadjuvant chemoradiotherapy (CRT) has the potential to improve outcomes in patients with locally advanced rectal cancer (LARC). However, patient selection is essential to prevent overtreatment. This study compared the complete response (CR) rate after treatment with and without ICT of LARC patients with prognostically poor characteristics. METHODS: All LARC patients who were treated with neoadjuvant CRT, whether or not preceded by ICT, and who underwent surgery or were considered for a wait-and-see strategy between January 2016 and March 2020 in the Catharina Hospital Eindhoven, were retrospectively selected. LARC was defined as any T4 tumour, or a T2/T3 tumour with extramural venous invasion and/or tumour deposits and/or N2 lymph node status, and/or mesorectal fascia involvement (T3 tumours only). Case-control matching was performed based on the aforementioned characteristics. RESULTS: Of 242 patients, 178 (74%) received CRT (CRT-group) and 64 patients (26%) received ICT followed by CRT (ICT-group). In the ICT-group, 3 patients (5%) did not receive the minimum of three cycles. In addition, in this selected cohort, compliance with radiotherapy was 100% in the ICT-group and 97% in the CRT-group. The CR rate was 30% in the ICT-group and 15% in the CRT-group (p = 0.011). After case-control matching, the CR rate was 28% and 9%, respectively (p = 0.013). CONCLUSION: Treatment including ICT seemed well tolerated and resulted in a high CR rate. Hence, this treatment strategy may facilitate organ preservation and improve survival in LARC patients with prognostically poor characteristics.

Image qualities and mood variability: Evaluating the utility of an imagery survey for bipolar disorder.

OBJECTIVE: Imagery appears to play an important role in mood variability, a core symptom of patients suffering from bipolar disorder. The present study aimed to explore the validity and reliability of an online self-report measure of imagery, the Dutch Imagery Survey (DImS). The DImS is an adaptation of the Imagery interview used in research on imagery in mental disorders. The present study additionally explored the ability of the DImS to detect relationships between self-reported imagery and subsequent mood and subsequent behaviour. METHOD: 135 students completed the DImS and additional mental imagery and mood questionnaires. For re-test reliability, 42 students completed the survey again within two days. RESULTS: Internal consistencies and test-retest scores of the five scales of the DImS were reasonable. Imagery Quality correlated with Emotions, and to a lesser degree with Behaviour. Positive Appraisals correlated with Positive Emotions, Negative Appraisals with Negative Emotions, and Positive appraisals with Behaviour. Frequency of Imagery, Imagery Quality and Positive Appraisals correlated with elevated mood. Imagery Quality and Negative Appraisals correlated with low mood. The DImS took approximately 15 min to complete. LIMITATIONS: Re-test reliability was limited due to participants changing their dominant image. Results need to be replicated in a clinical sample. CONCLUSIONS: Psychometric findings with the DImS appeared reasonable and consistent and showed that, in line with other recent studies, imagery is related to current mood and to both self-perceived emotion and subsequent behaviour. These findings suggested that the DImS is suitable to study the role of imagery in bipolar mood variability.

International Liaison Committee on Resuscitation: COVID-19 consensus on science, treatment recommendations and task force insights.

Consensus on Science and Treatment recommendations aim to balance the benefits of early resuscitation with the potential for harm to care providers during the COVID-19 pandemic. Chest compressions and cardiopulmonary resuscitation have the potential to generate aerosols. During the current COVID-19 pandemic lay rescuers should consider compressions and public-access defibrillation. Lay rescuers who are willing, trained and able to do so, should consider providing rescue breaths to infants and children in addition to chest compressions. Healthcare professionals should use personal protective equipment for aerosol generating procedures during resuscitation and may consider defibrillation before donning personal protective equipment for aerosol generating procedures.

A cognitive behavioural group therapy for bipolar disorder using daily mood monitoring.

