Voice problems are common following radiotherapy for laryngeal cancer. Few studies exist covering the effect of voice rehabilitation, and no previous studies exist regarding the cost of said rehabilitation. This randomized controlled study aimed to analyze the cost-effectiveness of voice rehabilitation after radiotherapy for patients with laryngeal cancer.n = 32) or no voice rehabilitation (n = 34). The patient outcome was measured as quality-adjusted life years (QALYs). The index range between 0 and 1, where 0 equals death and 1 represents perfect health. The QALYs were assessed with the European Organization for Research and Treatment of Cancer questionnaire QLQ-C30 mapped to EuroQoL 5 Dimension values. The cost of rehabilitation and other healthcare visits was derived from hospital systems. The patients reported the total amount of sick leave days during the first 12 months following radiotherapy. The cost-effectiveness of the voice rehabilitation was compared with no rehabilitation intervention based on the incremental cost-effectiveness ratio.A total of 66 patients with laryngeal cancer with follow-up data 12 months post-radiotherapy were included. Patients were randomized into receiving either voice rehabilitation  which indicates that the voice rehabilitation is a cost-saving alternative compared to no rehabilitation due to lower costs and a slightly better health outcome. From a healthcare perspective, the voice rehabilitation indicates a cost 60,800 €  per gained QALY.From a societal perspective, i.e., including the costs of production loss, voice rehabilitation compared to no voice rehabilitation following radiotherapy for laryngeal cancer seems to be cost-saving. When analyzing only the healthcare costs in relation to health outcomes, voice rehabilitation indicates an incremental cost of 60,800 € per gained QALY, which is just above the threshold of the maximum willingness to pay level. Vocal dysfunction is a common side effect following radiotherapy for laryngeal cancer –3. StudiAll patients diagnosed with laryngeal cancer in the Region Västra Götaland are discussed on a weekly multidisciplinary tumor board, where treatment options are discussed and decided for each patient. Between the years 2000 and 2011, with an interruption of 2 years, the patients who were to receive curatively intended radiotherapy ± chemotherapy were asked to participate in the study. Inclusion criteria were sufficient cognitive ability and sufficient knowledge of the Swedish language in order to fill out study questionnaires. Comorbidity was measured with the Adult Comorbidity Evaluation (ACE-27) , 22.The computerized randomization followed Pocock’s sequential randomization method  for optiVoice rehabilitation was given between 1 and 6 months post-radiotherapy, by speech-language pathologists. The rehabilitation protocol consisted of 10 occasions over the course of 10 weeks, approximately 30 min per rehabilitation session. The sessions included a specified set of exercises of breathing, relaxation, and phonation exercises, both indirect and direct therapy techniques. The patients were encouraged to exercise at home between sessions. The protocol has been described in detail elsewhere .n = 45) or hyperfractioned (n = 21). Conventionally, fractionated therapy was given once daily in 2–2.4 Gy fractions to a total dose of 64.6–68 Gy. Hyperfractioned therapy entailed 1.7 Gy doses that were given twice daily to a total dose of 64.6 Gy. Most patients with T2-T4 tumors also received irradiation to regional lymph nodes to a total dose of 40.8–46 Gy. Three patients received chemotherapy in addition to radiotherapy.Radiotherapy was given in accordance with regional treatment guidelines, either as conventionally fractioned . QALY is a measurement that combines health-related quality of life (HRQL) and life expectancy in one index. The index range between 0 and 1, where 0 equals death and 1 represents perfect health. Thus, 1 QALY corresponds to 1 year of perfect health . Life exn = 26), where the patients were asked about the amount of sick leave during the 12 months following radiotherapy.The costs were categorized as either direct healthcare costs or loss of production. The cost of cancer treatment is not included in the analysis. All costs regarding hospital admission days and hospital visits over the 12 months following radiotherapy were derived from the hospital charts and hospital administration and were calculated for each patient. The loss of production was based on the number of sick leave days after radiotherapy treatment and during 1-year follow-up. The loss of production was valued by the human capital approach assuming that production loss is valued at market price , i.e., gCosts are presented in euros (€/EUR) and in Swedish kronor (SEK) using 2013 exchange rates for conversion to Swedish kronor (SEK 8.98 = 1 EUR).The cost-effectiveness of the voice rehabilitation was compared with no rehabilitation intervention based on the incremental cost-effectiveness ratio (ICER). The ICER is defined by the difference in cost between the two alternatives, divided by the difference in their effects. Thus, the ICER could be interpreted as the incremental cost associated with 1 additional QALY. The ICER is calculated as follows:The cost-effectiveness analyses are presented from two perspectives, the societal perspective , and the healthcare perspective . The costs and health outcomes were not discounted due to a 1-year time horizon.x- and y-axes. The maximum willingness to pay was set to 55,000 €  according to the Swedish National Board of Health and Welfare [A non-parametric bootstrapping was conducted to demonstrate the uncertainties surrounding the ICER. The bootstrapping was conducted using 1000 bootstrap replicates. The results of the bootstrapping are shown using a cost-effectiveness plane in Fig.  Welfare .Fig. 1CoThere is no existing algorithm for mapping EORTC QLQ-C30 to EQ-5D values for patients with laryngeal cancer; thus, a deterministic sensitivity analysis was carried out with the existing algorithms for other types of cancer –35.U test was used due to skewed data. All the analyses were carried out in SPSS software .The variable distribution was presented as mean and standard deviation (95% CI) for continuous variables and as number and percentage for categorical variables. All significance tests were two-sided and conducted at the 5% significance level. For comparison between groups, the non-parametric Mann-Whitney n = 2), laryngectomy (n = 4), and patient choice (n = 5).A total of 194 patients were assessed for eligibility in the study, and 163 patients met the inclusion criteria. Of these, 89 patients (55%) chose to participate in the study and were allocated to voice rehabilitation group or control group. Twelve patients discontinued their participation before their first follow-up, leaving a total of 77 patients (87%). An additional 11 patients discontinued their participation before the 12-month follow-up, leaving 32 patients in the voice rehabilitation group and 34 in the control group. Reasons for discontinuation were missed appointment  and the mean healthcare cost for the group with no rehabilitation was 17,173 € with a range from 0 € to 65,422 € .The QALYs were calculated as the area under the curve by using time-weighted QALY-weight taking account of the time spent in each health state Table . The meaThe cost-effectiveness results are shown in Table A non-parametric bootstrapping with 1000 bootstrap replicates was conducted to assess the uncertainty in the cost-effectiveness ratio. The results are presented in a cost-effectiveness plane , there is a 66% probability that voice rehabilitation is cost-effective compare to no rehabilitation. From a healthcare perspective and at a threshold of 55,000 € , there is a 62% probability that voice rehabilitation is cost-effective compared to no rehabilitation.Table This study aimed to investigate the cost-effectiveness of a structured voice rehabilitation protocol following radiotherapy for laryngeal cancer. Previous studies have shown that the effects of voice rehabilitation include improved HRQL, which prevents a deterioration of perceived roughness and better self-perceived communicative function , 18, 20.The gain from a societal perspective was the decreased number of sick leave days from an average of 85.72 with no rehabilitation to 67.66 with voice rehabilitation. The number of sick leave days in the group without voice rehabilitation is similar to a study by Cohen et al., where laryngeal cancer patients had a mean of 97.89 sick leave days over a 12-month period . AlthougAs previously stated, no mapping algorithm exists to convert EORTC QLQ-C30 data to utility scores for this patient group. The authors therefore looked at mapping algorithms for different patient groups, and the main algorithm chosen was the full model by Proskorovsky et al. . This moAdditionally, the utility scores are mapped from the EORTC QLQ-C30, which might not be the most appropriate questionnaire to find the differences that are expected following voice rehabilitation. The EORTC QLQ-C30 is developed for measuring HRQL in cancer patients in general, and previously, the laryngeal cancer population has been found to demonstrate good HRQL at 1 year following treatment when using the EORTC QLQ-C30, with values comparable to the values of a normative population , 39. HowThe main strength with this cost-effectiveness analysis is that the data were collected prospective alongside a clinical trial and that the data are patient reported. A limitation to this study is the small patient sample with large variation of healthcare utilization and production loss, as well as that the power calculation for sample size was performed for voice outcomes only, and not costs and QALYs. Another limitation is that the sick leave days were derived mainly from the patients themselves, who were asked to state, in months, how much sick leave they had from work with increased risk of recall-bias. The number of sick leave day would probably be more accurate if this had been collected more precise, i.e., if the patient stated number of days or collected from registries. However, in this case, it was not possible, possibly leading to some bias regarding the total number of days of sick leave.Voice rehabilitation compared to no voice rehabilitation following radiotherapy for laryngeal cancer seems to be cost-saving in a societal perspective, i.e., when including both healthcare costs and the costs of production loss. When analyzing only the healthcare costs in relation to quality outcomes, voice rehabilitation indicates a cost per QALY which is just above the maximum willingness to pay level. Despite this, this study provides important information to decision makers regarding the benefits of voice rehabilitation in a societal perspective.


