Digging in real-word electronic database for assessing CDK 4/6 inhibitors adherence in breast cancer patients from Romania.

Introduction: It is imperative for patients to respect the prescribed treatments to achieve the anticipated clinical outcomes, including the outpatients receiving oral anti-cancer drugs such as selective cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i). With the introduction of three CDK 4/6i drugs in the Romanian pharmaceutical market in 2018, our study aimed to evaluate medication adherence and the influencing factors among patients undergoing treatment with palbociclib, ribociclib, or abemaciclib for advanced or metastatic breast cancer. Methods: Medication adherence was assessed using the Proportion of Days Covered (PDC) method, and Spearman correlation analysis was conducted to explore the relationships between adherence, age, gender, and follow-up duration. Results: The study enrolled 330 breast cancer patients, with an average follow-up period of 14.6 ± 12.5 months for palbociclib, 10.6 ± 7.1 months for ribociclib, and 8.6 ± 6.4 months for abemaciclib-treated patients. A small proportion of patients demonstrated non-adherence: 12.8% for palbociclib, 14.6% for ribociclib, and 14.7% for abemaciclib. Among patients receiving palbociclib, there was no significant correlation between adherence, age (rho = 0.07, p = 0.35), or gender (rho = -0.144, p = 0.054). However, a significant correlation was found with the duration of follow-up (rho = -0.304, p < 0.0001). Similar results were observed for patients receiving ribociclib or abemaciclib. Most patients received combination therapy with letrozole (46%) and exemestane (13%) for palbociclib, letrozole (48%) and fulvestrant (19%) for ribociclib, and fulvestrant (39%) and letrozole (27%) for abemaciclib, Discussion: High adherence rates were observed among patients treated with CDK 4/6i drugs, with no significant differences noted among the three drugs in this class. However, the collected patient data was limited, lacking information on adverse reactions that could potentially lead to treatment discontinuation, as determined by the oncologist's decision not to prescribe. Consequently, a comprehensive understanding of all factors contributing to the low adherence levels is hindered.

The Effects of Arginine-Based Supplements on Fatigue Levels following COVID-19 Infection: A Prospective Study in Romania.

The purpose of this study was to examine the effects of two arginine-based supplements on the fatigue level of patients following the COVID-19 infection. This is a prospective study of the SARS-CoV-2-infected patients divided into two groups (according to family physicians' prescriptions, Group 1 of patients were treated with Astenor Energy® containing arginine aspartate, B6 vitamin, biotin and magnesium, and Group 2 of patients were treated with Astenor Forte® containing L-arginine and malic acid). The patients visited their family physicians from October 2021 to January 2022, complaining of physical and/or mental fatigue following the COVID-19 infection. We recorded 505 patients (146 patients in Group 1 and 359 patients in Group 2) and analyzed the fatigue level using the Fatigue Assessment Scale (FAS) through its total (FAS-T), mental (FAS-M) and physical (FAS-P) scores, at baseline and after three months of treatment. There was no difference between the two groups in terms of age (p = 0.265), but more men were included in Group 1 than in Group 2 (p = 0.001). The patients from Group 2 were significantly more likely to be treated at home than those included in Group 1 (89.7% vs. 65.1%, p < 0.0001) because of the lower severity of the COVID-19 infection (asymptomatic or mild: 82.5% vs. 48.7%, p < 0.0001). After 3 months of treatment, patients indicated no fatigue in the higher percentage compared to than at the baseline (68.7% vs. 27.7%), and the fatigue level significantly decreased both in Group 1 (median baseline 33.0 vs. follow-up 17.00, p < 0.0001) and Group 2 (median baseline 25.0 vs. follow-up 17.00, p < 0.0001). These findings suggest that supplements with L-arginine may be proposed as a remedy to restore physical and mental performance affected by the fatigue burden in people with COVID-19 or following the COVID-19 infection.

Diagnostic Accuracy of Machine-Learning Models on Predicting Chemo-Brain in Breast Cancer Survivors Previously Treated with Chemotherapy: A Meta-Analysis.

