Aromatherapy is the field of herbal medicine that uses essential oils distilled from flowers, roots, and herbs and other plant compounds to promote physical and psychological well-being. Essential oils are absorbed into the body in different ways, with the inhaled and topical routes being the most widely used. The aim of this review was to critically evaluate and synthesize the available scientific evidence on the efficacy and safety of aromatherapy for the management of any therapeutic indication. This report was requested by the Spanish Ministries of Health and Science and Innovation.

An overview of systematic reviews (SRs) was performed. The MEDLINE, Embase, CINAHL, and PsycINFO databases were searched for literature published from January 2006 to August 2021. SRs reporting the efficacy and safety of aromatherapy were included. We applied no restrictions in terms of administration route or essential oil used. Two reviewers independently performed screening and selection, data extraction, and quality assessment.

We included 74 SRs covering a wide variety of populations and settings. The most reported outcome was anxiety, followed by pain, and the most commonly used essential oil was lavender. Fifteen SRs reported mild adverse events with aromatherapy. Only 11 SRs assessed the certainty of evidence using the GRADE approach. Aromatherapy reduced heart rate and likely reduces anxiety and breathing rate in patients with cardiovascular diseases. Aromatherapy probably also reduces pain in women with primary dysmenorrhea. Additionally, it may reduce blood pressure, acute pain, subjective stress, and the need for antiemetic drugs after surgical procedures. However, the evidence was very uncertain regarding the effect of essential oils on anxiety, pain, and quality of life in patients with cancer, anxiety and pain after a caesarean section, and dental anxiety.

Aromatherapy may be useful for managing psychological and physical symptoms in different settings. However, the conclusions of this review are not definitive because of the moderate to high risk of bias in many of the primary studies included in the SRs.

FreeStyle Libre System (FSL) is a minimally invasive technology, which provides frequent information about interstitial glucose levels, which allows adjustment of insulin dose and a reduction in the number of fingersticks. This study aims to evaluate the effectiveness and safety of FSL in childhood and adolescence.

Prospective case series in 27 Spanish hospitals. Patients aged 4-17 years with type 1 diabetes mellitus (T1DM) were included. Follow-up was done at 3, 6 and 12 months after starting to use the FSL. Outcome measures were HbA1c levels, acute complications of DM (severe hypoglycemia, ketoacidosis), DM knowledge, health-related quality of life, satisfaction and adverse effects. Biochemical glycemic outcomes (e.g., glycemic variability, time in therapeutic range) were available from 3 to 12 months. Mixed regression models with repeated time measurements were implemented.

The mean age of patients was 12.6 years, with 56.4 percent had HbA1c values above 7.5 percent at baseline. This subgroup significantly improved their HbA1c levels at 3, 6 and 12 months (-0.46%, -0.44% and -0.35%, respectively). Patients with controlled HbA1c levels significantly worsened at 12 months (0.29%). There was a significant reduction in severe hypoglycemic episodes, but only in the multiple imputation analysis. In patients controlled at baseline, there were significant reductions between 3 and 12 months in the percentage of time under 55mg/dl (-0.64%), above 250mg/dl (-1.8%) and glycemic variability (-2.6%). In uncontrolled patients, there was a significant reduction in time above 250mg/dl (-5.8%) between 3 and 12 months follow-up. There was no significant improvement in knowledge about disease, although general self-perceived health worsened and general satisfaction improved. Mild adverse events such as skin reactions (14%) and discomfort or pain (11.3%) with no significant reductions in follow-up were recorded.

The use of FSL in childhood and adolescence with T1DM produces a significant reduction in HbA1c levels in patients with uncontrolled HbA1c levels along with a reduction in severe hypoglycemic episodes (in the multiple imputation analysis). FSL-related adverse effects are considered mild.

GesPeDia is a web-based application that provides aggregate clinical information, using outcome and process indicators, and disaggregated patient information. Information is obtained from the electronic medical records. GesPeDia aims to promote people-centered care, improve monitoring of patients’ health outcomes and quality of professional performance. This study aims to evaluate usability, acceptability and satisfaction of GesPeDia.

