Mirror visual feedback as therapeutic modality in unilateral upper extremity complex regional pain syndrome type I: randomized controlled trial.

BACKGROUND: There is growing evidence for the effectiveness of mirror therapy (MT) on pain reduction in patients with type I complex regional pain syndrome (CRPS I). AIM: To evaluate the efficacy of MT on pain reduction and hand function in subjects with unilateral upper extremity CRPS I. DESIGN: Randomized controlled trial with control group cross-over (half cross-over design). SETTING: Subjects with CRPS I were outpatients of a university hospital and cooperating centers. All patients carried out the daily exercise at home. POPULATION: Subjects with unilateral upper extremity CRPS I meeting the Budapest diagnostic criteria. METHODS: Subjects were randomly divided into two groups. Group A (N.=13) carried out a ten-minute MT exercise daily, for a total duration of six weeks. Group B (N.=14) acted as a control group for six weeks followed by six weeks of MT with the same characteristics as Group A. Upper extremity active range of motion, strength, dexterity, limb volume, affected-to-unaffected hand temperature difference, and health-related quality of life were evaluated before and after each period. Daily records on the visual analogue scale were used for pain evaluation. Effectiveness was calculated using mixed-effects modelling for between-group comparisons and within-group variability, and identification of significant predictors. RESULTS: Twenty-three females and four males with an average age of 56.1±9.6 years completed the study. Except for the affected-to-unaffected hand temperature difference, both groups consistently demonstrated significant or near-significant improvements in measured parameters after MT period. The improvements were evident upon an intergroup comparison of Group A and the control period of Group B as well as longitudinally within Group B. No significant improvement was found during the control period. CONCLUSIONS: Principles focused on mirror visual feedback to the central nervous system can sustain promising therapeutic potential as part of the treatment for pain reduction and hand function in CRPS I patients. CLINICAL REHABILITATION IMPACT: MT can be considered as part of the therapeutic regimen employed for the treatment of CRPS I.

COVID-19 reduces cardiorespiratory fitness even months after a mild to moderate acute phase: a retrospective cohort study.

BACKGROUND: COVID-19 survivors may experience long-term health problems, including deterioration of cardiorespiratory fitness (CRF), as demonstrated by several cross-sectional studies that compared the results of cardiopulmonary exercise tests (CPET) performed only after COVID-19 with predicted values. This study aimed to analyze a change in CRF between repeated CPETs in response to suffered COVID-19. METHODS: A total of 127 healthcare workers (HCWs; mean age 55.7 years) underwent two CPETs with a mean interval of 762 days. Forty HCWs suffered from COVID-19 (mild to moderate severity) in the interim (321 days before the second CPET), and 87 HCWs formed a control group. Mixed-effects regression with multiple adjustment and interaction terms was used for two response variables - maximum oxygen uptake (VO2 max) and power output. RESULTS: Between both CPETs, mean VO2 max decreased statistically significantly in the COVID-19 subgroup (by 3.12 mL/kg/min, p = .034) and insignificantly in controls (by 0.56 mL/kg/min, p = .412). The proportion of HCWs achieving predicted VO2 max decreased from 75.9% to 59.5% (p = .161) in COVID-19 survivors, while it increased from 73.8% to 81% (p = .274) in controls. COVID-19 (ß = -0.66, p = .014) and body mass index (ß = -0.49, p < .001) were independent negative predictors of VO2 max change. COVID-19 was not associated with a change in power output. CONCLUSIONS: On the basis of repeated CPETs, COVID-19 significantly, albeit rather modestly, reduces CRF almost one year after infection. The reduction persists even after the acute phase with mild or moderate severity.

Predictors and characteristics of post-acute COVID-19 syndrome in healthcare workers.

BACKGROUND: Post-acute COVID-19 syndrome (PCS) is a multisystem disorder degrading the quality of life. The study determined characteristics and predictors of PCS in unvaccinated healthcare workers (HCWs) suffering from PCS based on a comparison with their fully recovered counterparts. METHODS: 305 HCWs were examined at least 12 weeks post COVID-19 symptom onset to obtain data about their acute phase of COVID-19 and current health status and tested for complete blood count, C-reactive protein (CRP), electrophoresis of plasma proteins and SARS-CoV-2-specific immunoglobulin (Ig) G and M. RESULTS: 181 (59.3%) HCWs reported persisting symptoms attributable to PCS during the examination and 124 (40.7%) HCWs stated no symptoms. In the entire sample, the mean CRP level slightly exceeded the normal range (6.63 mg/L, 95% confidence interval [CI] 5.96-7.3) while all other laboratory results were within the normal range. No statistically significant differences in laboratory results were revealed between both subgroups except for the mean Ig levels, which were higher in HCWs with PCS. The average number of symptoms of PCS was 1.9 (median 2). The most frequent symptoms of PCS were fatigue that interfered with daily life (47.5%), shortness of breath (38.1%), muscle or joint aches (16%), loss of smell (14.9%), headache (14.9%) and sleep disorders (11%). The only statistically significant predictors of PCS were female sex (odds ratio [OR] 1.48, 95% CI 1.059-2.067, p = .022) and increasing age (OR 1.04, 95% CI 1.01-1.07, p = .008). CONCLUSIONS: PCS appears to be a prevalent condition determined by female sex and increasing age.