We performed a meta-analysis of chemo-brain diagnostic, pooling sensitivities, and specificities in order to assess the accuracy of a machine-learning (ML) algorithm in breast cancer survivors previously treated with chemotherapy. We searched PubMed, Web of Science, and Scopus for eligible articles before 30 September 2022. We identified three eligible studies from which we extracted seven ML algorithms. For our data, the χ2 tests demonstrated the homogeneity of the sensitivity's models (χ2 = 7.6987, df = 6, p-value = 0.261) and the specificities of the ML models (χ2 = 3.0151, df = 6, p-value = 0.807). The pooled area under the curve (AUC) for the overall ML models in this study was 0.914 (95%CI: 0.891-0.939) and partial AUC (restricted to observed false positive rates and normalized) was 0.844 (95%CI: 0.80-0.889). Additionally, the pooled sensitivity and pooled specificity values were 0.81 (95% CI: 0.75-0.86) and 0.82 (95% CI: 0.76-0.86), respectively. From all included ML models, support vector machine demonstrated the best test performance. ML models represent a promising, reliable modality for chemo-brain prediction in breast cancer survivors previously treated with chemotherapy, demonstrating high accuracy.

Screening performance of C-reactive protein for active pulmonary tuberculosis in HIV-positive patients: A systematic review with a meta-analysis.

Background: Tuberculosis (TB) is the leading infectious cause of mortality worldwide. In the last years, resistant strains of the etiological agent, Mycobacterium tuberculosis, have emerged, thus demanding more triage tests to identify active pulmonary TB (PTB) patients and to evaluate their disease severity. Therefore, acute-phase reaction serum tests are required for monitoring TB patients, among WHO symptom screening recommendations. C-reactive protein (CRP) is a non-specific inflammatory biomarker that has been recently proposed for TB screening and can be quantitatively analyzed through cost-effective point-of-care assays. A previous meta-analysis found CRP to be highly sensitive and moderately specific for active PTB with confirmed HIV infection. Methods: We performed a meta-analysis update of diagnostic tests, pooling sensitivities, and specificities in order to assess the accuracy of CRP as a potential test for the screening of HIV-associated PTB in outpatients. We searched MEDLINE, Web of Science, and SCOPUS for eligible articles before 19 October 2021. Results: We identified 13 eligible studies with HIV-positive patients with PTB. At a CRP threshold of 10 mg/L, CRP pooled sensitivity was 87% (76%-93%) and pooled specificity was 67% (49%-81%), with an area under the curve (AUC) of 0.858. Using a CRP threshold of 8 mg/L, pooled sensitivity was 82% (72%-89%) and pooled specificity was 82% (67%-92%), with an AUC of 0.879. We found that CRP has a high sensitivity in the screening of PTB in HIV-positive outpatients, consistent with findings reported previously. Conclusions: Regardless of pooled specificity, better results were found using the CRP threshold of 8 mg/L as a test screening of PTB, meeting the need of further approaching specific TB diagnostic methods and reducing resource consumption.

A Systematic Review and Meta-Analysis on Metabolic Bone Disease in Patients with Primary Sclerosing Cholangitis.

Data about the association between primary sclerosing cholangitis (PSC) and metabolic bone disease are still unclear. PSC is a chronic cholestatic liver disease (CCLD) which affects the biliary tract, and it has a highly variable natural history. We systematically searched until 28 February 2022 MEDLINE, Cochrane Central Register of Controlled Trials, the ISI Web of Science, and SCOPUS, for studies in patients with PSC. We identified 343 references to potential studies. After screening them, we included eight studies (893 PSC patients, 398 primary biliary cirrhosis (PBC) patients, and 673 healthy controls) for the present meta-analysis. Pooled analyses found no difference in BMD-LS (Z = 0.02, p-value = 0.98) between PSC patients and healthy controls. BMD-LS was statistically lower in PBC patients than in PSC patients (Mean Difference, MD, 0.06, 95% CI 0.03 to 0.09, p-value = 0.0007). The lumbar spine T-score was higher in the PSC patients compared with PBC patients (MD 0.23, 95% CI 0.04 to 0.42, p-value = 0.02). Given the limited literature available, better designed, and larger scale primary studies will be required to confirm our conclusion.

Calcium and Phosphorus Deficiencies in Patients with Liver Cirrhosis.