Although South Africa (SA) is facing a high prevalence of HIV infection, there is no literature from this region on a link between Bell’s palsy and HIV. The aim of this study was to identify the occurrence of Bell’s palsy in relation to demographics, seasons and HIV status among black South Africans.This retrospective cohort was conducted among adult black patients, without Bell’s palsy in 2003, presenting to the neurology outpatients department at Dr. George Mukhari Academic hospital, Pretoria, South Africa, between 2004 (study baseline) and 2012 (end test). Gender, age, HIV status, and seasons were potential predictors of Bell’s palsy using Cox regression model and Kaplan Meier curves.n = 311) experienced Bell’s palsy onset by the end of the study. In univariate analysis, male gender , age less than 30 years , HIV seropositivity .From the baseline of 1487 patients, 20.9% (n = 136/450) vs. incidences during other seasons with Intermediate values during Summer (25.3% n = 136/450) and Autumn (20.7% n = 64/308) and the lowest incidence in Spring (23.7% n = 16/353) P < 0.0001) were predictors of Bell’s palsy. In multivariate analysis at adjusting for gender, the most significant and independent predictors of incident Bell’s palsy were HIV seropositivity , winter  vs. other seasons, and younger age < 30 years  vs. older age groups.The highest incidence in winter (30.3% Seasonality, younger age and HIV positivity are important and independent risk factors of Bell’s palsy. Education and awareness programs on the possible effects of HIV and seasons on the development of Bell’s palsy are necessary. This would lead to a better understanding and even a possible development of avoidance measures for this condition amongst young black South Africans. Bell’s palsy is an acute idiopathic lower motor neuron facial palsy, not associated with pyramidal signs. The seasonal occurrence of Bell’s palsy has been debated for more than two centuries, first suggested by Nicolaus Friedreich in 1798 . Indeed,This retrospective cohort was conducted among adult black patients, without Bell’s palsy in 2003, presenting to the neurology outpatient department at Dr. George Mukhari Academic hospital, Pretoria, South Africa, between 2004 (study baseline) and 2012. Gender, age, HIV status, and seasons were potential predictors of Bell’s palsy. Bell’s palsy was defined by an acute idiopathic  peripheral facial weakness with no pyramidal signs. Younger and older ages were defined by median age of 30 years. Cold seasons included autumn / fall and winter, while warm seasons included spring and summer. Autumn was defined as a transitional season from summer leading to winter while spring was defined as a transitional season from winter leading to summer.P - value < 0.05 was regarded as statistically significant. The statistical software IBM * SPSS version 22 for Windows  was used for all analyses.Categorical variables were presented as proportions (%), while the continuous variable (age) was expressed as the median. In univariate analysis, relative risk (RR) of incident Bell’s palsy and its 95% confidence interval (CI) was calculated (Mantel- Haenszel test). In multivariate analysis, the Cox regression model was computed to quantify the association (hazards ratio = HR with its 95% CI) between exposures to univariate potential risk factors, and the multivariate risk of Bell’s palsy after adjusting for confounding factors. Differences between exposed and non-exposed arms were investigated and Kaplan-Meier survival curves were generated using the log rank test. Table A majority of HIV positive females with Bell’s palsy were not on ARV treatment (60%) whilst the inverse was true for males (60% on ARV treatment). There were no abnormalities of cognition demonstrated  in all patients with Bell’s palsy with no difference in mental performance between those on ARVs and ARV naïve patients.The present study demonstrated univariate and multivariate associations between younger age, male gender, cold seasons, HIV infection, and incident Bell’s palsy among black South African patients. These specific findings confirmed or disputed data reported from the literature as will be further elaborated.Bell’s palsy can occur at any age but the question has been which age groups are most vulnerable to the condition. These vulnerable age groups could shed light further on the underlying pathophysiology of the condition. Our study showed a peak at the age less than 30 years. This is at variance with various previous studies in Europe and Asia which found Bell’s palsy to peak in the fourth and fifth decade –11.A study from the Benghazi region of Libya showed people above the sixth decade in age as being prone to Bell’s palsy . This waA Nigerian study showed the median age of occurrence to be 35.5 years, echoing studies in European settings . A TogolThe narrative on age from these studies, worldwide is that Bell’s palsy is a condition of the young and middle-aged adult with the elderly being in the minority. A Brazilian study of 180 patients with Bell’s palsy however, found two peaks, namely, third- fourth decade and sixth decade of life . Some stThere was a male preponderance on univariate analysis which however, didn’t emerge on using the multivariate analysis in this study. A majority of studies on Bell’s palsy demonstrate no difference in occurrence between the sexes , 17. ThePrevious studies on the relationship between seasons and Bell’s palsy have had varied observations with some finding a clear association or seasonal clustering and yet others not finding any such connection. In a study of a 1000 patients with facial palsies, reporting on seasonal data between 1969 and 1973, no preference of occurrence was found between warm and cold climates . Yet anoPatients seen at our hospital are from a poorer section of Pretoria, a social construct from Apartheid South Africa. The low socioeconomic status would carry stressors unique to this population. A link between psychological stress and the development of Bell’s palsy has been described .To our knowledge, this is the first study to demonstrate HIV infection, younger age and cold seasons as independent predictors of Bell’s palsy among black South Africans. HIV infection is associated with oxidative stress affecting both the central and peripheral nervous systems  –25. The HIV infection has been associated with lower levels of S-adenosylmethionine, the principal methyl donor in cytosine methylation metabolite important for transmethylation which is important for myelin formation . Low levThe extent to which nutrition played a role was not established in this population. Vitamin deficiencies have been described as a common co-existence with HIV infection in poorer communities resulting in neuropathies .There were no cognitive deficits detected in our patients with Bell’s palsy, including the HIV positive group. A literature search on HIV positive Bell’s palsy and cognitive function did not yield results. Future studies with robust assessments for even mild cognitive changes in HIV positive Bell’s palsy individuals could be of value. The high number of individuals in this study not on antiretroviral therapy is concerning. This however, would have improved post September 2016 with the introduction of the “test and treat” policy in South Africa . The effThis study availed an opportunity for an improved understanding of incident Bell’s palsy and its risk factors in the black African patient. Prevention strategies could possibly emanate from improved knowledge of Bell’s palsy, a condition which continues to be regarded as idiopathic. Furthermore, efficacious and cost-effective treatment programmes will emerge from an in-depth understanding of Bell’s palsy. Bell’s palsy is also a possible outcome of psychological stressors linked with a poor socio-economic status prevalent amongst the studied population of black South Africans. Further studies on the latter are needed. Government legislation has since changed in South Africa, with much improvement in availability of ARV treatment.Environmental factors by seasonality, younger age and HIV positivity are important and independent risk factors of Bell’s palsy. Education and awareness programs on the possible effects of HIV and seasons on the development of Bell’s palsy are necessary. A better understanding of this condition and its predictors could lead to well designed preventative measures amongst young black South Africans.