Nineteen evaluators were included (2 management technicians, 9 health center directors and 8 endocrine consultants). They had access to GesPeDia for two months. Perception of their usefulness for decision-making, acceptability and design satisfaction were measured with an online questionnaire. In addition, suggestions for improvements in the app’s functionalities were collected. Finally, a sample of the evaluators were included in a semi-structured interview to deepen the analysis of dimensions. A descriptive analysis of the data was performed.

The questionnaire was completed by 10 professionals, with mean age of 51.1 years and professional experience 16.5 years. Among the evaluators, 60 percent considered the app quite useful and only 10 percent found it inappropriate for their daily activities. Each of the indicator blocks was rated quite useful. Eight percent considered GesPeDia moderately fast, although for 20 percent navigation within the app was not very intuitive. Appearance was positively valued by 80 percent, despite the fact that 30 percent considered that design does not favor the understanding of contents. Seventy percent considered degree of reliability, relevance and clarity of the contents to be high. Most indicated that information provided by GesPedia is complete for decision-making.

GesPeDia is valued positively by evaluators as a decision-making tool.

Diabetes mellitus (DM) is one of the most frequent metabolic complications associated with pregnancy, affecting both the prognosis of the pregnant woman and the newborn. Pregestational DM type 1 (T1DM) and type 2 (T2DM) and gestational DM (GDM) are associated with an increased risk of pregnancy complications such as miscarriage, fetal malformations, macrosomia, preeclampsia, and neonatal hypoglycemia, among others. The aim of this review was to evaluate the efficacy and safety of using the Dexcom G6 device (Dexcom, Co., USA) to continuously self-monitor blood glucose levels during pregnancy. This report was requested by the Spanish Ministry of Health.

We systematically searched for articles published to July 2021 in the MEDLINE, Embase, and Web of Science databases. We included experimental and observational primary studies addressing the safety, efficacy, and cost effectiveness of the Dexcom G6 device for gestational and pregestational diabetes.

Two non-comparative prospective studies were identified. One study of 25 pregnant women with T1DM, which evaluated glycemic control and complications during pregnancy and postpartum, reported stable hemoglobin A1c levels during gestation in women using the Dexcom G6 device. The percentage of time spent in the therapeutic glucose range (63 to 140 mg/dL) was 59 percent; 38 percent was in the hyperglycemic range and 3 percent was in the hypoglycemic range. Although some patients reported mild erythematous and edematous reactions to the sensor, no moderate or severe reactions or infections occurred at the sensor insertion site. The other study in pregnant women with T1DM (n=20), T2DM (n=3), or GDM (n=9) showed adequate accuracy of the Dexcom G6 device, compared with the reference method, especially when the sensor is placed on the arm.

Randomized controlled trials are required to assess the effectiveness and safety of the Dexcom G6 device in maintaining adequate glucose control during pregnancy in women with DM. Studies are also needed to compare the Dexcom G6 device with conventional capillary blood glucose self-monitoring or other monitoring methods. No cost-effectiveness studies have been conducted for the Dexcom G6 device in this patient population.

Chemotherapy-induced alopecia (CIA), although reversible, is one of the most common and distressing side effects of cancer therapy, affecting approximately 65 percent of all patients and influencing treatment decisions in some of them. Scalp cooling (SC) is a method aiming to prevent CIA. Our study aims to evaluate the real value of SC devices.

A systematic review of the available scientific literature on the safety, effectiveness and cost-effectiveness of the use of SC compared with no intervention was performed. Overall effect size was estimated through a meta-analysis. An economic analysis in the Spanish context from the Spanish National Healthcare System (NHS) and social perspectives was performed.

Thirteen randomized controlled trials (n = 832) were included but only nine contributed to the meta-analysis. A large effect in favor of SC reducing hair loss was found (RR=0.57; 95% CI: 0.46-0.69). No differences were observed according to the type of cancer, although there was a small positive effect for breast cancer. A higher effect was found in patients treated with a combination anthracyclines/taxanes treatment compared to those treated only with anthracyclines. The only economic evaluation found in the literature was conducted in The Netherlands and concluded that Paxman system was less costly than usual care from societal perspective and no differences in quality adjusted life years (QALYs) were observed. The de novo economic analysis showed that the strategies including SC devices generated more costs and QALYs (given some assumed utility values) than usual care (not SC), presenting incremental cost-effectiveness ratios below the threshold calculated for Spain (EUR 25,000 /QALY), from both perspectives.