Patients with cirrhosis often develop malnutrition and micronutrient deficiencies, leading to a worse prognosis and increased mortality. Our purpose was to assess the prevalence of micronutrient deficiencies especially calcium and phosphorus in patients with decompensated liver cirrhosis (LC). This was a retrospective study including 143 consecutive patients hospitalized for acute decompensation of cirrhosis, most of them with alcoholic etiology along with viral B or viral C and autoimmune induced cirrhosis. A blood test including minerals was performed on admission. Lower serum calcium levels were found in patients with a more severe forms of LC and also the ones diagnosed with viral and alcoholic LC rather than autoimmune induced LC. Peritoneal ascitic fluid was observed in 51 patients with hypocalcemia and only 24 patients with normal calcium levels had fluid accumulation. Low levels of phosphorus were noted in patients with a more severe form of LC (chi-square: 20.2504; p-value 0.000446). Ascitic fluid was found in patients with low values of phosphorus as well as in those with hypocalcemia (chi-square 5.235; p-value 0.022137). In conclusion, this study confirmed that patients with advanced liver disease had lower values of calcium and phosphorus and a more severe form of LC can be associated with hypocalcemia and hypophosphatemia.

Osteoporosis Assessment among Adults with Liver Cirrhosis.

Osteopenic bone disease occurs frequently in patients with chronic liver cirrhosis, which most frequently presents with hepatic osteodystrophy. Thus, the relationship between nutritional status and bone mineral density has been poorly measured in liver cirrhosis. This single-center study consisted of a group of 70 patients diagnosed with liver cirrhosis. The nutritional status was evaluated with the Controlling Nutritional Status index, and volumetric vertebral bone mineral density was measured with quantitative computed tomography. Among the 70 patients included, osteopenia and osteoporosis were found in 71% and 24.3%, respectively. Malnutrition assessed with the Controlling Nutritional Status index was observed in 56 (80%) patients and was more frequent in alcoholic cirrhosis patients than viral cirrhosis patients (87.24% vs. 65.22%). Significant positive correlation with Controlling Nutritional Status score was found with Model for End-Stage Liver Disease (rho = 0.576, p-value < 0.0001), Child−Pugh score (rho = 0.670, p-value < 0.0001), International Normalized Ratio (rho = 0.517, p-value = 0.001), aspartate aminotransferase (rho = 0.293, p-value = 0.045), and bilirubin (rho =0.395, p-value = 0.02). Among the liver cirrhosis patients, 15 had osteoporosis and 49 had osteopenia at the lumbar spine (L1-L4 vertebrae), as determined by bone mass density via quantitative computed tomography. A non-significant relationship between Controlling Nutritional Status index-assessed nutritional status and bone mass density was documented. Regarding osteoporosis, no differences were found between the viral and alcohol types of liver cirrhosis patients (p-value = 0.870). Age, obesity, grade of varices, Child−Pugh score, and Model for End-Stage Liver Disease score were associated with osteoporosis in patients with liver cirrhosis.

Pharmacist's Perspectives on Administering a COVID-19 Vaccine in Community Pharmacies in Four Balkan Countries.

Community pharmacists expanded their roles and engaged in vaccination services in many countries around the world, but not in Balkan countries. This research aimed to assess the perceptions of pharmacists on involvement in the coronavirus disease (COVID-19) vaccine administration in four Balkan countries (Albania, Bulgaria, Romania, and Serbia). A cross-sectional survey was conducted using an online questionnaire that was distributed to community pharmacists across these countries between February and March 2021. A total of 636 community pharmacists were included in the analysis of the survey. The willingness to administer vaccines for COVID-19 (or other vaccines well established in the practice, like a flu vaccine) in community pharmacies is significantly different among the countries: the pharmacists from Albania were more willing to administer vaccines. The factors associated with the eagerness to vaccinate are almost the same among the countries: the lack of training in the faculty classes and the lack of a special place where to administer vaccines. Additional significant factors were found in Bulgaria (pharmacists from independent pharmacies wanted more than the pharmacists working in chain pharmacies to administer vaccines) and in Serbia (male pharmacists agreed more with administering vaccines than female pharmacists). Further national reforms are needed for adopting the expanding role of community pharmacists.

Development and Validation of a Questionnaire to Measure Medication Adherence to Direct-Acting Agents in Patients with Hepatitis C.