Background: The AR-V7 splice variant is a cause of castration-resistant prostate cancer (CRPC). However, testing for the presence of AR-V7 by real-time polymerase chain reaction (RT-PCR) shows AR-V7 positivity in healthy individuals. We hypothesized that the positivity reflects contamination by hematopoietic cells. We tried a novel circulating tumor cell (CTC) enrichment instrument, using Celsee, to clear hematopoietic cells. Methods: We tested whole blood or Celsee-enriched samples for AR-V7 by RT-PCR, and included samples from 41 CRPC patients undergoing sequential therapy. We evaluated the associations between AR-V7 status and clinical factors. We evaluated factors affecting AR-V7 positivity. Results: AR-V7 positivity was lower in Celsee-enriched than in whole blood specimens. AR-V7 and clinical factors did not predict the therapy effectiveness. We found no significant differences in the effectiveness of enzalutamide/abiraterone (Enz/Abi) upon AR-V7 evaluation. All AR-V7 positive patients had resistance to Enz/Abi. Docetaxel (DTX), cabazitaxel (CBZ), and Radium223 treatment showed no significant difference in the treatment effectiveness, regardless of AR-V7 presence. AR-V7 was more frequently positive than Extent of disease (EOD) 2 in cases with bone metastases. Conclusion: Celsee CTC enrichment suppresses AR-V7 false positivity. All AR-V7 positive patients presented resistance to Enz/Abi. DTX, CBZ, and Radium223 were effective and remain treatment options. AR-V7 positivity should progressively appear in patients with advanced bone metastases. Androgen receptors (ARs) are encoded by eight exons (exons 2–3 are DNA binding domains and exons 4–8 are ligand binding domains (LBDs)). The AR splice variant 7 (AR-V7) has exon 3 followed by a cryptic exon 3 and omits exons 4 to 8. It lacks the LBD but retains functional, transcriptive element binding domains that mediate intracellular AR signaling in a ligand-independent manner ,2.AR-V7 has attracted attention because of its association with castration-resistant prostate cancer (CRPC). Enzalutamide (Enz), an inhibitor of AR signaling that binds to the LBD of the AR ,4, and aCTC analysis is usually performed in two steps (CTC enrichment and detection), but no standardized method exists. Problems during CTC enrichment include the possibility of contamination by hematopoietic cells and missing CTCs. The PCR detection is directly affected by the accuracy of CTC enrichment, and its results may reflect contaminations by cells other than CTCs . For exaGiven the differing sensitivity and specificity of AR-V7 assessment tests, depending on the test system, we considered the following two points to be important when assessing AR-V7 positivity: one was to exclude hematopoietic cells as much as possible during CTC enrichment, the second one was to target AR-V7 mRNA from CTCs during detection.Celsee  is a microfluidic device that can be used for CTC enrichment. Compared with CellSearch, which is the only system approved by the U.S. Food and Drug Administration (FDA), the capture rate of Celsee for CTCs is high . The basWe hypothesized that Celsee CTC enrichment would suppress AR-V7 false positives. The first aim of this study was to confirm the difference in the detection rate of AR-V7 between the PAXgene systems without CTC enrichment and those with Celsee CTC enrichment. We used samples from patients with CRPC treated with sequential therapy.We assumed that analysis of AR-V7 using Celsee would predict the outcome of CRPC treatment, and our second aim was to evaluate the associations between the current treatment efficacy and variables, such as the presence of AR-V7, and prognostic or clinical factors , lactate dehydrogenase (LDH), albumin (Alb), hemoglobin (Hb), metastatic sites on viscera, bone, or lymph nodes, Gleason score (GS), time-to-CRPC (period from the start of hormone therapy to CRPC), time-from-CRPC (period since becoming CRPC), and the history of therapeutic drug use).AR-V7 is thought to be positive during CRPC treatment. Our third aim was to identify factors affecting AR-V7 positivity by examining the association between prognostic and clinical factors.From January 2018 to September 2019, the study included a total of 41 patients with CRPC, including 38 with metastatic CRPCs (mCRPC) and three with non-metastatic CRPC (nmCRPC). All patients were treated with surgical castration, degarelix acetate, leuprorelin acetate, or goserelin acetate as androgen deprivation therapy in the Showa University hospital and received CRPC treatments with Enz, Abi, DTX, CBZ, Radium223, and traditional hormones . We also included samples from eight healthy controls recruited from volunteers without prostate cancer in the Showa University Urological Department. The Showa university clinical research ethics boards approved the study . All patients provided written informed consents.We measured PSA levels and obtained other laboratory tests for monitoring monthly. Imaging such as computed tomography (CT), magnetic resonance imaging (MRI), and bone scintigraphy were performed at least every 3–6 months.We defined stable disease as that in individuals with a <50% PSA decrease to <25% PSA increase from a PSA nadir, and disease response as that in individuals with a PSA decrease >50% in the absence of radiographic progression. We defined disease progression as radiographic progression or PSA increases ≥25% and ≥2 ng/mL above the nadir or baseline. We used Prostate Cancer Clinical Trials Working Group (PCWG) 3 soft tissue and bone scan criteria to assess radiographic progression . Time pog for 5 min at room temperature, we discarded the supernatants and resuspended the isolated cells in 8 mL of 1% Bovine Serum Albumin (BSA)/ Phosphate-Buffered Saline (PBS). We ran the samples through Celsee and collected the cells on the chip in 1 mL × 8 back flushes using 1% BSA/PBS, and centrifuged them at 326× g for 5 min. We used an RNA isolation NucleoSpin kit , according to the manufacturer’s protocol.We placed 5 mL of blood in anticoagulant, ethylene–diamine–tetra–acetic acid (EDTA) blood tubes. We treated 4 mL blood samples with red blood cell (RBC) lysis buffer (10×)  and let them stand for 20 min on ice. Following centrifugation at 326× We collected 2.5 mL blood samples into Paxgene blood tubes and stored them at −80 °C. We thawed the blood samples prior to extracting RNA from them using the Paxgene blood RNA kit , according to the manufacturer’s protocol.We processed all samples after RNA extraction with a DNase kit  and then ethanol-precipitated the DNA-free RNA samples with Ethachinmate .C system to determine RNA concentrations and absorption at 260 and 280 nm. We only used samples with a 260/280 ratios ≥2.0. We performed reverse transcription (RT) with 1 µg of RNA using a high-capacity complementary DNA (cDNA) Reverse Transcription Kit , according to the manufacturer’s protocol.We used the NanoDrop OneWe used the SYBR Green method for our RT-PCR assays. We made cDNA using the KAPA SYBR FAST qPCR Master Mix  to detect prostate cancer-associated RNA transcripts.We adapted the tests for detection of AR-V7 by RT-PCR, using custom primers specific for AR-V7 . We used primers for glyceraldehyde-3-phosphate dehydrogenase (GAPDH)  as a housekeeping gene.We performed RT-PCR under optimized conditions at 95 °C × 30 s, 95 °C × 5 s, and 60 °C × 30 s for 40 cycles, as well as 95 °C × 10 s and 65 °C × 5 s followed by melting curve analysis.We measured product concentrations using the CFX96  instrument and analyzed results with the CFX Maestro software (Bio-Rad). We confirmed that all AR-V7 positive specimens were GAPDH-positive.We collected 4 mL of whole blood samples from eight healthy volunteers into EDTA blood tubes. Subsequently, we performed RNA extraction, RT, and PCR assays on these specimens, and confirmed AR-V7 positivity in six cases .The figure shows the results of PCR tests in AR-V7-positive reactions of five healthy volunteers and Milli-Q water as a negative control (green line). The melting peak of AR-V7 lies around 0.5 degrees of 81.5 degrees.We observed an increase in Threshold Cycle (Ct) value with Milli-Q water, which was used as a negative control, but this probably reflects amplification of primer dimers. We considered AR-V7 positivity only when these conditions applied simultaneously: the melting peak was the same as that for AR-V7, and the Ct value increased.We found a Ct value elevation in the negative control (green line), but the melting peak clearly differed from it. We confirmed AR-V7 positivity in samples from six of eight individuals.We passed 4 mL blood samples from the six healthy volunteers positive for AR-V7 into the whole blood analysis through a Celsee instrument. The RT-PCR results confirmed these samples were negative for AR-V7 .We used Vcap as a positive control (red line) and Milli-Q water as a negative control (green line). The other two lines (blue and brown) are those for the healthy volunteers’ samples.The figure shows that the whole blood of the two healthy volunteers became negative after Celsee enrichment, and the melting peak was detected on the primer dimer side, but not on the AR-V7 graph line. We were able to confirm similar results for all six patients who displayed AR-V7 positivity in their whole blood samples.We spiked 10 and 100 Vcap (ATCC CRL-2876) into 4 mL healthy volunteer blood samples and added Celsee enrichment in the same manner to detect AR-V7 in RT-PCR. We confirmed AR-V7 detection .The red line in We found a melting peak similar to that of AR-V7 in the Vcap (10 and 100) spike group, and confirmed the melting peak only in the primer dimer graph portion in the Vcap 0 spike.By these procedures, we showed that the AR-V7 positivity in the whole blood of healthy volunteers became negative after Celsee enrichment; thereby, we confirmed that tumor-derived AR-V7 can be detected.By these procedures, the AR-V7 positivity in the whole blood samples of healthy volunteers became negative, and we confirmed that tumor-derived AR-V7 cells can be detected.We did not detect AR-V7 after Celsee enrichment in healthy individuals, and thus, we did not set a Ct value threshold for it in this study. We defined AR-V7 positivity as when GAPDH was positive by PCR and the melt peak of AR-V7 was confirmed within 0.5 degrees around 81.5.p < 0.05 as statistically significant.We performed all statistical analyses using the SPSS Software v.21.0 . We applied the Mann–Whitney U test to compare continuous variables , and Fisher’s exact test for categorical variables . We further analyzed factors with a significant difference using a multivariate logistic regression analysis. We considered p = 0.016). □ Hemoglobin (Hb) (SD) was 12.1 g/dl (1.4) for stable disease or response and 10.6 g/dl (1.5) for disease progression (p = 0.005). The time-to-CRPC (SD) was 36.9 months (35.6) for stable disease or response and 16.7 months (13.6) for disease progression (p = 0.005). p = 0.143), Hb , or time-to-CRPC .p = 0.066; We confirmed the effectiveness of Enz and Abi in past and current treatments of patients with or without AR-V7 positivity. We found no statistically significant