The results suggest that SC are effective for the prevention of CIA. Furthermore, assuming the utility values used in the model, SC devices are cost-effective compared to usual care (not SC).

It is estimated that approximately 1.1 million cases of prostate cancer (PCa) are diagnosed in the world every year. In general, PCa is a slow-onset cancer and less than 10 percent of cases are detected in the metastatic phase. In order to identify patients at risk of suffering from clinically significant prostate cancer (csPCa), as well as to avoid unnecessary biopsies, overdiagnosis and overtreatment, a variety of molecular biomarker detection tests have been developed.

We undertook a systematic review with meta-analyses on the effectiveness of diagnostic tests based on biomarkers in blood or urine samples for the identification of men at risk of csPCa. A cost-effectiveness analysis was conducted using a decision tree model for the short term and a Markov model for the long term, both from the social and the National Health System perspectives. The effectiveness measure was quality-adjusted life years (QALYs). We ran extensive sensitivity analyses, including a probabilistic sensitivity analysis.

Sixty-five studies were included with a total of 34,287 participants. The diagnostic tests analyzed were: PHI, Progensa® PCA3, SelectMDx, MyProstateScore, 4Kscore®, TMPRSS2: ERG, Stockholm3, ExoDx Prostate IntelliScore and Proclarix®. All studies included biopsy as comparator. The sensitivity and specificity of diagnostic tests depended on the test itself and the threshold chosen, and ranged from 42 percent to 99 percent and from 13 percent to 87 percent, respectively. In the cost-effectiveness analysis, the alternative that includes the biomarker, specifically the SelectMDx, led to higher QALYs and healthcare costs with an estimated incremental cost-effectiveness ratio (ICER) of 6,640.21 EUR per QALY. The sensitivity analyses confirmed that the results were robust.

Biomarker testing to select men at risk of csPCa who should undergo prostate biopsy can be a cost-effective strategy depending on its cost per determination and its sensitivity/specificity. The analyses carried out indicate that the SelectMDx biomarker is cost-effective at a cost of EUR 375 per determination.

Telemedicine strategies have been broadly introducing in health services during the COVID-19 pandemic, including in care of neurological diseases.

A rapid realist review was conducted using EUnetHTAs Core Model 3.0 and GRADE evidence to decision frameworks were used as frameworks to describe the ethical, legal, organizational, social and patient aspects (ELSI+) related to the use of teleneurology (TN) A scoping multistakeholder meeting helped defined the scope and research questions of the assessment. Patient representatives, clinicians, scientific society representatives with relevant experience in TN were invited and participated. Industry representatives were also present. Systematic searches for ethical, legal, organizational, social and patients related aspects were conducted. Additional manual searches contributed to contextualize these dimensions in the Spanish context. A narrative synthesis was undertaken.

Main results of the assessment of the ELSI+ aspects of TN were described. TN applications are diverse depending on the condition, objective of care and technology used. The implementation of TN lacks specific legal frameworks which implies legal uncertainty. TN may increase geographical accessibility to neurological care in remote areas and by reducing difficult commuting to specialized care centers. Nevertheless, accessibility is challenged by reduced access to technology, the digital divide, lack of health literacy or technologies not adapted to functional diversity. Therefore, equity is not guaranteed if it is offered as a non-voluntary basis or with no support. TN tends to be accepted by patients and carers if it has enough quality, saves travelling time and costs and does not dehumanize care as it is perceived as more flexible and convenient. Quality of TN needs an interdisciplinary team with skills to coordinate organizational aspects of the implementation which include among others, the planification of the support to patients and carers before, during and after the consultation. Health professionals may also need to learn adapted communicational and technological skills.

The implementation of TN poses many ethical, legal, organizational, social or patient-centered challenges.

Autogenic training consists of reaching a state of deep relaxation through mental representations of physical sensations in different parts of the body. It is a promising technique for improving the psychological well-being of people with chronic diseases, but there are no clinical practice guidelines recommending the use of autogenic training in this population. The aim of this work was to identify, critically evaluate, and synthesize the available evidence on the safety and effectiveness of autogenic training in the prevention and treatment of medical conditions.

