Key Factors Impacting a Medical Ventilator Supply Chain During the COVID- 19 Pandemic: Lessons for Pandemic Preparedness.

OBJECTIVES: Future pandemics may cause more severe respiratory illness in younger age groups than COVID-19, requiring many more mechanical ventilators. This publication synthesizes the experiences of diverse contributors to Medtronic's mechanical ventilator supply chain during the pandemic, serving as a record of what worked and what didn't, while identifying key factors affecting production ramp-up in this healthcare crisis. METHOD: In-depth, one-on-one interviews (n = 17) were held with key Medtronic personnel and suppliers. Template analysis was used, and interview content was analyzed for signals, initiatives, actions, and outcomes, as well as influencing forces. RESULTS: Key findings revealed many factors limiting ventilator production ramp-up. Supply chain strengths and weaknesses were identified. Political factors played a role in allocating ventilators and also supported production. Commercial considerations were not priority, but economic awareness was essential to support suppliers. Workers were motivated and flexible. Component shortages, space, production processes, and logistics were challenges. Legally based pressures were reported e.g., import and export restrictions. CONCLUSION: Crisis response alone is not enough; preparation is essential. Coordinated international strategies are more effective than individual country responses. Supply chain resilience based on visibility and flexibility is key. This research can help public health planners and the medical device industry prepare for future healthcare crises.

Reducing Metabolic Dysregulation in Obese Latina and/or Hispanic Breast Cancer Survivors Using Physical Activity (ROSA) Trial: A Study Protocol.

Background: Latina and Hispanic breast cancer survivors (LHBCS) are at increased risk for long-term complications and poorer metabolic health, including metabolic dysregulation (MetD) before and following breast cancer diagnosis. MetD can increase risk of cancer recurrence, death, and comorbid conditions by increasing inflammation and cancer cell proliferation. While exercise improves physical fitness and metabolic outcomes in breast cancer survivors, there is a lack of studies including underrepresented and disadvantaged minority groups such as LHBCS. Methods: Our 12-month randomized (exercise or attention control) controlled trial (the ROSA trial) aims to utilize a progressive combined aerobic and resistance exercise program to improve MetD, insulin resistance, and visceral adiposity among obese LHBCS. We aim to recruit 160 women with Stage I-III breast cancer who are sedentary, centrally obese, and have completed treatment (e.g., surgery, radiation, chemotherapy) prior to enrollment. Participants randomized to the exercise group receive 16-weeks of virtually supervised aerobic and resistance training, followed by 16-weeks of unsupervised home-based aerobic and resistance exercise, and 16-weeks of follow-up. The attention control group receive a 12-month home-based stretching program. Primary and secondary outcomes are measured every 4-weeks during study visits. Discussion: The ROSA trial is the first exercise oncology trial targeting high-risk sedentary, obese LHBCS to improve MetD-related outcomes. Results of this trial will help illuminate how exercise impacts health-related outcomes, survivorship, and recurrence, and inform future exercise oncology guidelines to reduce health disparities among minority cancer survivors.

Implementation of biopsychosocial supported self-management for chronic primary oro-facial pain including temporomandibular disorders: A theory, person and evidence-based approach.

BACKGROUND: Aims of the study were to: Implement supported self-management for chronic primary oro-facial pain in a clinical setting. Evaluate its impact on consultation rates, pain severity, interference with life and patient experience. METHODS: Sixty-six patients with chronic primary oro-facial pain received the intervention at a facial pain clinic at Leeds Dental Institute, UK. Brief Pain Inventory (BPI) scores measured pain severity and interference with life before and after the intervention. Process mining outlined patient care pathways. Monthly consultation rates measured 12 months before and after the intervention were used to evaluate burden on healthcare services and economic impact. Patient feedback was assessed via Patient and Public involvement discussion groups. RESULTS: Mean BPI scores significantly improved after intervention-from 5.70 (SD 1.89) to 3.78 (SD 2.34) (p < .001); mean pain interference score reduced from 19.95 (SD 9.41) to 12.05 (SD 9.64) (p < .001). Average monthly consultations significantly (p = .001) reduced from 0.42/month before the intervention to 0.16/month after the intervention. Economic assessment showed cost savings of £293 per patient per year. Process mining showed high rates of service usage with 31 patients also attending 51 other specialist services between them. Patient and Public Involvement discussion groups with 5 patients identified that the intervention was a 'constant companion' and should be implemented at the outset in the care pathway. CONCLUSION: Supported self-management for chronic primary oro-facial pain has a positive impact on health outcomes (physical functioning, pain intensity and patient experience), as well as service usage and healthcare costs when implemented in a secondary care clinical setting. Reconfiguring current care pathways to upscale early implementation of such interventions should be a priority for future testing.

Aerobic and resistance exercise improve patient-reported sleep quality and is associated with cardiometabolic biomarkers in Hispanic and non-Hispanic breast cancer survivors who are overweight or obese: results from a secondary analysis.

