Most of rare disease (RD) patients are assisted in their homes by their family as informal caregivers, causing a substantial burden among family members devoted to care. The role of informal caregivers has been associated with increased levels of stress, poor physical/mental health and impaired HRQOL. The present study assessed the impact on HRQOL and perceived burden of long-term informal caregiving, as well as the inter-relationships of individuals affected by different RD in six European countries, taking advantage of the data provided by the BURQOL-RD project (France, Germany, Italy, Spain, Sweden and UK). Correlation analysis was used to explore the relation between caregiver HRQOL and caregiver burden (Zarit Burden Interview). Multinomial logistic regression models were used to explore the role of explanatory variables on each domain of caregivers HRQOL measured by EQ-5D. Caregivers’ HRQOL is inversely correlated with burden of caring. Mobility dimension of EQ-5D was significantly associated with patients age, time devoted to care by secondary caregivers, patient gender and patient utility index. Patients’ age, burden scores and patient utility index significantly predict the capacity of caregivers to perform activities of daily living. Employed caregivers are less likely of reporting ‘slight problems’ in pain/discomfort dimensions than unemployed caregivers. The EQ-5D instrument is sensitive to measure differences in HRQOL between caregivers with different levels of burden of care.

Background: Type 2 diabetes mellitus (T2DM) is a chronic disease in which health outcomes are related to decision making by patients and health care professionals. Objective: This study aims to assess the effectiveness of internet-based multicomponent interventions to support decision making of all actors involved in the care of patients with T2DM in primary care. Methods: The INDICA study is an open, community-based, multicenter trial with random allocation to usual care or the intervention for patients, the intervention for health care professionals in primary care, or the combined intervention for both. In the intervention for patients, participants received an educational group program and were monitored and supported by logs, a web-based platform, and automated SMS. Those in the intervention for professionals also received an educational program, a decision support tool embedded in the electronic clinical record, and periodic feedback about patients’ results. A total of 2334 people with T2DM, regardless of glycated hemoglobin (HbA1c) levels and without diabetes-related complications, were included. The primary end point was change in HbA1c level. The main analysis was performed using multilevel mixed models. Results: For the overall sample, the intervention for patients attained a significant mean reduction in HbA1c levels of ‒0.27 (95% CI ‒0.45 to ‒0.10) at month 3 and ‒0.26 (95% CI ‒0.44 to ‒0.08) at month 6 compared with usual care, which remained marginally significant at month 12. A clinically relevant reduction in HbA1c level was observed in 35.6% (191/537) of patients in the intervention for patients and 26.0% (152/586) of those in usual care at month 12 (P=.006). In the combined intervention, HbA1c reduction was significant until month 18 (181/557, 32.6% vs 140/586, 23.9%; P=.009). Considering the subgroup of patients uncontrolled at baseline, all interventions produced significant reductions in HbA1c levels across the entire study period: ‒0.49 (95% CI ‒0.70 to ‒0.27) for the intervention for patients, ‒0.35 (95% CI ‒0.59 to ‒0.14) for the intervention for professionals, and ‒0.35 (95% CI ‒0.57 to ‒0.13) for the combined intervention. Differences in HbA1c for the area under the curve considering the entire period were significant for the intervention for patients and the combined intervention compared with usual care (P=.03 for both). Compared with usual care, the intervention for professionals and the combined intervention had significant longer-term reductions in systolic and diastolic blood pressure. Conclusions: In uncontrolled patients, the intervention for patients at baseline provided clinically relevant and significant longer-term reductions of HbA1c levels. The intervention for professionals and combined intervention also improved the cardiovascular risk profile of patients. Trial Registration: ClinicalTrials.gov NCT01657227; https://clinicaltrials.gov/ct2/show/NCT01657227

(1) Background: The continuous improvement in cancer treatment has led to improvement in patients’ survival and a subsequent increase in the number of cancer survivors living with adverse side effects of cancer treatments, sometimes with a high and adverse impact on their health-related quality of life (HRQOL). Side effects of cancer treatments are frequently associated with chronic status of oxidative stress, inflammation, and/or ischemia. The potential for ozone treatment to modulate those processes and improve some of those adverse effects has previously been described. The aim of this study was to evaluate the effect of ozone treatment on the HRQOL and grade of toxicity in symptomatic cancer survivors. (2) Methods: Before and after ozone treatment, we assessed (i) the HRQOL (according to the EQ-5D-5L questionnaire) and (ii) the grade of toxicity (according to the Common Terminology Criteria for Adverse Events of the National Cancer Institute of EEUU (CTCAE v.5.0)) in 26 cancer survivors with chronic side effects of radiotherapy and chemotherapy. (3) Results: There was a significant (p < 0.001) improvement in the EQ-5D-5L index as per the self-reported outcome evaluation of patients’ health status. All the dimensions of the EQ-5D-5L questionnaire (mobility, self-care, activities, pain/discomfort, and anxiety/depression) and the self-evaluation of the health status using the visual analog scale were significantly improved (p < 0.05). The grade of toxicity was also significantly decreased (p < 0.001). (4) Conclusions: In cancer survivors with chronic side effects of cancer treatment, ozone treatment can improve the grade of toxicity and the HRQOL. These results merit additional research. Further studies are ongoing.