We conducted a systematic search for systematic reviews and randomized controlled trials (RCTs) in MEDLINE, Embase, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials. The selection and assessment of risk of bias of the included studies was carried out independently by two reviewers.

A total of 2,420 references were identified after eliminating duplicates. Of these, 141 were selected for reading the full text, and 13 systematic reviews and 18 RCTs were included. Compared with no intervention or delayed treatment, autogenic training significantly reduced levels of anxiety and depression as well as some physical symptoms (e.g., headaches and atopic dermatitis).

Autogenic training could be useful for improving the psychological well-being and physical symptoms of patients with chronic health conditions and as an additional element in multicomponent intervention programs. However, these conclusions are not definitive due to the low number of studies available for each health condition and their high or unclear risk of bias.

Foot reflexology is a type of complementary manual therapy that consists of applying pressure or massage to the sole of the foot to produce various therapeutic effects in other body areas or organs. This technique has been used in many different clinical indications, but there is uncertainty about its real effect. A health technology assessment (HTA) was conducted to analyze the efficacy and safety of foot reflexology within the framework of the “Health Protection Plan Against Pseudo-Therapies,” which was established in 2018 by the Spanish Ministry of Health and the Ministry of Science and Innovation.

A systematic review and metanalysis was conducted to synthesize the available scientific literature on the efficacy and safety of foot reflexology in people of any age with any disease or medical condition.

Sixty-eight randomized controlled studies were included. Pooled estimates indicated that foot reflexology had no effect on pain, fatigue, depression, quality of life, quality of sleep, or blood pressure, compared with non-reflexological foot massage. Improvements in pain (standardized mean difference [SMD] −1.11, 95% CI: −1.70 - −0.52), fatigue (SMD −0.93, 95% CI: −1.36 - −0.51), sleep quality (SMD −1.11, 95% CI: −1.68 - −0.34), and systolic (mean difference [MD] −7.36, 95% CI: −8.49 - −6.23) and diastolic (MD −5.07, 95% CI: −0.98 - −0.22) blood pressure were obtained when reflexology was compared with usual care or no intervention. In the case of anxiety levels, the benefit obtained with foot reflexology compared with any comparator (SMD −0.6, 95% CI: −0.98 - −0.22) was attenuated when compared with non-reflexological foot massage (SMD −0.2, 95% CI: −0.36 - −0.03). Very few studies reported on the safety of foot reflexology.

There was no evidence for any specific effect of reflexology for any condition when compared with non-reflexological foot massage, except for a positive effect on anxiety levels.

The PapSEEK test is an emerging minimally invasive technique in which samples are collected from the endocervical or intrauterine cavity with the Papanicolaou (Pap) brush or the Tao brush to detect somatic mutations or aneuploidies indicating the presence of endometrial or ovarian cancer.

We systematically searched for articles published up to October 2020 in the following electronic databases: Medline, Embase, the Cochrane Library, and the Centre for Reviews and Dissemination. We included experimental studies, observational primary studies, and cost-effectiveness studies evaluating the safety, effectiveness, and cost effectiveness of the PapSEEK test for the early detection of ovarian or endometrial cancer. Relevant outcomes included sensitivity, specificity, the coefficient of variation, re-test rates, the incremental cost-effectiveness ratio, the incremental cost-utility ratio, and the cost of each alternative.

A single relevant retrospective study was identified. In this study, samples from women with endometrial cancer (n = 656) and ovarian cancer (n = 254) were collected with the Pap brush and Tao brush and compared with samples from healthy women (n = 1,002). The diagnostic validity for somatic mutation or aneuploidies obtained with a Pap brush had a sensitivity of 81% for endometrial cancer and 33% for ovarian cancer, and a specificity of 99% for both conditions. When samples were collected from the intrauterine cavity with a Tao brush, the sensitivity increased to 93% for endometrial cancer and to 45% for ovarian cancer. The sensitivity of the PapSEEK test increased only for ovarian cancer when plasma samples to detect circulating tumor DNA were collected in addition to Pap smear samples. This strategy provided a diagnostic validity of 43%, which was higher in late-stage ovarian cancer (56% versus 35%), and a specificity of 100%.

Prospectively designed studies are required to assess the safety and effectiveness of the PapSEEK test in screening settings, as well as studies comparing the technology with conventional screening methods. No cost-effectiveness studies have been conducted for the PapSEEK test.