This study aims to develop a new self-report tool (HCV-AD) measuring adherence factors, intentional or unintentional, during Hepatitis C Virus (HCV) treatment with direct-acting antivirals (DAA) aiming to achieve high efficacy, otherwise resulting in drug resistance and treatment failure. Two phases were conducted: in the first phase, items were generated based on an extensive literature review, and, in the second phase, a prospective cohort study was conducted using HCV patients from Gastroenterology Department from University County Hospital of Craiova, Romania (n = 222), to evaluate the validity and reliability of the questionnaire. A number of 19 items were generated following a systematic review and through expert opinion. The internal consistency reliability was evaluated using Cronbach's alpha. The construct validity was assessed using correlations with two other instruments: visual analog scale (VAS) and medication possession ratio (MPR). The final questionnaire (HCV-AD10) was derived through exploratory factor analysis, with 82% of total variance explained. This instrument appeared as a reliable and valid measure for medication adherence, with Cronbach's alpha (0.867) and significant high positive correlations between adherence scores calculated with HCV-AD10 and VAS (ρ = 0.61, p < 0.001) or with HCV-AD10 and MPR (ρ = 0.75, p < 0.001). This research would make a worthwhile contribution to HCV management.

Do Advanced Therapies Have a Future in the Low- and Middle-Income Countries - The Case of Bulgaria, Romania, and Poland.

Introduction: The significant therapeutic potential of the advanced therapies (ATs) has predetermined the increased interests in their development mainly in the context of rare diseases most of which are genetically determined. However, there are still many challenges in front of the health insurance funds related to the cost-effectiveness and budget impact issues of these therapies. Our aim was to review and analyze the potential of low- and middle-income countries for health technology assessment (HTA) of advanced therapies focusing on Bulgaria, Romania and Poland as reference countries. A literature review of the existing good practices related to HTA of advanced therapies across the world and comparison with the national reality were performed. A list of challenges and issues from the point of view of the payer institution of all analyzed countries was performed. Pilot recommendations on how to overcome the barriers were created based on the existing practices and the potential of the national system. Discussion: 15 out of 80 articles identified in PubMed were found as applicable to the study scope as most of them were published in the period 2019-2021. Undoubtedly, the main challenges correspond to the high treatment costs, the uncertainty in clinical effectiveness, and poor HTA methodological approaches applicable for ATs worldwide. The issues identified for low and middle-income countries are similar having as well the lack of enough qualified health economists for the purposes of assessment and appraisal of HTA dossiers of the advanced therapies, lack of adequate existing separate financial programs for those therapies, and not preparedness of the health system and the society as a whole for such therapies. Conclusions: Despite the difficulties and challenges, the advanced therapies can be defined as a futuristic therapy for which great discoveries are yet to come. Therefore, each country should consider the implementation of reliable and nationally oriented programs for HTA and adequate financial coverage of these therapies.

Can Incobotulinumtoxin-A Treatment Improve Quality of Life Better Than Conventional Therapy in Spastic Muscle Post-Stroke Patients? Results from a Pilot Study from a Single Center.

Post-stroke spasticity frequently occurs in patients with stroke, and there is a need for more quality-of-life assessments for different therapies. We evaluated for the first time in Romania the quality of life among patients with post-stroke spasticity, comparing two therapies over a 6-month period: botulinum toxin type A (BOT) with conventional therapy (CON). We also assessed the reduction of spasticity and functionality secondary to the increase in the mobility in upper limbs. This study was based on a prospective, randomized design, including subjects with post-stroke spasticity (N = 34; 34-80 years of age): in the CON arm, patients received therapy against muscle spasticity and physiotherapy, and, in the BOT arm, patients received incobotulinumtoxin-A and additionally conventional treatment, if required. Among 34 treated subjects in the two arms, the quality of life was significantly higher after BOT therapy (p < 0.001), represented by improvement in movement (p < 0.001), usual activities (p = 0.018), and distress (p < 0.001). Improvements in muscle tone (Ashworth Scale) over 6 months of treatment period were greater in the BOT arm (100%) than in the CON arm (11.8%). These preliminary results suggested that incobotulinumtoxin-A increased quality of life by improving movement, daily activities, mental health, and muscle tone more effectively than conventional therapy and could form a basis for future comparator studies.

Prediction of Treatment Outcome with Inflammatory Biomarkers after 2 Months of Therapy in Pulmonary Tuberculosis Patients: Preliminary Results.

