Post-COVID health policy responses to healthcare workforce capacities: A comparative analysis of health system resilience in six European countries.

A cross countries in Europe, health policy is seeking to adapt to the post-pandemic 'permacrisis', where high demands on the healthcare workforce and shortages continue and combine with climate change, and war. The success of these efforts depends on the capacities of the healthcare workforce. This study aims to compare health policy responses to strengthen the capacities of the healthcare workforce and to explore the underpinning dynamics between health systems, policy actors and health policies. The study draws on a qualitative, comparative analysis of Austria, the Czech Republic, Denmark, Germany, Italy and the Netherlands. The findings suggest that policy responses at the national level focused on hospitals and absorptive capacities, while policy responses at local/regional levels also included general practice and adaptive capacities. There were only few examples of policies directed at transformative capacities. The underling dynamics were shaped by health systems, where individual parts are closely connected, by embeddedness in specific service delivery and areas, and by power dynamics. In conclusion, sub-national health policy responses emerge as key to effective responses to the post-pandemic permacrisis, where health professions are central policy actors. Sub-national health policy responses build on existing power relations, but also have the potential to transcend these power relations.

Comparing Health Workforce Policy during a Major Global Health Crisis: A Critical Conceptual Debate and International Empirical Investigation.

BACKGROUND: The health workforce is central to healthcare systems and population health, but marginal in comparative health policy. This study aims to highlight the crucial relevance of the health workforce and contribute comparative evidence to help improve the protection of healthcare workers and prevention of inequalities during a major public health crisis. METHODS: Our integrated governance framework considers system, sector, organizational and socio-cultural dimensions of health workforce policy. The COVID-19 pandemic serves as the policy field and Brazil, Canada, Italy, and Germany as illustrative cases. We draw on secondary sources (literature, document analysis, public statistics, reports) and country expert information with a focus on the first COVID-19 waves until the summer of 2021. RESULTS: Our comparative investigation illustrates the benefits of a multi-level governance approach beyond health system typologies. In the selected countries, we found similar problems and governance gaps concerning increased workplace stress, lack of mental health support, and gender and racial inequalities. Health policy across countries failed to adequately respond to the needs of HCWs, thus exacerbating inequalities during a major global health crisis. CONCLUSIONS: Comparative health workforce policy research may contribute new knowledge to improve health system resilience and population health during a crisis.

Health system resilience and health workforce capacities: Comparing health system responses during the COVID-19 pandemic in six European countries.

BACKGROUND: The health workforce is a key component of any health system and the present crisis offers a unique opportunity to better understand its specific contribution to health system resilience. The literature acknowledges the importance of the health workforce, but there is little systematic knowledge about how the health workforce matters across different countries. AIMS: We aim to analyse the adaptive, absorptive and transformative capacities of the health workforce during the first wave of the COVID-19 pandemic in Europe (January-May/June 2020), and to assess how health systems prerequisites influence these capacities. MATERIALS AND METHODS: We selected countries according to different types of health systems and pandemic burdens. The analysis is based on short, descriptive country case studies, using written secondary and primary sources and expert information. RESULTS AND DISCUSSION: Our analysis shows that in our countries, the health workforce drew on a wide range of capacities during the first wave of the pandemic. However, health systems prerequisites seemed to have little influence on the health workforce's specific combinations of capacities. CONCLUSION: This calls for a reconceptualisation of the institutional perquisites of health system resilience to fully grasp the health workforce contribution. Here, strengthening governance emerges as key to effective health system responses to the COVID-19 crisis, as it integrates health professions as frontline workers and collective actors.

Interregional Patient Mobility in the Italian NHS: A Case of Badly-Managed Decentralization Comment on "Regional Incentives and Patient Cross-Border Mobility: Evidence From the Italian Experience".

The article by Brenna and Spandonaro on interregional mobility for acute hospital care in Italy raises important issues concerning social and territorial equity in a healthcare system. Based on Regions and private providers' strategic behavior, the hypothesis adopted to explain patient cross-border mobility (CBM), demonstrated by statistical analysis, may be further explored using qualitative methods. In order to reduce CBM, the central government needs to play a more active role in coordination, even in a highly decentralized National Health Service (NHS).

Conservative treatment of breast ductal carcinoma in situ: results of an Italian multi-institutional retrospective study.

BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) has increased markedly in recent decades. In the past, mastectomy was the primary treatment for patients with DCIS, but as with invasive cancer, breast-conserving surgery followed by radiation therapy (RT) has become the standard approach. We present the final results of a multi-institutional retrospective study of an Italian Radiation Oncology Group for the study of conservative treatment of DCIS, characterized by a very long period of accrual, from February 1985 to March 2000, and a median follow-up longer than 11 years. METHODS: A collaborative multi-institutional study was conducted in Italy in 10 Radiation Oncology Departments. A consecutive series of 586 women with DCIS histologically confirmed, treated between February 1985 and March 2000, was retrospectively evaluated. Median age at diagnosis was 55 years (range: 29-84); 32 patients were 40 years old or younger. All women underwent conservative surgery followed by whole breast RT. Irradiation was delivered to the entire breast, for a median total dose of 50 Gy; the tumour bed was boosted in 295 cases (50%) at a median dose of 10 Gy. RESULTS: After a median follow-up of 136 months (range: 16-292 months), 59/586 patients (10%) experienced a local recurrence: invasive in 37 cases, intraductal in 20 and not specified in two. Salvage mastectomy was the treatment of choice in 46 recurrent patients; conservative surgery in 10 and it was unknown in three patients. The incidence of local recurrence was significantly higher in women younger than 40 years (31.3%) (p= 0.0009). Five patients developed distant metastases. Furthermore 40 patients developed a contralateral breast cancer and 31 a second primary tumour in a different site. The 10-year actuarial overall survival (OS) was 95.5% and the 10-year actuarial disease-specific survival (DSS) was 99%. CONCLUSIONS: Our results are consistent with those reported in the literature. In particular it has been defined the importance of young age (40 years or less) as a relevant risk factor for local recurrence. This retrospective multi-institutional Italian study confirms the long term efficacy of breast conserving surgery with RT in women with DCIS.

Clinically-staged T3N0 rectal cancer: is preoperative chemoradiotherapy the optimal treatment?

BACKGROUND: Preoperative chemoradiotherapy has been widely adopted as the standard of care for stage II-III rectal cancers. However, patients with T3N0 lesions had been shown to have a better prognosis than other categories of locally advanced tumor. Thus, neoadjuvant chemoradiation is likely to be overtreatment in this subgroup of patients. Nevertheless, the low accuracy rate of preoperative staging techniques for detection of node-negative tumors does not allow to check this hypothesis. We analyzed a group of patients with cT3N0 low rectal cancer who underwent neoadjuvant chemoradiotherapy with the purpose of evaluating the incidence of metastatic nodes in the resected specimens. METHODS: Between January 2002 and February 2008, 100 patients with low rectal cancer underwent clinical staging by means of endorectal ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging. All patients received preoperative 5-fluorouracil-based chemoradiotherapy and surgical resection with curative aim. RESULTS: Of 100 patients with locally advanced rectal cancer, 32 were clinically staged as T3N0M0. Pathological analysis showed the presence of lymph node metastases in nine patients (28%) (node-positive group). In the remaining 23 cases, clinical N stage was confirmed at pathology (node-negative group). Node-positive and node-negative groups differ only in the number of ypT3 tumors (P < .01). CONCLUSIONS: Our results indicate that immediate surgery for patients with cT3N0 rectal cancer represents an undertreatment risk in at least 28% of cases, making necessary the use of postoperative chemoradiotherapy. Preoperative chemoradiotherapy should be the therapy of choice on the grounds of the principle that overtreatment is less hazardous than undertreatment for cT3N0 rectal cancers.

32P brachytherapy in the treatment of complex Cypher in-stent restenosis.

Treatment of in-stent restenosis after implantation of a drug-eluting stent is a critical issue. We provide the first report of the use of intravascular radiation therapy for this purpose in a 73-year-old diabetic patient stented for small-vessel bifurcation; treatment of Cypher diffuse in-stent restenosis with (32)P brachytherapy proved successful at clinical and angiographic follow-up at 7 months. This finding should encourage systematic studies on the safety and efficacy of IRT in this problematic setting.

Long-term clinical and angiographic outcome of patients with occlusive in-stent restenosis treated with (32P) beta-brachytherapy.