Hepatitis A (HA) is a liver disease with a low mortality rate, but it can cause debilitating symptoms and fulminant hepatitis in some cases. Its incidence is greater in geographical areas with poor sanitation and hygiene. Spain is considered a low-endemicity country, so universal childhood immunization against HA is currently not financed by the National Health System. The aim of this study was to synthesize the scientific evidence on the cost effectiveness of universal childhood vaccination against HA.

Full economic evaluations, published in the English or Spanish languages, were included if they reported outcome measures related to the prevention of HA, adverse effects, or incremental cost-effectiveness ratios (ICERs). The Medline, Embase and Cochrane Library databases were searched for articles published from the beginning of the databases to April 2018.

A total of 23 economic evaluations were included: one in a country of high endemicity, nine in countries of intermediate endemicity, and 13 in countries with low endemicity. Only one Spanish study, published in 1997, was found. Studies conducted in high- and intermediate- endemicity countries concluded that a universal childhood vaccination program against HA was a cost-effective option. However, in the case of countries with low endemicity the results were heterogeneous, although most agreed that a systematic vaccination strategy would not be a cost-effective option and that the adoption of such a strategy would not be justified given the limited benefits it would offer. The results of the economic evaluations depended on parameters such as the price and duration of the vaccine effect and the program coverage.

In countries with low endemicity the results were heterogeneous, although most studies concluded that the implementation of a universal vaccination strategy is not justified from the point of view of cost effectiveness.

About 70 percent of metastatic breast, lung, and prostate cancers affect the bones. When this phase of the disease affects the spine, the mobility and quality of life of patients are severely impaired. Radiofrequency ablation (RFA) has become a feasible option in the palliative treatment of vertebral metastases due to its minimal invasiveness and short procedure time. This health technology assessment report aimed to identify, evaluate, and synthesize evidence on the safety, effectiveness, and cost effectiveness of RFA for vertebral metastases.

A systematic search was conducted to identify literature published from December 2016 to July 2019 in the following databases: Medline, Embase, the Cochrane Library, and the Centre for Reviews and Dissemination. Systematic reviews, randomized and non-randomized controlled trials, and case series studies evaluating the efficacy and safety of RFA in patients with vertebral metastases were included.

Sixteen studies were included: two systematic reviews, 13 case series studies, and one comparative study. None of the systematic reviews identified any randomized controlled trials. Of the 14 included primary studies, 10 evaluated RFA in combination with vertebroplasty, three evaluated RFA in combination with kyphoplasty, and one study evaluated a combination of RFA and radiation therapy. In all cases, the evaluated patients had different types of cancer (e.g., breast, lung, or liver). The follow-up periods varied between the studies from one day to 12 months. The most commonly used RFA devices were the STAR™ Tumour Ablation System (Merit Medical Systems) and the OsteoCool™ Radiofrequency Ablation System (Medtronic).

RFA reduces pain, improves functional capacity, and provides greater local control of disease, potentially giving patients a higher quality of life, even in the context of metastatic disease. Although there is evidence on the safety and efficacy of this technology for the palliative treatment of vertebral metastases, more studies with higher methodological quality are needed. There were no studies available on the cost effectiveness of RFA for this indication.

This paper aims to describe the development of a flowchart to guide the decisions of researchers in the Spanish Network for Health Technology Assessment of the National Health System (RedETS) regarding patient involvement (PI) in Health Technology Assessment (HTA). By doing so, it reflects on current methodological challenges in PI in the HTA field: how best to combine PI methods and what is the role of patient-based evidence.

A decisional flowchart for PI in HTA was developed between March and April 2019 following an iterative process, reviewed by the members of the PI Interest Group and other RedETS members and validated during an online deliberative meeting. The development of the flowchart was based on a previous methodological framework assessed in a pilot study.

The guidelines on how to involve patients in HTA in the RedETS were graphically represented in a flowchart. PI must be included in all HTA reports, except those that assess technologies with no relevant impact on patients’ experiences, values, and preferences. Patient organizations or expert patients related to the topic of the HTA report must be identified and invited. These patients can participate in protocol development, outcomes' identification, assessment process, and report review. When the technology assessed affects in a relevant way patient experiences, values, and preferences, patient-based evidence should be included through a systematic literature review or a primary study.