differences, but none of the AR-V7-positive patients displayed Enz and Abi treatment effectiveness .p = 0.006).Among the patients with bone metastasis, the Celsee AR-V7-positive/negative ratio was 3 (7.3%)/27 (65.9%) in patients with an EOD2 classification or lower, and the Celsee AR-V7 positive/negative ratio was 6 (14.6%)/5 (12.2%) in those with EOD3 or higher (p = 0.058). The difference in the ratio of patients with EOD2 or lower/patients with EOD3 or higher was confirmed .Following our multivariate analysis , we founAR-V7 positivity may vary with the CTC method used to process the samples. False positive results may misguide a patient’s treatment. When interpreting AR-V7 status, the enrichment method used needs to be considered, and AR-V7 should be detected by PCR (reflecting mRNA levels) or by antibody reactions to measure the protein levels.Benign blood cells have been shown to express AR-V7. To further confirm the expression of ARV7, Marín-Aguilera revealed that CD4 and CD8 T-cells, B lymphocytes, T-natural killer cells, and monocytes isolated from PBMC became positive AR-V7 in PCR detection . TakeuchIn the Sciarra review, the mCRPC AR-V7 positive rate was reported at 18.3% (range 17.8–28.8%) , and ourOur AR-V7-positive patients were all resistant to Abi and Enz treatments . Possible causes for the resistance include lineage plasticity and AR indifference, glucocorticoid receptor activation, AR gains or LBD mutations, alternative AR variants and genomic structural rearrangements, AR enhancer amplification, and the presence of additional oncogenic pathways other than AR-V7 . Also, DThe JHU method is known as the AR-V7 PCR detection method after CTC enrichment. CTC enrichment is done with immuno-magnetic beads coated with anti-EpCAM and anti-Her2, and end-product lysates are evaluated on multiplex PCR with AR-V7, AR, PSA, Prostate Specific Membrane Antigen (PSMA), and Epidermal growth factor receptor (EGFR) primers. In the PROPHECY study, Enz and Abi were effective in 6–11% of AR-V7 positive patients [In the Epic Sciences platform, the effectiveness of Enz and Abi were both 0% in AR-V7-positive patients . This plAnother implication of our results is that AR-V7 positive patients have more bone metastases than those with EOD3, and these patients have more CTCs in their blood. A limitation of our system is its inability to assess the CTC counts. Other limitations of our study include the small number of samples studied. We targeted patients undergoing sequential therapy for CRPC and could not assess OS or progression-free survival. However, other reports have shown that AR-V7 negative patients do not usually have AR-V7 re-evaluations, with disease progression after their initial AR-V7 assessment and before the beginning of treatments for CRPC. Nakazawa showed that therapeutic interventions modify the AR-V7 status . StudyinAR-V7 false positives can be suppressed with a Celsee CTC enrichment strategy. All AR-V7-positive patients had resistance to Enz and Abi treatments after Celsee enrichment, and treatment with DTX, CBZ, and Radium223 improved their responses. Our results also showed that some AR-V7-negative patients also presented Enz and Abi resistance, and that AR-V7 is predominantly positive in patients with bone metastases greater than EOD3.


Persons with Disabilities (PWD) experience unmet needs related to health, rehabilitation, education, livelihood, social participation, and empowerment, particularly those living in a resource-poor context such as in the Indian context. The same applies to Children with Disabilities (CWD) as well. Given the pandemic restrictions imposed by the government of India, the provision of therapeutic rehabilitation services for PWDs and CWDs has come to a deadlock. Therefore, the PWDs and the parents of CWDs are substantially impacted by the double contextual burden of demand and access to rehabilitation services in India. However, there has been some light at the end of this dark tunnel provided by the existing telecommunication strategies. Both parents/caregivers and rehabilitation service providers started to find a way out of this situation on their own in India by optimizing their skills and resources for telerehabilitation. However, adopting this strategy requires evidence. Hence a critical Strengths Weaknesses Opportunities and Threats (SWOT) analysis of the telerehabilitation strategy for empowering PWDs and CWDs in an Indian context is warranted and is of immense public health importance. A narrative review was conducted.Telerehabilitation has several strengths, weaknesses, opportunities, and threats. Telecommunication resources, Access to Rehabilitation services, Parent’s and consumer acceptance, Service efficiency, and data documentation could be considered as strengths; Skills, Competencies, Opportunity cost, Resource intensiveness, Evidence for Effectiveness, Comprehensibility could be considered as weaknesses; Therapy innovations, Evidence generation, System strengthening and Capacity Building could be considered as opportunities; Patient Safety, Ethical Integrity, Data security, and Professional practice insecurity could be considered as potential Threats to Telerehabilitation. Telerehabilitation has considerable scope for providing meaningful therapeutic experience and hastens the process of rehabilitation of CWDs in the current context. The SWOT and its implications must be kept in mind to ensure that CWDs receive the best quality continuum of care in the present context with utmost ethical and evidence-based considerations. This could bridge the gaps in access to rehabilitation services with sustainable solutions than patchy temporary solutions that are not sustainable. PWDPersons with DisabilitiesCWDChildren with DisabilitiesGBDGlobal Burden of DiseasesWHOWorld Health OrganisationCOVID-19Corona Virus Disease 2019SWOTStrengths Weaknesses Opportunities and ThreatsLMICsLow and Middle-Income CountriesHICsHigh-Income CountriesPersons with Disabilities (PWD) experience unmet needs related to health, rehabilitation, education, livelihood, social participation, and empowerment, particularly those living in a resource-poor context such as in Indian context . The samHowever, in India, it is believed to be 2.21% of the population . AlthougRehabilitation enables PWDs of all ages to maintain or return to their daily life activities, fulfill meaningful life roles, and maximize their well-being . It is aGiven the situation, developing successful rehabilitation models and their appropriate implementation is of paramount importance to meet the current need for rehabilitation . Variousnd March 2020, India announced ‘Janata Curfew’, urging people to stay home except those in essential services extended till 31st May 2020 in four phases [One must also not forget that this is a pre-COVID context to empower PWDs and especially CWDs in India. The World Health Organisation (WHO) declared the Corona Virus Disease 2019 (COVID-19) outbreak as a pandemic and advised the call for countries to take immediate actions and response to treat, detect and reduce transmission to save people’s lives . Subsequr phases . Given tr phases . Rehabilr phases . TherefoMuch of the information available to the general public regarding the guidelines to be followed during the pandemic was not available in accessible formats . Even ifHowever, there has been some light at the end of this dark tunnel provided by the existing telecommunication strategies. Both parents/caregivers and rehabilitation service providers started to find a way out of this situation on their own in India by optimizing their skills and resources for teleconsultations . The conTele-medicine or health is the use of electronic technologies and telecommunications in the field of health . This coTele-rehabilitation is defined as “the clinical application of consultative, preventative, diagnostic, and therapeutic services via two-way interactive telecommunication technology” . TherefoGiven the pre-pandemic and the present pandemic context for rehabilitation service provision, telerehabilitation could be a feasible strategy to meet the needs of CWDs in an Indian context. It could also potentially hold a way for the post-pandemic future for empowering CWDs in India. However, this strategy has several implications for clinical and public health practice which must be carefully analyzed and understood before embarking on accepting it for implementation in a context like India. Tele-rehabilitation has several strengths for empowering CWDs in an Indian context. The first and foremost strength is the telecommunication resource itself. India has one of the best telecommunications networks available in the developing world with the promised rollout of 5g connectivity in less than a year . In a coTele-rehabilitation could serve the intended purpose of bridging the gaps in access at a considerably lesser cost and thereby enhancing efficiency in service provision . TelecomThe weaknesses for implementing telerehabilitation for CWDs in India is just opposite to its strengths. Though telecommunication resources are surplus, India is still a country with a low literacy rate per million population, and this applies to their health, telecommunication, and technology literacy too . The skiMost parents may not be prepared for rapid changes in technologies. Furthermore, they find themselves lost and confused about their child’s disabilities . The locRemote provision of telerehabilitation services is resource intensive. Resources for telerehabilitation are also prohibitive, which many parents and caregivers of CWDs may not be able to afford . CommuniReflecting on the weaknesses would portray the potential opportunities that telerehabilitation possesses in an Indian context. Firstly, there is a definitive need to develop innovative interventions that suit the needs of CWDs, the context, the available resources, and the systems . These iThere are not many systems in place for the organized provision of rehabilitation services both in the government and private sectors. Therefore, the issue of relevance in addition to rigor becomes vital for a context like the Indian context. This relevance is an opportunity for developing appropriate, organized, and inclusive telerehabilitation systems through new systems or appropriate integration in the existing systems . Though Lastly, but importantly, to initiate any efforts towards all these opportunities will require capacity. Even to assess the adequacy, acceptance, and feasibility of telerehabilitation innovation, all stakeholders’ capacity building is essential. Thus, capacity building of the rehabilitation service providers, service consumers (parents of CWDs), informal caregivers, telecommunication experts, telerehabilitation administrators, and policymakers on specific aspects and their responsibilities is fundamental. Therefore, it is necessary to have an inbuilt curriculum within the health professional education to build the telerehabilitation capacity for the future .Similar to opportunities, there exist few threats too in implementing telerehabilitation in India. A considerable threat that has