Percutaneous ethanol injection (PEI) is a valuable treatment for several health conditions. However, its beneficial and harmful effects in patients with thyroid nodular pathology and metastatic cervical adenopathies have not been assessed in a systematic review.

A systematic review of available scientific literature on the safety, effectiveness, and cost effectiveness of PEI in thyroid nodular pathology and metastatic cervical adenopathies was performed according to Cochrane Collaboration methods and reported in accordance with the PRISMA statement. A cost-minimization analysis was carried out using a decision tree model. Assuming equal effectiveness between two minimally invasive techniques (PEI and radiofrequency ablation [RFA]), the model compared the costs of the alternatives with a horizon of six months from the perspective of the Spanish National Health System.

Three randomized controlled trials (n=157) evaluating PEI and RFA in patients diagnosed with benign thyroid nodules, 96 with predominantly cystic nodules and 61 with solid nodules, were identified. No evidence was found on other techniques or thyroid nodular pathology. No statistically significant differences were observed between PEI and RFA in proportion of volume reduction, symptom score, cosmetic score, therapeutic success, or major complications. No economic evaluations were identified. The cost-minimization analysis estimated the cost per patient of the PEI procedure to be EUR326, compared with EUR4,781 for RFA, with an incremental difference of −EUR4,455.

There are no differences between PEI and RFA in terms of safety and effectiveness, but the economic evaluation determined that the former option is cheaper.

Burkitt lymphoma (BL) is a rare and highly aggressive subtype of non-Hodgkin’s lymphoma. Several studies have identified prognostic factors (PFs) for disease progression and mortality among adults with BL. However, there is no consensus on risk stratification based on PFs. This study aims to identify, critically assess, and synthesize the available evidence on PFs for survival in adults with BL.

A systematic review of the literature was conducted. MEDLINE, Embase, and CENTRAL were searched from inception to 22 February 2022. Randomized or non-randomized clinical trials and longitudinal observational studies were eligible for inclusion. Reference screening, data extraction, and risk-of-bias assessment using the Quality in Prognosis Studies (QUIPS) tool for prognostic factor studies were conducted independently and in duplicate. Publication bias was examined by visual inspection of funnel plots. Effect measures and the corresponding 95% confidence intervals were pooled with an indirect variance estimation in meta-analyses using Review Manager 5, and sensitivity analyses were conducted. Certainty of evidence was assessed using GRADE.

The search identified 1,119 references after duplicate removal. Of these, 76 potentially relevant papers were selected for full-text assessment and 36 studies (N=10,882) reported in 39 articles were eligible for inclusion. Older age, higher performance status, and central nervous system involvement were associated with poorer overall survival (OS) and progression-free survival (PFS). Black patients exhibited significantly lower OS and relative survival. Bone marrow involvement and higher albumin levels were associated with poorer OS. Treatment with rituximab and treatment with methotrexate were associated with better OS and PFS. No significant differences in survival were found for HIV status, sex, and risk stratification.

This study, framed within a collaboration with European Reference Network EuroBloodNet, provides a comprehensive and methodologically rigorous evidence review on PFs in adults with BL. Several significant associations of PFs and survival estimates were observed, providing data to inform treatment decisions and to improve patient care.

Patients with antiphospholipid syndrome (APS) present a significant risk of thrombotic events or morbidity during pregnancy, associated with the presence of persistently positive antiphospholipid antibodies (aPL). The risk stratification is crucial to adopt primary prophylaxis measures. With this objective, assays for the in vitro detection of anti-domain 1 β2 glycoprotein I (aD1 IgG) antibodies by chemiluminescence immunoassay (CLIA) have been developed.

We conducted a systematic review with meta-analyses on the effectiveness of incorporating aD1 IgG detection by CLIA for the identification of patients with APS at high risk of thrombosis or morbidity during pregnancy. A cost analysis was also conducted using a decision tree model from the perspective of the Spanish National Health System and a time horizon of three months. We ran extensive sensitivity analyses. Twelve diagnostic performance studies with a total of 3,570 patients were selected.

The sensitivity and specificity of aD1 IgG added to the conventional aPL criteria for obstetric and thrombotic manifestations ranged from 15 to 16 percent, and from 94 to 97 percent, respectively. The sensitivity of the detection of aD1 IgG in isolation for thrombotic and obstetric manifestations was 29 and 48 percent, and specificity was 60 percent, respectively. The GRADE quality of evidence was very low due to the risk of bias and indirectness issues. The incorporation of the aD1 IgG detection involves a higher cost per patient than the usual clinical practice, with an incremental difference of EUR24.04 (USD26.01).