The objective of this study was to determine the safety and efficacy of (32)P beta-brachytherapy in totally occlusive in-stent restenosis (ISR). Patients with occlusive ISR were generally excluded from the randomized clinical trials on intracoronary brachytherapy (utilizing either gamma- or beta-sources) that have shown reductions in restenosis rate and need for revascularization procedures. We analyzed short- and long-term effects of (32)P beta-brachytherapy (20 Gy) in 27 patients (28 lesions) with occlusive ISR and 84 (99 lesions) patients with nonocclusive high-risk ISR. The primary outcome measure was frequency of in-lesion angiographic binary restenosis at 7 months. Secondary endpoints were rates of major adverse cardiac events (MACE), target vessel revascularization (TVR), clinically driven TVR, and target lesion revascularization (TLR). (32)P beta-brachytherapy was feasible and safe and provided similar postprocedural angiographic results in the two clinically comparable groups. However, the 7-month binary restenosis rate was higher in the occlusive group, as were the MACE and late total occlusion rates. Multivariate logistic analysis of the overall population indicated occlusive pattern to be the only independent predictor of angiographic restenosis. In both groups, recurrent lesions most often showed a focal pattern with significant reduction of length. Although safe and effective in high-risk ISR, (32)P brachytherapy at 20 Gy does not appear to be sufficient to avoid long-term restenosis in patients with occlusive lesions. Further studies should determine the most suitable source and dosage of brachytherapy for patients with occlusive ISR.

Predictors of 32P beta brachytherapy failure in patients with high-risk in-stent restenosis.

BACKGROUND: The effectiveness of coronary radiation therapy for the treatment of in-stent restenosis (ISR) has been established in several randomized clinical trials. The efficacy of this treatment in the general population is less well established. METHODS AND MATERIALS: We report our experience in 118 consecutive patients with nonselected high-risk ISR who had undergone successful percutaneous coronary intervention and brachytherapy with (32)P beta-irradiation and who were prospectively enrolled in a quantitative angiographic and clinical follow-up protocol at 7 months after the index procedure. The aim of this study was to investigate the independent predictor of angiographic restenosis after (32)P brachytherapy treatment. RESULTS: Of the patients, 28.8% were diabetics. The mean lesion and mean radiated lengths were, respectively, 30.1 +/- 17.2 and 43.8 +/- 16.9 mm. The ISR pattern was diffuse in 96% of the treated lesions; in particular, 22.1% presented an occlusive pattern and 37.1% a proliferative pattern. At follow-up angiographic, restenosis and major adverse cardiac events (MACE) rates were, respectively, 20.8% and 29.6%. The univariate predictors of angiographic restenosis were procedural geographic miss, pattern IV ISR, manual pullback maneuver of the radiation source, preprocedural lesion percentage stenosis and preprocedural lesion MLD. At logistic regression analysis, only geographic miss and pattern IV ISR were independent predictors of post intracoronary radiation therapy (IRT) angiographic restenosis. CONCLUSION: These data indicate that 7-month angiographic restenosis after (32)P IRT in complex patients with ISR is not a frequent event and is predicted mainly by an occlusive lesion at baseline and by procedural geographical miss.

Protection of Mucuna pruriens seeds against Echis carinatus venom is exerted through a multiform glycoprotein whose oligosaccharide chains are functional in this role.

In a previous paper we demonstrated that extracts of Mucuna pruriens seeds (MPE) protect mice against Echis carinatus venom (EV) by an immunological mechanism. In this paper we demonstrate that the MPE immunogen generating the antibody that cross-reacts with the venom proteins is a multiform glycoprotein (gpMuc) whose immunogenic properties mainly reside in its glycan-chains. The glycoprotein was purified from the protein extract of M. pruriens seeds using Concanavalin A affinity chromatography. Using 2-D gel electrophoresis it separated into seven isoforms having MWs in the range from 20.3 to 28.7 kDa and pIs from 4.8 to 6.5. N-terminal sequencing of these spots revealed close similarity since all of them contained the consensus sequence DDREPV-DT found in soybean Kunitz-type trypsin inhibitor. We suggest that gpMuc contains both N- and O-glycans. Mild alkaline treatment but not PNGase F led to loss of reactivity, indicating that O-glycans are probably involved in the antigenicity of gpMuc.

Primary non-Hodgkin's lymphoma of the bone: treatment and analysis of prognostic factors for Stage I and Stage II.