Type 2 diabetes mellitus is a chronic disease whose health outcomes are related to patients and healthcare professionals’ decision-making. The Diabetes Intervention study in the Canary Islands (INDICA study) aims to evaluate the effectiveness and cost-effectiveness of educational interventions supported by new technology decision tools for type 2 diabetes patients and primary care professionals in the Canary Islands. The INDICA study is an open, community-based, multicenter, clinical controlled trial with random allocation by clusters to one of three interventions or to usual care. The setting is primary care where physicians and nurses are invited to participate. Patients with diabetes diagnosis, 18–65 years of age, and regular users of mobile phone were randomly selected. Patients with severe comorbidities were excluded. The clusters are primary healthcare practices with enough professionals and available places to provide the intervention. The calculated sample size was 2,300 patients. Patients in group 1 are receiving an educational group program of eight sessions every 3 months led by trained nurses and monitored by means of logs and a web-based platform and tailored semi-automated SMS for continuous support. Primary care professionals in group 2 are receiving a short educational program to update their diabetes knowledge, which includes a decision support tool embedded into the electronic clinical record and a monthly feedback report of patients’ results. Group 3 is receiving a combination of the interventions for patients and professionals. The primary endpoint is the change in HbA1c in 2 years. Secondary endpoints are cardiovascular risk factors, macrovascular and microvascular diabetes complications, quality of life, psychological outcomes, diabetes knowledge, and healthcare utilization. Data is being collected from interviews, questionnaires, clinical examinations, and records. Generalized linear mixed models with repeated time measurements will be used to analyze changes in outcomes. The cost-effectiveness analysis, from the healthcare services perspective, involves direct medical costs per quality-adjusted life year gained and two periods, a ‘within-trial’ period and a lifetime Markov model. Deterministic and probabilistic sensitivity analyses are planned. This ongoing trial aims to set up the implementation of evidence-based programs in the clinical setting for chronic patients. Clinical Trial.gov NCT01657227

Surgery is the treatment of choice for symptomatic disc herniation after conservative management. Several studies have suggested the potential utility of intradiscal ozone infiltration in this pathology. The aim of this trial was to compare intradiscal ozone infiltration vs. oxygen infiltration vs. surgery. This was a randomized, double-blinded, and controlled trial in patients on a waiting list for herniated disc surgery. There were three treatment groups: surgery; intradiscal ozone infiltration (plus foraminal infiltration of ozone, steroids, and anesthetic); intradiscal oxygen infiltration (plus foraminal infiltration of oxygen, steroids, and anesthetic). The requirements for surgery. Five years after the treatment of the last recruited patient (median follow-up: 78 months), the requirement for further surgery was 20 % for patients in the ozone group and 60 % for patients in the oxygen group. 11 % of patients initially treated with surgery also required a second surgery. Compared to the surgery group, the ozone group showed: 1) significantly lower number of inpatient days: median 3 days (interquartile range: 3-3.5 days) vs. 0 days (interquartile range: 0-1.5 days), p = 0.012; 2) significantly lower costs: median EUR 3702 (interquartile range: EUR 3283-7630) vs. EUR 364 (interquartile range: EUR 364-2536), p = 0.029. Our truncated trial showed that intradiscal ozone infiltrations decreased the requirements for conventional surgery, resulting in decreased hospitalization durations and associated costs. These findings and their magnitude are of interest to patients and health services providers. Further validation is ongoing.

Objective: This study assesses the effectiveness of different interventions of knowledge transfer and behaviour modification to improve type 2 diabetes mellitus patients’ (T2DM) reported outcomes measures (PROMs) in the long-term. Design : open, community-based pragmatic, multicentre, controlled trial with random allocation by clusters to usual care (UC) or to one of the three interventions. Participants: A total of 2334 patients with uncomplicated T2DM and 211 healthcare professionals were included of 32 primary care centres. Setting: Primary Care Centers in Canary Islands (Spain). Intervention: The intervention for patients (PTI) included an educational group programme, logs and a web-based platform for monitoring and automated short message service (SMS). The intervention for professionals (PFI) included an educational programme, a decision support tool embedded into the electronic clinical record and periodic feedback about patients’ results. A third group received both PTI and PFI (combined intervention, CBI). Outcome measure: Cognitive-attitudinal, behavioural, affective and health-related quality of life (HQoL) variables. Results: Compared with UC at 24 months, the PTI group significantly improved knowledge (p=0.005), self-empowerment (p=0.002), adherence to dietary recommendations (p<0.001) and distress (p=0.01). The PFI group improved at 24 months in distress (p=0.03) and at 12 months there were improvements in depression (p=0.003), anxiety (p=0.05), HQoL (p=0.005) and self-empowerment (p<0.001). The CBI group improved at 24 months in self-empowerment (p=0.008) and adherence to dietary recommendations (p=0.004) and at 12 months in knowledge (p=0.008), depression (p=0.006), anxiety (p=0.003), distress (p=0.01), HQoL (p<0.001) and neuropathic symptoms (p=0.02). Statistically significant improvements were also observed at 24 months in the proportion of patients who quit smoking for PTI and CBI (41.5% in PTI and 42.3% in CBI vs 21.2% in the UC group). Conclusions: Assessed interventions to improve PROMs in T2DM attain effectiveness for knowledge, self-empowerment, distress, diet adherence and tobacco cessation. PTI produced the most lasting benefits. Trial registration number: ClinicalTrials.gov NCT01657227 (6 August 2012) https://clinicaltrials.gov/ct2/show/NCT01657227 .