STUDY OBJECTIVES: Poor sleep quality affects nearly one-third of breast cancer survivors and is associated with insulin resistance. The purpose of this secondary analysis was to examine the effects of a 16-week exercise intervention on patient-reported sleep quality among breast cancer survivors and assess whether changes in patient-reported sleep quality were associated with cardiometabolic biomarkers. We explored Hispanic ethnicity as a moderator of the effects of exercise on patient-reported sleep quality. METHODS: Breast cancer survivors who were overweight or obese were randomized to exercise (n = 50) or usual care (n = 50). The 16-week intervention included aerobic and resistance exercise. Patient-reported sleep quality (Pittsburgh Sleep Quality Index [PSQI]) and biomarkers of cardiometabolic health were assessed at baseline and post-intervention. Within- and between-group differences were assessed using general linear models repeated-measures analyses of variance and mixed-model repeated-measure analysis, respectively. Associations between changes in PSQI and cardiometabolic biomarkers were computed using Pearson correlations. Linear mixed-models were used to evaluate effect modification by ethnicity. RESULTS: Participants were 52 ± 10.4 years old, and over half were of Hispanic ethnicity. As compared to usual care, PSQI global scores improved significantly in the exercise group (mean between-group difference -2.2; 95% CI -3.2 to -0.6). Change in PSQI was inversely associated with changes in all cardiometabolic biomarkers (p < 0.01) among the exercise group. Ethnicity was found to moderate the effects of exercise training on global sleep quality (p < 0.001). CONCLUSIONS: An aerobic and resistance exercise intervention effectively improved patient-reported sleep quality in breast cancer survivors. Hispanic ethnicity as a moderator showed greater improvement in patient-reported sleep indicating Hispanic versus non-Hispanic breast cancer survivors may derive larger sleep benefits. CLINICAL TRAIL INFORMATION: NCT01140282.

Hispanic ethnicity as a moderator of the effects of aerobic and resistance exercise on physical fitness and quality-of-life in breast cancer survivors.

BACKGROUND: Exercise can profoundly affect physical fitness and quality of life in breast cancer survivors; however, few studies have focused on minorities. This secondary analysis examines Hispanic ethnicity as a moderator of the effects of a 16-week aerobic and resistance exercise intervention on physical fitness and quality of life in breast cancer survivors. METHODS: Eligible breast cancer survivors (n = 100) were randomized to exercise (n = 50) or usual care (n = 50). The exercise intervention consisted of supervised moderate-vigorous aerobic and resistance exercise thrice weekly for 16 weeks. Physical fitness and quality of life were measured at baseline, post-intervention, and 28-week follow-up (exercise only). Linear mixed-models adjusted for baseline value of the outcome, age, disease stage, adjuvant treatment, and recent physical activity were used to evaluate effect modification by ethnicity. RESULTS: The study sample included 57% Hispanic and 43% non-Hispanic breast cancer survivors. Hispanic breast cancer survivors were younger, less fit, and diagnosed with more advanced cancers compared with non-Hispanic breast cancer survivors (p < 0.001). Ethnicity was found to moderate the effects of exercise training on all physical fitness and quality-of-life measures including VO2max (8.4 mL/kg/min; 95% confidence interval (95% CI) 3.2 to 13.4), physical well-being (12.3; 95% CI 4.2 to 18.4), and emotional well-being (11.4; 95% CI 5.9 to 15.5). In all cases, Hispanics experienced larger benefits than non-Hispanics. CONCLUSIONS: Hispanic breast cancer survivors have poorer cardiorespiratory fitness, muscle strength, and quality-of-life and therefore may derive larger benefits from exercise than non-Hispanic breast cancer survivors. Clinical exercise interventions may attenuate existing health disparities among minority breast cancer survivors. IMPLICATION OF CANCER SURVIVORS: Here we report psychosocial and fitness-related disparities among Hispanic breast cancer survivors when compared with their non-Hispanic counterparts. Our exercise intervention highlights the importance of exercise for minority cancer survivors and the need for distinct, culturally tailored exercise intervention approaches to reduce psychosocial and fitness-related disparities among this understudied population of cancer survivors.

Serum hepcidin measured with an improved ELISA correlates with parameters of iron metabolism in patients with myelodysplastic syndrome.