been spoken about a lot in the recent past has been data theft. Telerehabilitation involves sharing huge volumes of patient information virtually every day. Many clients even make payments online for the services that they may receive. The humongous amount of data generated, utilized, stored, and shared, in day-to-day telerehabilitation practice, may likely be hacked or stolen by hackers and cybercriminals . TherefoEthical integrity could be at threat primarily because of the above two reasons. Lack of trustworthiness in the majority of the existing telerehabilitation platforms, the confidentiality breach, and concern for privacy during the care and rehabilitation of CWDs are a significant threat . Also, tThe “New Normal” way of living in the COVID-19 pandemic has mostly changed people’s lives and livelihood and perspective. However, when it comes to CWDs, even the new normal, is quite different. The “New Normal” has a different “New” and a different “Normal” for CWDs, their parent, and their caregivers particularly in a context like India. The pandemic situation is the only burden for people without disabilities, whereas, for those PWDs and CWDs, it adds to the pre-pandemic burden. The current time may be the ideal time to implement telerehabilitation, considering the “New Normal” way of living.Telerehabilitation, similar to any other intervention strategies has its strengths, weaknesses, opportunities, and threats. The key consideration in its implementation, however, is reliant on the “context”. The individual, social, cultural, political, and policy situation in a specific country. The understanding of the health professionals and rehabilitation experts about teamwork in the rehabilitation of CWDs, particularly in India is limited since rehabilitation is generally uni-disciplinary, specialist-driven, and available only in urban regions for those who can afford it. The opportunities provided by the “New Normal” paves the way for the much-needed changes in the rehabilitation care delivery both by the rehabilitation providers and the recipients. Currently, the application of telecommunication technology for sustainable development is growing at a significant pace; however, their use in health and rehabilitation is not to that extent. Although very limited, there exist systems in the country funded by the state, private sector, and civil societies to promote the provision of rehabilitation services for CWDs and empower them inclusively. These are considered necessary in High-Income Countries (HICs), and there is a considerable investment in the above aspects in HICs. However, the context overall is very different not just in India but in many LMICs.Telecommunication technology is compelling in terms of creating an impact if optimized systematically. Experts in the field of rehabilitation must innovate safe, efficient, and effective interventions using telecommunication technology systematically . By beinLastly, CWDs must never be forgotten in technological innovations and the systematic interdisciplinary efforts for telerehabilitation. Two key aspects to keep in mind when innovating and implementing telerehabilitation services are 1. Early and Intensive multi-disciplinary therapeutic simulation could help hasten prognosis and enable them to become independent and empowered. 2. Each child is very different, and therefore the one size fits all kind of intervention does not work when telerehabilitation innovations for children with disabilities are envisaged. This becomes even more challenging for telerehabilitation service providers when impairments and disabilities are severe. A strategic solution to address these key aspects is to firmly adhere to the ethical principles for professional telerehabilitation practice. Telerehabilitation must not harm or outweigh the benefits with its risks and be the source of therapeutic hazards while CWDs receive it. Everyone involved in the provision of telerehabilitation, including parents and caregivers, must hold responsibility for the provision of telerehabilitation services to CWDs.Overall, telerehabilitation has considerable scope for providing meaningful therapeutic experience and hasten the process of rehabilitation of CWDs in the current context. The SWOT and its implications must be kept in mind to ensure that CWDs receive the best quality continuum of care in the present context with utmost ethical and evidence-based considerations. This could bridge the gaps in access to rehabilitation services with sustainable solutions than patchy temporary solutions that are not sustainable.


Equitable access to cardiological rehabilitation services is one of the important elements in the effectiveness of the treatment of cardiovascular diseases as cardiological rehabilitation is an important part of circulatory system disease prevention and treatment. However, in many countries among others, Poland suffers from the underutilization of cardiac rehabilitation services. Cardiovascular diseases are the worldwide number one cause of mortality, morbidity, and disability and are responsible for the substantial increase in health care costs. Thus, the aim of the research was the analysis of geographical accessibility to cardiac rehabilitation services in Poland. Perkal’s method was employed in this research. The conducted research allowed to recognize the regional variation, but also made it possible to classify Polish voivodeships in terms of the level of availability achieved. This enables the identification of voivodeships that provide a good, or even very good, access to cardiology rehabilitation services and those characterized by low, or very low access. It was found that there was a slight regional variability in the access to cardiological rehabilitation services. However, the sufficient development of a rehabilitation infrastructure has been also recognized. Cardiovascular diseases (CVD) are the most-prevalent noncommunicable diseases and the number one cause of mortality, morbidity, and disability, therefore it substantially increases health care costs ,2. In thThe problem is that deaths due to CAD in the European Union accounted for 18% of one million deaths that could be avoided thanks to effective public health, and 32% of 570,000 preventable deaths thanks to timely and effective treatment and secondary prevention . Among tCardiological rehabilitation is eloquently defined by the World Health Organization as “the coordinated sum of activities required to influence favorably the underlying cause of cardiovascular diseases as well as to provide the best possible physical, mental and social conditions, so that the patients may, by their own efforts, preserve, or resume optimal functioning in their community and through improved health behavior, slow, or reverse progression of disease” . IntegraAccording to The European Society of Cardiology (ESC), The Polish Cardiac Society (PTK), The American Heart Association (AHA), The American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR), and the Agency for Health Care Policy and Research, a comprehensive cardiac rehabilitation program should contain specific core components in order to be efficient and successful. One of them is the equity in the access to a cardiac rehabilitation program.Equity matters as it applies to fair opportunity for everyone to achieve their full health potential regardless of demographic, social, economic, or geographic status. Thus, any inequities in access to healthcare services may lead to a low level of population health . RegardiThe core purpose related to the research on the equity in the access to healthcare, is to identify regions where the provision of healthcare services should be higher, and regions that do not require such a high access to health benefits ,45.In this research, we focused on Poland as cardiovascular diseases has been one of the main causes of death in the Polish population for years , while aIn Poland, a comprehensive care program after acute myocardial infarction (named in Polish “KOS-zawał”) has been in operation since 2017. The number of centers implementing the program was constantly growing and in December 2019, services were provided by 60 healthcare providers. In 2019, benefits under the program were granted to 19.6 thousand patients and the value of reimbursement of benefits amounted to PLN (the Polish currency-zloty) 197 million. Out of 9.4 thousand patients who received the above program in 2018, 76% had cardiac rehabilitation, which was 5.2 thousand. A total of 74% of patients undergoing cardiac rehabilitation started rehabilitation within 14 days from the date of discharge from the hospital due to a heart attack. Although there was a decline in the value of cost reimbursement made by the National Health Funds due to CAD, it was nearly PLN 2 billion in 2019 and was lower by PLN 529 million (21%) than in 2014, however the decrease in the cost of reimbursement was observed mainly in the case of services provided for unstable angina (a type ACS) and in the case of chronic CAD . While in the case of myocardial infarctions, the value of reimbursement made by the National Health Funds increased by PLN 50 million (6%) and also in terms of the reimbursement value, hospital treatment dominated (93% in 2019). This is the result of the increase in the number of myocardial infarctions by 9% from 2014 to 2019 mainly due to the demographic structure of patients. Therefore, it is important to ensure equity in the access to cardiac rehabilitation in Poland [Moreover, equal access to health services is one of the priorities of Polish health policy  and an iThus, the aim of the study was to assess the regional accessibility to cardiology rehabilitation centers in Poland. We assumed that potential  access to the health benefits, which is the result of the allocation of resources, was reflected in the usage of CR services, which is the outcome of the healthcare system. We formulated the following hypotheses that cardiology rehabilitation centers are distributed unequally among regions. To the best knowledge of the authors, this is the first research on the accessibility of cardiology rehabilitation in Poland across such a broad range with such methodology ,51,52,53Data related to the number of cardiological rehabilitation centers in Poland in 2019 were derived from the Polish National Health Fund databases ,55. CentThe number of acute coronary syndromes (ACS) in Poland in 2019 was also acquired from the Polish National Health Fund databases. The ACS group consisted of the following ICD-10  classes: I20.0, I20.1, I21, I22, I23, and I24.0. The number of ACS broken down into 16 Polish districts are presented in k is Perkal’s indicator for “k” voivodeship; n is the number of variables; and Zik is the normalized value of the “i” variable for “k” voivodeship.In order to compare access to cardiac rehabilitation in each of the voivodeships, Perkal’s indicator was engaged. Perkal’s indicator is based on data aggregation using normalized variables. The general formula of Perkal’s indicator is given below ,57.Wk =Analyzed variables were divided into two classes. The first