Despite its potential, the incorporation of the aD1 IgG detection by CLIA as an additional test to the determination of classical aPL for the identification of patients with APS at high thrombotic or obstetric risk may not be feasible due to the very low available evidence on diagnostic performance and increased costs.

The genicular artery embolization (GAE) procedure has been recently adopted for the management of pain secondary to inflammatory diseases of the locomotor apparatus. The number of studies assessing its use in patients with knee osteoarthritis (KO) has been increasing in recent years.

We included two randomized controlled trials (RCTs) evaluating the use of GAE in patients with chronic pain secondary to KO. A cost analysis was also conducted to compare the costs of GAE and standard treatment from the perspective of the Spanish National Health System over a time horizon of one year. The potential improvement in quality-adjusted life-years necessary to consider GEA as cost effective for this indication was estimated. We also ran extensive sensitivity analyses.

Estimates for pain showed contradictory results, and no significant differences were observed between the two treatments with respect to overall function, health-related quality of life (HRQoL), and need for pain medication. No serious complications or major adverse events were observed. The quality of evidence was assessed by GRADE as moderate to low. The cost analysis showed that GAE results in an incremental cost of EUR3,432.37 per patient. Sensitivity analyses revealed a wide range within which the incremental cost can vary.

There are insufficient data to discern any differences between GAE and standard treatment for patients with KO in terms of pain, function, HRQoL, need for analgesics, and rates of adverse events and complications. Larger RCTs are required to evaluate the effect of GAE in patients with chronic pain secondary to KO and to determine whether its additional cost is warranted.

A consortium of five Spanish health technology assessment (HTA) agencies conducted the European Reference Networks Guidelines Programme for the development, appraisal, and implementation of clinical practice guidelines aiming to support clinical decision-making in the field of rare diseases (RDs). In response to this objective, methodologists and information specialists conducted systematic reviews (SRs). This study aims to explore the barriers/facilitators they encountered.

A survey was designed to elicit HTA agencies’ experience in developing SRs on RDs. Information was collected on the number of SRs conducted and the types of RDs and clinical questions addressed. In addition, they were asked to identify barriers and facilitators for each stage of the review (from the definition of PICO [population, intervention, comparator, outcome] components of the question to the issuing of recommendations). Finally, they were asked for process improvement suggestions. The survey was distributed by email and completed online. A thematic analysis was conducted to identify the issues identified at each stage of SR.

A total of 111 SRs were conducted on 35 RDs. Most clinical questions were about diagnosis and treatment. The main barriers identified were lack of MesH (Medical Subject Headings) terms associated with the conditions, non-representative abstracts and keywords, lack of relevant information in the body of the articles, and reported data not allowing for quantitative syntheses or recommendations to be made. Facilitating aspects included Orphanet’s specific source of RD documents and having expert clinicians in the working groups who were also involved in all steps of the SR.

Conducting SRs in the field of RDs is challenging. Authors of primary studies are encouraged to be more exhaustive in reporting the results. More research focused on the SR methodology in RDs is necessary to address their particular characteristics and obtain robust results. It is crucial to collaborate with reference networks to address RDs, where the evidence is scarce.

Telemedicine has been introduced in health services, but uncertainties about the real value of this strategy in the management of neurological diseases remain.

A systematic review was undertaken of available scientific literature on the safety, effectiveness, and cost effectiveness of telemedicine combined with in-person visits, compared with usual care, for the treatment and follow-up assessment of patients with neurological diseases. The overall effect size for each neurological disease was estimated using meta-analysis. An economic analysis was performed from the societal and Spanish healthcare system perspectives.

Two economic studies were included for cost effectiveness and 25 randomized controlled trails (n=8,976 patients) were included for the effectiveness and safety assessment (11 on cerebrovascular diseases, four on Parkinson’s disease, three on multiple sclerosis, two on epilepsy, and one each on brain damage, dementia, spina bifida, migraine, and cerebral palsy). The types of telemedicine evaluated included: virtual visits (11 studies); telerehabilitation (seven studies); telephone calls (three studies); smartphone apps (two studies); and online software for computers (two studies). Subgroup analysis by type of telemedicine indicated no discernible effect for telemedicine combined with in-person visits on most of the outcomes analyzed for the various neurological diseases. Given the heterogeneity of diseases, types of telemedicine, and the results observed, a cost-minimization analysis was conducted. Combining telemedicine with in-person visits would cost EUR 2.55 per patient from the perspective of the healthcare system, but it would result in cost savings (EUR 27.34 per patient) from the societal perspective.

The safety and effectiveness of combining in-person visits with telemedicine was similar to that of usual care, but it could be a cost-saving strategy in Spain from a societal perspective.

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.