Patients with myelodysplastic syndromes (MDS) often show elevated serum ferritin levels at diagnosis, probably caused by increased intestinal iron uptake attributable to ineffective erythropoiesis. Many patients also develop transfusional iron overload. Hepcidin, a pivotal regulator of iron homeostasis, controls iron uptake in the duodenum as well as iron release from macrophages and is potentially involved in iron distribution to different organs. We measured serum hepcidin, together with other laboratory parameters related to iron metabolism and hematopoiesis (ferritin, transferrin, transferrin saturation, soluble transferrin receptor, erythropoietin, and hemoglobin), and C-reactive protein as marker of inflammation, in 89 MDS patients. Hepcidin levels were measured with two different competitive ELISAs: (a) EIA-4705 as described by Schwarz et al. (J Gastroenterol 46:648-656; 2011) and (b) Hepcidin 25 bioactive ELISA (EIA-5258), which was develop by DRG Diagnostics, Marburg, in 2012. Median hepcidin levels with EIA-5258 were as follows: entire cohort 17.5 ng/ml (n = 89), RA/RARS 5.9 ng/ml (n = 5), RCMD 17.8 ng/ml (n = 38), RS-RCMD 8.7 ng/ml (n = 7), RAEB I/II 29.1 ng/ml (n = 22), CMML I/II 16.9 ng/ml (n = 10), and MDS with del(5q) 26.3 ng/ml (n = 7). Hepcidin levels of the RA/RARS patients were significantly lower than in the other groups except RS-RCMD. RS-RCMD had significantly lower levels than RAEB and 5q- patients. There was a positive correlation between hepcidin levels and serum ferritin and transferrin saturation, and a negative correlation between hepcidin and hemoglobin and transferrin. Malcovati et al. (Blood 112:2676a, 2008), Santini et al. (PLoS One 6:e23109, 2011), and Ambaglio et al. (Haematologica 98:420-423, 2013), using mass spectrometry, reported similar results. We further assessed transfusional status and could show that patients who had been transfused have significantly higher hepcidin levels (median 33.3 versus 8.8 ng/ml (p < 0.001)). A dichotomized hepcidin level correlated with worse survival. EIA-4705 as described by Schwarz showed no correlation with markers of iron metabolism. Measurement of serum hepcidin with an improved ELISA yield results that correlate with other parameters of iron metabolism as well as survival and transfusion needs.

Improved survival in MDS patients receiving iron chelation therapy - a matched pair analysis of 188 patients from the Düsseldorf MDS registry.

MDS patients are prone to develop transfusional iron overload. Iron overload may partly explain why transfusion dependency is associated with a decreased likelihood of survival. Our matched-pair analysis included 94 patients on long-term chelation therapy and 94 matched patients without it. All patients had iron overload, defined as serum ferritin (SF) above 1000 ng/ml or a history of multiple transfusions and SF ≥ 500 ng/ml. Median SF was 1954 ng/ml in chelated and 875 ng/ml in non-chelated patients. The difference in median survival (74 vs. 49 months, respectively; p=0.002) supports the idea that iron chelation therapy is beneficial for MDS patients.

Results of a phase 2 study of valproic acid alone or in combination with all-trans retinoic acid in 75 patients with myelodysplastic syndrome and relapsed or refractory acute myeloid leukemia.

Valproic acid (VPA) inhibits histone deacetylase activity and induces differentiation of acute myeloid leukemia (AML) blasts in vitro. We observed clinical responses to VPA in patients with myelodysplastic syndrome (MDS) and AML. Here, we report follow-up data on 75 patients. Of these, 66 were started on VPA monotherapy, with later addition of all-trans retinoic acid (ATRA) in patients who did not respond or relapsed. Nine patients were treated with VPA + ATRA from the start. Median treatment duration was 4 months for VPA and 2 months for ATRA. Hematological improvement, according to international working group criteria for MDS, was observed in 18 patients (24%). Median response duration was 4 months. ATRA exerted no additional effect in patients receiving the combination from the start or benefited primary VPA nonresponders. However, of ten VPA responders who relapsed, four achieved a second response after addition of ATRA. Response rates were strongly dependent on disease type according to WHO classification. We found a response rate of 52% in MDS patients with a normal blast count (refractory sideroblastic anemia, refractory cytopenia with multilineage dysplasia, and refractory sideroblastic cytopenia with multilineage dysplasia). The response rate was 6% in refractory anemia with excess blasts (I + II), 16% in AML, and 0% in chronic myelomonocytic leukemia. Bone marrow blast count was the only variable that predicted responses. We conclude that VPA is clinically useful in low-risk MDS. For patients with high-risk MDS, VPA may be combined with chemotherapy or demethylating drugs. If patients relapse after an initial response to VPA, ATRA has the potential to induce a prolonged second response.

Monitoring of bone formation during distraction osteogenesis via osteocalcin: a time sequence study in dogs.

The aim of the current study was to analyze the osteocalcin level and radiographic density during distraction osteogenesis in order to investigate the role of osteocalcin in monitoring bone formation during callus distraction. Lengthening of the right tibia by 25% was performed in 12 beagle dogs by callus distraction after osteotomy and application of a ring fixator. Distraction was started on the 5th postoperative day, with a distraction rate of 0.5 mm twice a day, and was ended after 25 days. Blood samples and x-rays of the callus distraction segment were obtained preoperatively and once a week until day 55 after operation. A digital radiograph analysis system was used to determine the bone density of the callus distraction segments. The serum parameters of osteocalcin were evaluated by radioimmunoassay. The radiographic bone densities during the distraction phase increased during the distraction period and markedly increased during the consolidation period. A similar trend was observed for osteocalcin, whereby the coefficient of correlation between these two parameters was, on average, 0.68 +/- 0.11. However, the radiographic bone density measurements, as well as the osteocalcin levels, showed large variation between different animals. Therefore, our results suggest that valuable information about bone formation during distraction osteogenesis can be obtained via serum osteocalcin levels, even though it seems that time sequence monitoring is more favorable than the determination of absolute values.