BACKGROUND AND AIM: This study investigated the effects of group cognitive behavioural therapy (CBT) for patients with bipolar disorder. The development of CBT for this disorder is relatively under-explored. METHOD: Participants with bipolar I or II disorder were treated with group CBT in addition to treatment as usual. The effectiveness of the protocol was explored through sequence analysis of daily mood monitoring prior to, during and after the intervention. Also, a repeated measures design was used assessing symptomatology, dysfunctional attitudes, sense of mastery, psychosocial functioning, and quality of life at start and end of intervention, and at follow-up 2 and 12 months later. RESULTS: The results indicate that variation in mood states diminished over the course of the intervention. Also, there was a change from depressive states to more euthymic states. Greater number of reported lifetime depressive episodes was associated with greater diversity of mood states. There was an increase in overall psychosocial functioning and self-reported psychological health following the intervention. Improvement continued after treatment ended until follow-up at 2 months, and measured 1 year later, for outcomes representing depression, general psychosocial functioning and self-reported psychological health. Due to small sample size and the lack of a control group the results are preliminary. CONCLUSIONS: The results of this pilot study suggest that both offering CBT in group interventions and sequence analysis of time series data are helpful routes to further explore when improving standard CBT interventions for patients suffering from bipolar disorder.

Towards the future of blood transfusion - the South African National Blood Service's perspectives on cellular therapeutic services and products.

Blood transfusion services are the cornerstone of the healthcare delivery system, and need to stay abreast of advances in technology to ensure relevance to the needs of the country. In this review, we examine the current status of blood transfusion systems and discuss their possible future role in cellular therapies.

Phylogenetic and kinematic constraints on avian flight signals.

Many birds vocalize in flight. Because wingbeat and respiratory cycles are often linked in flying vertebrates, birds in these cases must satisfy the respiratory demands of vocal production within the physiological limits imposed by flight. Using acoustic triangulation and high-speed video, we found that avian vocal production in flight exhibits a largely phasic and kinematic relationship with the power stroke. However, the sample of species showed considerable flexibility, especially those from lineages known for vocal plasticity (songbirds, parrots and hummingbirds), prompting a broader phylogenetic analysis. We thus collected data from 150 species across 12 avian orders and examined the links between wingbeat period, flight call duration and body mass. Overall, shorter wingbeat periods, controlling for ancestry and body mass, were correlated with shorter flight call durations. However, species from vocal learner lineages produced flight signals that, on average, exceeded multiple phases of their wingbeat cycle, while vocal non-learners had signal periods that were, on average, closer to the duration of their power stroke. These results raise an interesting question: is partial emancipation from respiratory constraints a necessary step in the evolution of vocal learning or an epiphenomenon? Our current study cannot provide the answer, but it does suggest several avenues for future research.

Proton-dynamic therapy following photosensitiser activation by accelerated protons demonstrated through fluorescence and singlet oxygen production.

We demonstrate excitation of photosensitisers (PSs) by accelerated protons to produce fluorescence and singlet oxygen. Their fluorescence follows a pattern similar to the proton energy loss in matter, while proton-derived fluorescence spectra match the photon-induced spectra. PSs excited in dry gelatin exhibit enhanced phosphorescence, suggesting an efficient PSs triplet state population. Singlet oxygen measurements, both optically at ~1270 nm and through the photoproduct of protoporphyrin IX (PpIX), demonstrate cytotoxic singlet oxygen generation by proton excitation. The singlet oxygen-specific scavenger 1,4-diazabicyclo[2.2.2]octane (DABCO) abrogates the photoproduct formation under proton excitation, but cannot countermand the overall loss of PpIX fluorescence. Furthermore, in two cell lines, M059K and T98G, we observe differential cell death upon the addition of the PS cercosporin, while in U87 cells we see no effect at any proton irradiation dose. Our results pave the way for a novel treatment combining proton therapy and "proton-dynamic therapy" for more efficient tumour eradication.