class, called “stimulants”, consisted of variables where an increasing value is associated with better access to rehabilitation. In our research, the class of “stimulants” consisted of two variables: the number of inpatient rehabilitation centers and the number of outpatient rehabilitation centers. The second class of variables  included variables that had a negative impact on access to cardiological rehabilitation. In this paper, one variable (the number of ACS) was classified as a “de-stimulant” due to the negative correlation between the number of patients in the early period after ACS and accessibility to rehabilitation.ik is the normalized value of the “i” variable for the “k” district; Xik is the raw value of the “i” variable for the “k” district; Xi mean is the mean value of the “i” variable for all districts; and Si is the standard deviation of the “i” variable for all districts.Before aggregation variables need to be normalized, the process of normalization changes the raw variables to values without specific units of measurement that allows them to be aggregated together. Normalization formulas are different in the case of “stimulants” and “de-stimulants” due to their opposite impact on the assessed phenomenon. Normalization of variables belonging to the class of “stimulants” was calculated using the following formula :Zik =  aggregated two “stimulant” variables: the number of inpatient cardiology rehabilitation centers per 100,000 population  and the number of outpatient cardiology rehabilitation centers per 100,000 population . These variables were classified as “stimulants” because the increasing number of rehabilitation centers correlated with easier access to them. Perkal’s indicator WA was calculated using the given formula below:Ak is the value of the WA indicator for the “k” district; Z1k is the normalized value of the number of inpatient cardiology rehabilitation centers per 100,000 population in the “k” district; and Z2k is the normalized value of the number of outpatient cardiology rehabilitation centers per 100,000 population in the “k” district.In our paper, two types of Perkal’s indicators were used. The first type of the indicator , except the above-mentioned two “stimulants”, consisted of one “de-stimulant” variable: the number of ACS per 100,000 population . This variable was involved in the WB indicator in order to estimate the differences among Polish districts in demand for cardiological rehabilitation after ACS. This variable was treated as a “de-stimulant” because the increasing number of ACS leads to higher demand for cardiological rehabilitation and under the assumption of the constant number of rehabilitation centers, to limitations in accessibility to rehabilitation. Perkal’s indicator WB was calculated using the given formula below:Bk is the value of the WB indicator for the “k” district; Z1k is the normalized value of the number of inpatient cardiology rehabilitation centers per 100,000 population in the “k” district; Z2k is the normalized value of the number of outpatient cardiology rehabilitation centers per 100,000 population in the “k” district; and Z3k is the normalized value of the number of ACS per 100,000 population in the “k” district.The second type of Perkal’s indicator used in this paper .The range of values defining each of the three qualitative classes was different in the case of the W1, X2, X3) per 100,000 population and basic descriptive statistics  are presented in Results of the calculation of variables  and their division into three qualitative classes  are presented in A indicator consisted of two variables: the number of inpatient cardiology rehabilitation centers and the number of outpatient cardiology rehabilitation centers were from −1.193  to 0.995 (the best rehabilitation facilities in Lubelskie voivodeship). The standard deviation of the WA indicator was 0.592, which means a high level of differences among districts.Values of both types of Perkal’s indicators  was between −1.121 for Lubuskie and 0.834 for the Pomeranian voivodeships . The WB indicator was below average for two voivodeships: Greater Poland and Lubuskie (the new one among districts where the access to rehabilitation could be described as lower than sufficient). The remaining eleven voivodeships reached the average value of the WB indicator, which could mean sufficient accessibility to cardiology rehabilitation after ACS. B indicator value in increasing order.The value of the Whips see . The staA in this paper, was composed of two “stimulants” describing the rehabilitation infrastructure (numbers of indoor and outdoor rehabilitation centers in each Polish voivodeships). To enable comparisons among voivodeships, “stimulants” were expressed per 100,000 population.Cardiological rehabilitation is an important part of circulatory system disease prevention and treatment ,60. TherA indicator allowed us to evaluate the differences in the equipment of Polish voivodeships with rehabilitation infrastructure. However, it disregards the demand for cardiology rehabilitation at the level of districts. The second type of Perkal’s indicator , except for two of the above-mentioned “stimulants”, consisted of the “de-stimulant” variable: the number of ACS per 100,000 population. This variable could be perceived as an estimator of demand for rehabilitation after ACS. The use of “de-stimulants” in the construction of Perkal’s indicator has been previously applied by other authors [The W authors ,62.A and WB. The first of them reflects the potential ability of the healthcare system to provide rehabilitation services for patients in the early period after ACS. However, access to cardiological rehabilitation depends not only on the supply guaranteed by existing rehabilitation centers, but also by the demand created by the number of cases of ACS. The WA indicator securely evaluates the supply side of the rehabilitation process because it aggregates data on two different ways of rehabilitation: inpatient and outpatient. Assessment of demand by WA is nevertheless rather weak, as the only one estimator of demand employed here was the size of the population of each voivodeship . It could be efficient approach only in the case of similar incidence of ACS among all voivodeships . Better evaluation of cardiological rehabilitation provides the WB indicator. This indicator contains a good estimator of demand: the number of ACS that allows assess not only to rehabilitation infrastructure, but also the real accessibility to rehabilitation services with regard to the need for rehabilitation after ACS.There is an essential difference in relevance between indicators WA and WB indicators was visible in the results of our investigations. Although the vast majority of examined Polish voivodeships reached at least an average value of Perkal’s indicators (both WA and WB) that could identify sufficient development of a rehabilitation infrastructure, there were differences between the rankings of voivodeships with respect to the WA and WB values. Voivodeships better equipped with rehabilitation centers were favored in the WA indicator ranking, while in the WB ranking, there was awarded accessibility to existing rehabilitation centers taking into account not only the number of them, but also the patients’ needs expressed as ACS incidence. In light of this, the WA indicator can be perceived as a measure of nominal capability of rehabilitation infrastructure, while the WB indicator as a measure of the real availability of cardiological rehabilitation after ACS. A negative health variable as a de-stimulant in a design for an aggregated synthetic indicator has been used in earlier research [The distinct relevance of Wresearch .B indicator was lower than in the case of the WA. This is not only an evidence of lower differentiation of the WB value than WA, but could also indicate a better match of the rehabilitation infrastructure with the real needs defined by ACS incidence than with only the population size of the voivodeships.Additionally, the standard deviation of the WFurther research with the usage of more data on the number of workers in the rehabilitation centers is reasonable in order to precisely identify the efficiency within the cardiological rehabilitation infrastructure. However, it would require more detailed databases regarding the staff of cardiology rehabilitation centers. This implies that policy makers should create a more detailed database. The obtained results are in line with the world research on the recognized barriers of geographic nature to access to CR .As the voivodeships in Poland differ in their accessibility to cardiology rehabilitation centers, this means that some voivodeships were not implementing effective health policies, which would lead to improved access to cardiological rehabilitation services for people in their area. The analysis is particularly relevant for decision-makers and the results of this research should be taken into account in the process of regional planning and by healthcare sector decision-makers. It is of special importance as the proper establishment and development of CR services is essential for the most effective management of heart conditions, otherwise it would have a negative impact on the outcomes of implemented cardiological programs in Poland. Thus, the results presented in this article are important to continue the advancement of knowledge on the subject of equity in healthcare resource distribution and its impact on health.On the basis of Perkal’s synthetic indicator, the accessibility to cardiology rehabilitation after acute coronary syndromes (ACS) in Poland was assessed. This is of high importance as cardiological rehabilitation is an important part of circulatory system disease prevention and treatment.In this research, two types of this synthetic indicator were employed. The first one enabled us to evaluate differences in the equipment of Polish voivodeships with rehabilitation infrastructure. The second type of Perkal’s indicator allowed us to estimate the real availability of cardiological rehabilitation, considering the demand for rehabilitation after ACS, as access to rehabilitation depends not only on supply guaranteed by existing rehabilitation centers, but also by the needs created by the number of cases of ACS. The results showed that most voivodeships were sufficiently developed in terms of their rehabilitation infrastructure, however, there were some that suffered from a lower level of infrastructure. However, through a comparison of both Perkal’s indicators, we found a better match between the rehabilitation infrastructure and the real needs defined by ACS incidence than with only the population size of the voivodeships.Hence, this study can be used as a basis for healthcare policy formulation in order to correct some inequalities of cardiological rehabilitation infrastructure. By having such information, the national government could monitor the nationwide distribution of cardiological rehabilitation infrastructure and provide some advice to regional policy makers  in order to make proper adjustments to the real demand for such services.