Pro-inflammatory mediators play an important role in the pathogenesis of pulmonary tuberculosis. Consecutively, 26 pulmonary tuberculosis patients were enrolled in our study based on the exclusion criteria. We have used Spearman's correlation analysis, hierarchical clustering and regression modelling to evaluate the association of 11 biomarkers with culture status after antituberculosis treatment. The results of our study demonstrated that six inflammatory biomarkers of 11, C-reactive protein (CRP), white blood cells (WBC), neutrophils, interferon gamma inducible protein 10, C-reactive protein (CRP) to albumin ratio (CAR) and neutrophil to albumin ratio (NAR), were significantly associated with culture negativity. The predictive ability of a composite model of seven biomarkers was superior to that of any single biomarker based on area under the receiver operating characteristic curve (AUC) analysis, indicating an excellent prediction efficacy (AUC:0.892; 95% CI:0.732-1.0). We also found that the highest significant trends and lower levels of CRP and IP-10 were observed in the two-month treated tuberculosis (TB) patients. We believe that our study may be valuable in providing preliminary results for an additional strategy in monitoring and management of the clinical outcome of pulmonary tuberculosis. Using a panel of predictors added a superior value in predicting culture status after anti-TB therapy.

Telemedicine Chronic Viral Hepatitis C Treatment during the Lockdown Period in Romania: A Pilot Study.

The COVID-19 pandemic is currently delaying the process of chronic hepatitis C (HCV) eradication, since most of the chronic diseases are neglected. Thus, there is a need for alternative programs for HCV therapy implementation and disease monitoring. Our aim was to provide a multidisciplinary approach, so that HCV-infected patients from distant locations may benefit from HCV antivirals during the COVID-19 outbreak and within the lockdown period in Romania. Previously diagnosed HCV patients willing to participate in this telemedicine pilot study were included. Patient characteristics and medical adherence were assessed and compared to the year preceding the pandemic. We proposed a multidisciplinary approach by using a telemedicine program for HCV therapy monitoring. Patients also received a satisfaction questionnaire after delivering the sustained virologic response (SVR) result. A total of 41 patients agreed to participate in this study. The medication adherence was 100% for patients included in the telemedicine group, with a statistically significant difference from the medication adherence of the patients treated in 2019. The satisfaction item score was 4.92 out of 5 and our results (r = -0.94, p < 0.0001) suggested that older patients embraced the telemedicine program less, but with the same success in terms of SVR (100%) and medication adherence (100%). Our pilot study offers the first example of a telemedicine program in Romania for HCV therapeutic management. During the lockdown period, telemedicine has served as a reliable tool and novel alternative for conventional monitoring of patients treated with direct antiviral agents and should be further considered even following the pandemic.

Influence of COVID-19 on Health-Related Quality of Life and the Perception of Being Vaccinated to Prevent COVID-19: An Approach for Community Pharmacists from Romania and Bulgaria.

Community pharmacists are essential front-line health workers, involved in relieving the COVID-19 burden. Their health-related quality of life status needs to be assessed, as lower levels could affect their functioning. In order to evaluate the current status of community pharmacists' quality of life from Romania and Bulgaria during the COVID-19 pandemic, and to identify factors associated with their decision on being vaccinated to prevent COVID-19, an online survey involving 395 community pharmacists was conducted from 15th July 2020 to 15th August 2020. The 15D instrument was used for quality-of-life assessment. The pharmacists' recommendations for vitamin C and D intake during the COVID-19 pandemic were also analyzed in order to promote future training programs for community pharmacists. Descriptive statistics, comparative analyses between pharmacists from Romania and Bulgaria, and multiple correlation analyses were performed on the collected data. Significant differences were observed for the level of quality of life between the two groups of pharmacists according to their age; smaller values, directly correlated with their age (total 15D score and age: Spearman r = 0.168, p = 0.022), were obtained for Bulgarian pharmacists regarding sleeping, usual activities, mental function, discomfort and symptoms, depression, distress. The perception of being vaccinated did not differ between Romanian and Bulgarian pharmacists, as almost 50% agreed to vaccination (p = 0.7542). Their willingness to vaccinate was correlated with vitamin D usage (p = 0.0134), rather than with vitamin C (p = 0.4157). No other significant associations were found between willingness to get vaccinated to prevent COVID-19 and other characteristics (age, gender, income, quality-of-life markers). Evidence-based interventions are required to enhance the health-related quality of life of community pharmacists involved in the first line of the COVID-19 pandemic.

Personal Autonomy as Quality of Life Predictor for Multiple Sclerosis Patients.