The decisional flowchart for PI in HTA contributes to the current methodological challenges by proposing a combination of direct involvement and patient-based evidence.

Conclusions and recommendations of health technology assessment (HTA) reports have an impact on all relevant actors involved in the health system (health authorities, administrators, health professionals, patients, citizens and industry). The involvement of all those relevant stakeholders in the HTA process facilitates making valid and informed decisions and an efficient allocation of resources. Improving communication, participation and transparency among all agents will lead to more efficient evaluation and decision-making processes.

To review key aspects of the relations between HTA agencies and health industries, two process were carried out: a narrative review of literature searched in Medline, PubMed, Embase, CINAHL and WOS (2007-2017) and a review of websites of international HTA agencies. References and webs with information on the framework, objectives, methodologies, impact or results of the relationships were included.

A total of 1961 references were located and forty-five were selected. From the synthesis of the selected references the following key aspects of the relationships between HTA and industry were identified: (i) the importance of early dialogues with industry to align HTA objectives with the generation of evidence; (ii) challenges of the bias in the evidence produced by industry; (iii) difficulties in industry engagement in HTA processes; and (iv) industry interest in HTA. The review of six agency websites provided information on industry involvement in strategic activities, early dialogues, provision of documentation, management of industry clarifications, review of the report/allegations and other forms of relationship.

Both the review of the literature and the contents of the web pages of international agencies with experience in relations with industry show that the interest is in the creation of collaborative frameworks between regulatory authorities that decide on authorization and price and reimbursement and HTA agencies, while both try to maintain an early, transparent and systematic interaction with the healthcare industry.

The aim of this study was to develop a feasible and effective strategy to involve patients in the Spanish Network of Agencies of Health Technology Assessment (RedETS).

The framework for patient involvement (PI) in the assessment activities and processes of RedETS were developed through a research project that included: (i) a systematic search of the international literature describing a strategy and/or a methodology linking health technology assessment (HTA) and PI; (ii) a qualitative study through interviews with RedETS members to analyze the perceptions of PI among HTA managers in the Spanish context; (iii) a Delphi consultation with three large platforms of patients, carers and consumer organizations in Spain about their perspectives of PI; (iv) a consensus process with the members of the RedETS Governing Council to define the final strategy.

Three main themes were identified in the literature and Web site review: (i) PI methods for the different HTA phases; (ii) Participant definition and selection; (iii) Resources needed. A three-step implementation strategy was proposed: (i) short-term actions: piloting and testing patient participation in HTA and building patients' capacity; (ii) medium-term actions: broadening the participation of patients, and building internal capacity; (iii) long-term actions: consolidating and mainstreaming patient involvement

Patient participation can be incorporated into almost all the HTA phases and products with greater or lesser degrees of difficulty. However, a progressive implementation strategy is suggested for a feasible PI process.

The Spanish National Network (REDETS) is a group of eight agencies, units and services, depending on National and Regional Governments that coordinate their work within a common methodological framework, guided by the principles of mutual recognition and cooperation. The necessity of considering a Quality Management System has been detected and, consequently, a common tool for all the members needs to be developed. We describe in this study the process to achieve that goal.

Based on both a review of previous literature and the proposal for a self-evaluating tool, a group of experts from each agency through consensus have developed a tool for self-evaluation in Health Technology Assessment (HTA) agencies. Through the structure described in the handbook of the Andalusian Agency for Healthcare Quality (ACSA), each standard should have a statement or proposal that needs to also include evidence or good practices, and the corresponding evaluation questions. In separate workgroups, the definition of these proposals, evidence and evaluation questions were developed. One face-to-face meeting and two meetings via teleconference were necessary to achieve a final document with all the quality standards.

From a proposed structure of sixty-six standards, the titles, definitions, statements and evidence as well as good practices and evaluation questions were established in workgroups with consensus among all of the members (1 - 3). The final version of the self-assessment tool was composed of sixty-eight standards, grouped in twelve quality criteria structured in four dimensions: I Responsibility, II Clients and Stakeholders, III Production Process, and IV Resources.

Quality management requires an evaluation tool and this version, based on a systematic review and consensus, is a useful and practical instrument for developing a handbook by each member of REDETS. An online version of the tool is in process of development.