The use of videogames and motion capture systems in rehabilitation contributes to the recovery of the patient. This systematic review aimed to explore the works related to these technologies. The PRISMA method  was used to search the databases Scopus, PubMed, IEEE Xplore, and Web of Science, taking into consideration four aspects: physical rehabilitation, the use of videogames, motion capture technologies, and upper limb rehabilitation. The literature selection was limited to open access works published between 2015 and 2020, obtaining 19 articles that met the inclusion criteria. The works reported the use of inertial measurement units (37%), a Kinect sensor (48%), and other technologies (15%). It was identified that 26% used commercial products, while 74% were developed independently. Another finding was that 47% of the works focus on post-stroke motor recovery. Finally, diverse studies sought to support physical rehabilitation using motion capture systems incorporating inertial units, which offer precision and accessibility at a low cost. There is a clear need to continue generating proposals that confront the challenges of rehabilitation with technologies which offer precision and healthcare coverage, and which, additionally, integrate elements that foster the patient’s motivation and participation. One of the sustainable development objectives suggested by the United Nations (UN) is oriented toward the universal and integral coverage of health services, and the reduction of its inequalities, in order for everyone to be in good health . In accoOf the different types of disabilities, motor disability is considered to be one of the main limitations to human beings carrying out their basic activities, affecting the quality of life of the individual, as well as that of those around them . In the Although in the last few years there have been many technological proposals that support physical rehabilitation, there are still difficulties and gaps in the area which represent an opportunity to contribute to improvements in biomechanical data capture accuracy, the coverage and affordability of health services, and the flexibility and motivation offered to the patients.With the purpose of identifying the advances and the options available, in order to contribute to the improvement of motor rehabilitation processes, this review includes works published between 2015 and June 2020, oriented toward the support of upper limb physical rehabilitation, which use videogames and a motion capture system. These publications mainly show the use of the Kinect sensor and inertial sensors as motion capture systems. At the same time, it is identified that the works included mainly support motor rehabilitation in people who have suffered a stroke, and another aspect that stands out is the use of commercial systems on the market, which offer different videogames for motor rehabilitation. The objective of this systematic review is to determine the main contributions to this type of rehabilitation in order to identify the opportunities and challenges that should be taken into consideration in future proposals, focused on the improvement in quality of life of people with motor disabilities.This section provides a description of the process and criteria taken into account to conduct the article selection included in this documental research, according to aspects of the PRISMA method  . This alThe eligibility criteria taken into consideration for inclusion of the studies in this review were (i) that they were published in English, (ii) that they were published within the last 5 years, in the period 2015–June 2020, (iii) that the full text was open access, and (iv) that the type of document was an article, systematic review, state-of-the-art review, or journal.Concerning the second aspect, the period mentioned was selected, given that as, from 2010, when Kinect was created, and until 2015, its use became popular in different contexts. After 2015, it is noticeable that there was an upsurge of companies and projects using other motion capture systems and integrating serious videogames, in addition to the Kinect sensor, in the field of rehabilitation, which is the main interest of the present study. Another relevant element in this review is that the studies included had therapeutic purposes of rehabilitation or telerehabilitation of the upper limb using videogames and some motion capture system, regardless of the gender and age of the population which participated in the validation of the proposals described.The search of the publications was carried out in four academic databases: Scopus, PubMed, IEEE Xplore, and Web of Science. The following search terms, classified into four groups, were used: (i) medical aspect: rehabilitation, health, “physical therapy”, musculoskeletal, telerehabilitation, “tele-rehabilitation”, “tele rehabilitation”; (ii) use of videogames: videogames, “video games”, video-games, “serious videogames”, “serious games”, “serious video games”, exergames, exergaming, “active videogames”; (iii) motion capture system technology: “inertial sensor”, “motion capture”, mocap, “motion capture system”, wearable; iv) segment or part of the body the rehabilitation is focused on: “upper limb”, elbow, shoulder, arm, wrist, humerus. In the search parameters used in the databases see , in eachThe terminology used to refer to motion capture technology often changes between scientific domains. For instance, in clinical studies, it may be possible that focus was given to the manufacturer name. In other papers, alternative terms may have been used, such as simply “accelerometers” or “motion sensing”. We recognize this is a limitation of the methodology adopted in this paper, which may have prevented some papers from being listed in the first stage.The selection process of the works related to the review topic included four phases: firstly, the identification of the studies, in which all the records that respond to the search parameters in each database were taken into account; secondly, the application of a filter, using the eligibility criteria, in order to select the works related to the purpose of the review, which are available and can be accessed; thirdly, a “screening” phase, which filtered out works, eliminating those that did not adjust to the focus of the investigation and/or those which appeared in multiple databases; finally, an inclusion phase, allowing for the identification of documents to be part of the detailed analysis of the systematic review.This section shows the findings of the selection process of the study, as well as the characteristics of the works included in the analysis and the individual results presented in those publications.The main characteristics of the 19 works included in the review could be classified into four groups: (i) according to the motion capture system used; (ii) according to the diagnoses or clinical condition the investigation focuses on; (iii) population included in the validation process; (iv) availability (affordability) of the technology used  in the investigation.Regarding the motion capture systems reported to be used in the 19 studies, nine (48%) used Microsoft Kinect, seven (37%) used inertial measurement units (IMUs), one (5%) used a passive orthosis , one (5%) of the studies used Microsoft HoloLens, and the remaining 5% corresponded to a study which reported a systematic review in a period different from that established and, therefore, it was not considered in the review see .In the studies analyzed, it was identified that 47% of the investigations focused on the treatment of people who suffered a stroke, 11% addressed situations related to the range of movement (ROM), another 11% contributed to the treatment of any injury in the upper limb, 5% oriented their investigation toward people with Friedreich’s ataxia, 5% focused on the treatment of children with cerebral palsy, 5% analyzed energy expenditure in the execution of physical activity, and 16% did not focus on an illness or clinical condition in particular, but on the analysis of technology; thus, they were classified as “not applicable” (N/A), as observed in In the validation process , 47% of With regard to technology availability and affordability, 21% of the works included in this review used commercial products focused on physical rehabilitation. Another 21% proposed systems, referring to the development of technology in academic and/or investigative environments. Most of the studies (58%) were classified as “mixed”, given that the technology used involved a combination of commercial products and some personalized development (mainly videogames), as observed in An additional aspect in the global analysis of the literature is that, although, within the search parameters, the upper limbs were included, it was identified that there was diversity regarding the part of the body being focused on in the works, as presented in The terms rehabilitation and habilitation, according to the World Health Organization , are twoFor the autonomous development of different basic activities, the movement of various parts of the body is required, especially the upper limbs, which allow the realization of diverse complex manual activities . In thisMotion capture (MOCAP) is the process of acquiring motion by combining software and hardware  and is uOptical systems that use infrared light require the location of markers at specific points on the individual’s body. Then, using a configuration with multiple cameras, properly placed around the capture space, the position of the reflective markers is recorded .The measurement of human movement with optoelectronic systems offers precision due to the position of the retroreflective markers, and that depends, to a great extent, on the optical characteristics of the camera system and the algorithms implemented in the monitoring software . MicrosoIn this review, most of the works described how they involved a Kinect sensor as an optical system for motion capture in the development of the research. Some used the sensor, and, in addition, they proposed new products to support rehabilitation. For example,  evaluateFurthermore,  determinOther investigations did not focus on the development of new products, but rather on the validation of different attributes in the use of technologies in motor rehabilitation. In , the autIn the same way, in , the feaAnother approach identified in the works was that of proposals to optimize the data capture by the Kinect sensor. For example, in , a methoWith regard to the use of optical systems, in addition to Kinect, the use of a glove called the 5DT Data Glove Ultra from the company 5DT  was presOn the other hand, in , the potNon-optical systems are based on small inertial sensors with built-in accelerometers, gyroscopes, and magnetometers, which allow the recording of data associated with movement in an integrated storage device; these systems are characterized by their low cost, accuracy, and ease of use in ambulatory environments . PortablDifferent works implemented IMUs due to their potential, such as the case presented in , in whicUnderstanding the advantages of the use of inertial sensors, some works focused on an improvement in their efficiency and, taking into account that one of the limitations that IMUs have shown is the problem of drift, in , a driftAnother aspect of the research was the accuracy