Multiple sclerosis (MS) is a chronic, severe disease, characterized by a progressive alteration in neuronal transmission, which decreases personal independence and quality of life (QoL). This study aimed to investigate the relationship between QoL and personal autonomy in patients with MS, as well as its correlation with age, educational level, and diseases severity. Twenty-six MS patients were followed-up for six months. All patients completed the 15D questionnaire two times: at T0, when they started a new treatment, and at T1 after six months of treatment. At the end point, all patients completed the Personal Autonomy Questionnaire. The average patient age was 43 years (SD = 10), and 89% of them were female. The mean severity and duration of MS were 3.5 (SD = 1.75) and 9.5 (SD = 5.1), respectively. The average QoL of MS patients at T0 was 0.66 (SD = 0.18), and that at T1 was 0.71 (SD = 0.16). The scores of patients with different types of MS, i.e., relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS), were compared. SPMS patients were older than RRMS patients (mean age 47.5 vs. 39.7 years; p = 0.032), and more RRMS patients were working (0.014). SPMS patients described the same QoL and personal autonomy as RRMS patients. Results from bivariate correlation analyses showed a significant relationship between QoL and age, education, and severity of MS. Also, the analysis showed no significant correlation between QoL and personal autonomy.

Possible Involvement of Vitamin C in Periodontal Disease-Diabetes Mellitus Association.

Ascorbic acid (vitamin C) is an important water-soluble vitamin found in many fruits and vegetables. It has well-documented beneficial effects on the human body and is used as a supplement, alone or in combination with other vitamins and minerals. Over recent years, research has focused on possible new therapeutic actions in chronic conditions including periodontal disease (PD). We conducted a systematic review on clinical trials from four databases (PubMed, Clinical Trials, Cochrane, Web of Science) which measured plasmatic/salivary levels of ascorbic acid in PD-diabetes mellitus (DM) association. Six studies were included in our review, three of them analyzing patients with different grades of PD and DM who received vitamin C as a treatment (500 mg vitamin C/day for 2 months and 450 mg/day for 2 weeks) or as part of their alimentation (guava fruits), in combination with standard therapies and procedures. Decreased levels of vitamin C were observed in PD patients with DM but data about efficacy of vitamin C administration are inconclusive. Given the important bidirectional relationship between PD and DM, there is a strong need for more research to assess the positive effects of ascorbic acid supplementation in individuals suffering from both diseases and also its proper regimen for these patients.

Cost-Utility Analysis of Incobotulinumtoxin-A Compared With Conventional Therapy in the Management of Post-Stroke Spasticity in Romania.

Objectives: In Romania, the strokes' incidence is of 61,500 per year and improving upper limb function is the essence in rehabilitation after a stroke to maximize the patient quality of life and reduce disability. In this study, it is compared the cost-effectiveness of the treatment of post-stroke upper limb spasticity with incobotulinumtoxin-A (INCO), with or without electromyographic control, against the conventional therapy programme alone (CON). Methods: A Markov state transition model was developed to effectuate a cost-utility analysis (CUA). Measurements of health-related quality of life were derived from relevant clinical trials. Utility values for quality of life by response status were derived from the Short-Form-12 (SF-12) Health Survey data from a published study. The incremental cost-effectiveness ratio (ICER) of INCO (fixed, every 12 weeks) against CON was calculated in Ron per quality-adjusted life-year (QALY) gained for both therapies. Costs and outcomes were discounted using different scenarios at 3% and 5% per year with a time horizon of 3 and 5 years because Romanian legislative norms don't specify the discount rates and time horizon for pharmacoeconomic analysis. Probabilistic sensitivity analyses (PSA) were managed on the base case with distributions attributed to the frequency of repeat dosing and utility valuation of the responder and the non-responder for health utilities derived from both mental and physical health state. Results: Compared with CON, in all 4 scenarios, therapy with INCO had an incremental cost-effectiveness ratio (ICER) of less than 950 Euro per QALY gained (1 Euro = 4.7 Ron). INCO proved to be more favorable treatment option than CON in the treatment of upper limb spasticity in Romania. Despite costs being higher for patients treated with INCO, this treatment has more advantageous Incremental Cost-Effectiveness Ratio. Conclusions: This therapy should be taken into account when considering rehabilitation options because it is highly cost-effective at < EURO 1,000/QALY gained, a very low WTP (Willingness To Pay) threshold. INCO proved to be a disruptive innovation because it is a new and more effective treatment, and, in the end, much higher in quality of life for patients with post-stroke upper limb spasticity.