PURPOSE: Primary non-Hodgkin's lymphomas of the bone (PLB) are very rare diseases accounting for 3%-5% of primary bone tumors. The best treatment for PLB has not been found yet. We report on the experience of the Radiation Oncology Department of Bologna University, Italy, relative to the diagnosis and treatment of this disease. METHODS AND MATERIAL: Seventy-seven patients with newly diagnosed PLB were treated from June 1983 to October 2001. Fifty-six were male (72.7%) and 21 were female (27.3%); the median age was 41.8 years, with a range of 16-84 years. The majority of patients had B-cell high-grade histology. The median follow-up was 149 months. Forty-four patients had a solitary bone lesion (Stage I); and in 33 patients, the tumor was spread to locoregional lymphatic area (Stage II). All patients were treated with radiotherapy (RT) with a median dose of 40 Gy (range, 36-54 Gy), and 67 received an additional anthracycline-based regimen of chemotherapy (combined modality therapy [CMT]). RESULTS: After therapy 73 of 77 patients (94.8%) reached a complete remission. At a median time of 23 months, 14 of 77 patients (18.2%) had a disease relapse. Four of them were treated with RT alone (in these cases tumor lesions were <3 cm and located at sites different from mandible); 10 patients were treated with combined RT and CMT. Actuarial disease-free survival (DFS) and overall survival (OS) at 15 years were, respectively, 76.6% and 88.3%. No local failures were seen. Prognostic factors such as age, sex, stage, and bulky lesions were analyzed. Age (<40 vs. >40 years) was the only significant factor for DFS (85.3% vs. 66.6%, p = 0.03). Bulky lesions apparently did not affect OS (90.9% vs. 72.7%). However, the difference has no statistical significance (p = 0.05). Acute and late toxicity related to the treatment was moderate. CONCLUSIONS: In PLB the CMT seems to produce a better outcome than RT alone; that still remains the best treatment for local disease control. Radiation therapy alone should be reserved for mandibular tumors, which are usually very small and earlier diagnosed.

[Intracoronary beta-radiotherapy in high-risk in-stent restenosis. Prospective results of a single center registry]. / Efficacia a lungo termine della brachiterapia endocoronarica beta (32P) nel trattamento delle ristenosi intrastent ad elevato rischio. Risultati prospettici di un registro monocentrico.

BACKGROUND: The aim of the study was to evaluate, on single center prospective data, long-term angiographic and clinical results of intracoronary beta (32P) brachytherapy in "real world" patients with high-risk in-stent restenosis lesions. METHODS: Sixty-nine consecutive patients (77 lesions) with high-risk in-stent restenosis (mean lesion length 30.3 +/- 16.1 mm, pattern III-IV 57.2%, diabetes 33.3%) treated with percutaneous dilation procedures and beta-radiation therapy, underwent 7-month clinical and angiographic follow-up. RESULTS: One patient (1.4%) presented with procedural non-Q wave myocardial infarction. At a mean follow-up of 7 +/- 1.5 months, death was observed in 1 patient (1.4%) and non-Q wave myocardial infarction in 3 (4.3%) (in 2 patients, who prematurely discontinued antiplatelet therapy, caused by late coronary thrombosis). Seven-month binary angiographic restenosis occurred in 20 lesions (25.9%) (in-stent restenosis 11.6%). Target lesion and target vessel revascularization occurred in 20 (28.9%) and 21 (30.4%) patients. At follow-up only 12 (17.3%) patients presented with CCS class III-IV angina. After intracoronary beta brachytherapy angiographic restenosis occurred regardless of the vessel size, lesion length and ostial location. On the contrary a high restenosis rate was documented in obstructive lesions. CONCLUSIONS: As applied in routine clinical practice, radiation therapy is safe and effective in the treatment of high-risk in-stent restenosis. In spite of all that, total occlusion at baseline predicts late angiographic restenosis.

Beta brachytherapy of an old degenerated saphenous vein graft with occlusive in-stent restenosis.

We report a case of obstructive in-stent restenosis in a diffusely diseased saphenous vein graft complicated by a non-ST-elevation myocardial infarction. With tirofiban infusion, the extensively occluded saphenous bypass was reperfused, establishing a TIMI flow 3, and then entirely irradiated with a beta source (32P) without any complication. At 7 months the patient was asymptomatic and the control angiogram did not reveal any restenosis. In conclusion, 32P beta brachytherapy may be extremely effective not only in case of native vessel in-stent restenosis but also in cases of high-risk vein graft in-stent restenosis.

Proteins from Mucuna pruriens and enzymes from Echis carinatus venom: characterization and cross-reactions.

Mucuna pruriens seeds have been widely used against snakebite in traditional medicine. The antivenin property of a water extract of seeds was assessed in vivo in mice. The serum of mice treated with extract was tested for its immunological properties. Two proteins of Echis carinatus venom with apparent molecular masses of 25 and 16 kDa were detected by Western blot analysis carried out using IgG of mice immunized with extract or its partially purified protein fractions. By enzymatic in-gel digestion and electrospray ionization-mass spectrometry/mass spectrometry analysis of immunoreactive venom proteins, phospholipase A(2,) the most toxic enzyme of snake venom, was identified. These results demonstrate that the observed antivenin activity has an immune mechanism. Antibodies of mice treated with non-lethal doses of venom reacted against some proteins of M. pruriens extract. Proteins of E. carinatus venom and M. pruriens extract have at least one epitope in common as confirmed by immunodiffusion assay.