offered by IMUs, which is why they were compared with systems recognized as gold standards in motion analysis ,43,44,45Furthermore,  took advOther works used commercial systems involving IMUs, which presented stability in their operation and offerred reliability in the data they provide, allowing the evaluation of their contribution to rehabilitation processes. On the one hand, Bimeo is a sensor-based rehabilitation device aimed at stroke patients and other neurological patients. This device offers a motivating virtual reality environment, which aims to make the therapy effective and motivating for patients and also offers therapists a support tool to monitor and control the Bimeo process . This syThe ArmeoSenso system  involvesThe Myo bracelet, developed by Thalmic laboratories, is a portable movement and gesture control device. The newest version of the system, which consists of eight EMG sensors and IMUs, allows the user to control events from a computer (or other device) via a Bluetooth connection, which has been widely used in research environments because of its accessibility . The MyoAnother aspect of interest in this review was to identify how the use of videogames is being addressed in upper limb physical rehabilitation. It was found that, although some studies involved the use of commercial products, most of them developed new videogames adapted to the needs of the target population of the investigation.In , the comIn , the JRSFurthermore, works were identified in which, regardless of whether the motion capture system was commercial or an independent proposal, specific videogames for the development of the investigation were presented. In this group of works, the development of videogames that used the platform Unity was noticeable . For exaUsing Unity 3D and the C# programming language,  developeIn one of the cases in , a rehabThe use of Kinect and its utilities was also noticeable in , throughIn , a serioUsing C# and Microsoft XNA game studio, in , a game Another example of videogame development for physical rehabilitation was included in the SCRIPT system , designeAnother approach to the use of developed videogames, specifically for motor recovery, was the comparison of competitive, cooperative, or individual videogames. In this regard,  designedThe publications analyzed in this review were oriented toward the support of physical rehabilitation using technology. Most of these works fostered the recovery of patients who suffered from a particular clinical condition. Below, there is a description of the contribution made by each of them.A cerebrovascular accident, also known as a stroke, is an acute event, caused primarily by a blockage , which prevents blood from flowing to the brain. They can also be caused by bleeding from a blood vessel in the brain or by blood clots . One of In the review, it was identified that most of the works were geared toward the support of motor rehabilitation treatments in post-stroke patients, as is the case of ,21,22,25Another diagnosis mentioned was cerebral palsy, which is the most frequent cause of motor disability in children and the third cause of disorders in neurological development. It is, in essence, a group of nonprogressive disorders which occur during the development of the brain, in the fetal phase or the first years of life. These disorders affect mobility and postural development; therefore, they also make carrying out different activities more difficult . In 7],,7], the Additionally, in , the conAnother aspect of interest related to human health is that of energy expenditure in the execution of physical activity, given that energy expenditure and the metabolism substrate are important elements when considering physical activity, and, from their characteristics, it is possible to establish treatments to improve a person’s quality of life . Hence, Concerning the evaluation and analysis of the range of movement, and the lesions in the upper limbs derived from different clinical conditions, in ,9,12,16,In conclusion, the findings of the analysis of the articles which met the inclusion criteria of the review can be classified as is shown in the Venn diagram in It is necessary to mention that, while optical motion capture systems (11 papers) presented problems with sensor occlusion, in the systems using IMUs or non-optical systems (eight papers), the investigations were left open in order for future research to obtain better precision and to correct the drift generated by the magnetometer. In addition, for the years 2019 and 2020, the literature consulted registered an increase in the use of non-optical motion caption systems (five papers), as opposed to optical systems (two papers).Furthermore, regarding the use of videogames in physical rehabilitation, there was a clear trend toward the development of personalized videogames (13 papers) and, on fewer occasions, commercial videogames were used (six papers).Taking into account that the objective of the investigation included the integration of motion capture systems and videogames in upper limb physical rehabilitation, it is appropriate to mention that future investigations could focus on the development of technological tools involving IMUs and the independent development of videogames for the support of said processes.According to the importance of physical and functional rehabilitation in the quality of life of patients and the people around them, in this review, the technological contributions developed in the past few years in this field were identified, mainly regarding the inclusion of videogames and motion capture systems as support in the motor recovery of the upper limb. In the literature, a wide use of Kinect was identified as the motion capture system, although there were some limits regarding the movements carried out in the depth and occlusal planes of the limbs, i.e., the visual interruption between the camera and some of the body segments, as well as the capture of data in some specific positions . Furthermore, aspects related to precision were considered in ,60,61, wIn this sense, comparisons were made of different motion capture systems with respect to Vicon, OptiTrack, or Qualisys considered to be the gold standard, against which those systems using inertial measurement units have shown a comparable performance ,44,45,62Currently, novel motion capture technology involving video alone is available. Using tools from machine learning, researchers have demonstrated that tracking joints of multiple human figures may be achieved . The potOn the other hand, the use of serious videogames has increased due to the lack of motivation of patients when they are in the process of motor recovery. In the face of this, individual, cooperative, and competitive video games have been used. Commercial video games were used in ,19,20,21When referring to the use of commercial products, i.e., videogames and motion capture systems, it should be noted that they are an important contribution to the field of rehabilitation. However, they are not certified as medical products  and, theAlthough this review included works that used videogames and motion capture systems in physical rehabilitation, not all the works analyzed integrate these components into a single product or system, i.e., the information generated by these technologies was disconnected, making complete and timely analysis difficult in motor recovery therapy.One of the fundamental aspects in order to achieve the objectives of a physical rehabilitation process is that it is adequately monitored and controlled, and that it is adjustable in a timely manner regardless of whether the patient and the health professional are in the same geographical location or not. For this reason, an optimal system to support physical rehabilitation should integrate various functionalities and technologies, including an accurate and portable motion capture system, as well as a customized active video game module to encourage patient motivation and guide them properly in the execution of therapy. It is also important that the system has a management and monitoring module of the rehabilitation plan assigned to each patient in real time, making it possible to manage the electronic medical record of rehabilitation processes.In this sense, out of the works included in this review only five presented home rehabilitation systems that allow the therapist to remotely adjust and monitor the configuration of the game according to the patient’s rehabilitation objectives, incorporating the recording of information in an associated computer system. Out of these, in , IMUs arThe ability to carry out basic daily activities autonomously is an aspect related to an individual’s quality of life. People can lose their mobility and their capacity to execute daily activities for different reasons, as in the case of neurologic diseases or other clinical conditions. In order to recover functionality, physical rehabilitation systems are implemented that require, in addition to knowledge and orientation from professionals in the area, tools and technologies which provide precision and optimize the process. Motivation and commitment of the patient are also required, as reported in the works analyzed in this research.This review included studies which support the physical rehabilitation of the upper limb with the use of videogames and motion capture systems, and it identified 19 documents which met the criteria of eligibility defined for this investigation. In the documents analyzed, it was found that, concerning motion capture systems, the use of Microsoft Kinect is prominent, due to its affordability and ease of use. There was also a strong trend regarding the implementation of IMUs given their precision and portability.Concerning the affordability of the technologies used, it can be stated that most of the works used commercial systems and complemented them with the development of components allowing the adjustment of the technology to rehabilitation processes. Development mainly involved personalized and configurable videogames that respond to some requirements of the motor rehabilitation process, especially attending to the need to foment, increase, and maintain the motivation of the patient in the execution of the therapy. In general, the works showed the advantages provided by the use of active videogames in the recovery of patients, as long as they are designed and developed with the accompaniment of physical and functional rehabilitation professionals, and that they can be used in the patient’s environment.The studies analyzed included videogames, as well as motion capture systems, although only 26% of these works integrated the different components into one sole product and complemented them with a system that manages the data of the patients for respective monitoring throughout therapy. Thus, in general, this review identified that an optimal system to support physical rehabilitation should include a motion capture system that offers precision and portability, a module of active videogames that are configurable to the particular needs of each patient’s recovery, which permit motivation and proper guidance in the execution of the therapies and, lastly, a computer system which allows the management and monitoring of the rehabilitation plan assigned to each patient, attending to the fundamental aspects of telerehabilitation.