Changes in ambulance departures for assault calls during COVID-19 pandemic restrictions.

Restrictions related to COVID-19 changed the daily behavior of people, including the expression of violence. Although an increased incidence of violent behavior, especially domestic violence, was expected during the pandemic, retrospective analyses have yielded mixed results. Records of ambulance departures to address injuries caused by assaults in the Pilsen region, Czech Republic, during the restrictive measures during the national state of emergency were compared to data from 3 previous years using general linear models. The number and severity of assaults were analyzed for the whole sample and separately for patients of either sex, for residential or nonresidential locations, and for domestic violence. Controlling for the seasonal effects, the number of assaults decreased by 39% during the pandemic restrictions compared to the 3 previous years. No difference was found between the effects of restrictions on assaults resulting in an injury of a male or female patient. The decrease was specifically pronounced in the sample of assaults in nonresidential locations, while no effect of restrictions was observed in assaults in residential locations and domestic assaults. Pandemic restrictions were associated with a decreased incidence of violent assaults that required ambulance services. Although the incidence decreased especially in those assaulted outside of their homes, we found no support for an increase in domestic violence or violence against women. Pandemic restrictions may have served as a protective rather than a risk factor for assaults severe enough to warrant a call for ambulance services.

SARS-CoV-2 Specific Humoral Immune Responses after BNT162b2 Vaccination in Hospital Healthcare Workers.

BACKGROUND: COVID-19 pandemic has led to a loss of human life in millions and devastating socio-economic consequences worldwide. So far, vaccination is the most effective long-term strategy to control and prevent severe COVID-19 disease. The aim of the current study was to evaluate the humoral immune responses raised against the BNT162b2 vaccine in hospital healthcare workers. METHODS: Total number of 173 healthcare workers enrolled in the study. Their blood samples were collected in three different time intervals after the second SARS-CoV-2 vaccination and evaluated by the ELISA method to detect anti-spike protein IgM and IgG antibodies. The baseline characteristics of all participants were collected using questionnaires and were evaluated for finding any significant data. RESULTS: Our results demonstrated that the levels of antibodies were higher in the young group (21-30 years old) and also among male participants. Moreover, the highest levels of antibodies were detected from the group that received the third shot vaccination. CONCLUSIONS: Our results indicate that age, gender and third-dose vaccination can affect the levels of humoral immune responses against the BNT162b2 vaccine in healthcare workers.

Pharmacokinetics of Intramuscularly Administered Thermoresponsive Polymers.

Aqueous solutions of some polymers exhibit a lower critical solution temperature (LCST); that is, they form phase-separated aggregates when heated above a threshold temperature. Such polymers found many promising (bio)medical applications, including in situ thermogelling with controlled drug release, polymer-supported radiotherapy (brachytherapy), immunotherapy, and wound dressing, among others. Yet, despite the extensive research on medicinal applications of thermoresponsive polymers, their biodistribution and fate after administration remained unknown. Thus, herein, they studied the pharmacokinetics of four different thermoresponsive polyacrylamides after intramuscular administration in mice. In vivo, these thermoresponsive polymers formed depots that subsequently dissolved with a two-phase kinetics (depot maturation, slow redissolution) with half-lives 2 weeks to 5 months, as depot vitrification prolonged their half-lives. Additionally, the decrease of TCP of a polymer solution increased the density of the intramuscular depot. Moreover, they detected secondary polymer depots in the kidneys and liver; these secondary depots also followed two-phase kinetics (depot maturation and slow dissolution), with half-lives 8 to 38 days (kidneys) and 15 to 22 days (liver). Overall, these findings may be used to tailor the properties of thermoresponsive polymers to meet the demands of their medicinal applications. Their methods may become a benchmark for future studies of polymer biodistribution.

What are the real associations of homeostasis model assessment (HOMA) with body mass index and age?

INTRODUCTION: Insulin resistance (IR), a key pathogenesis mechanism of metabolic disorders, can be tested using homeostatic model assessment (HOMA). HOMA-IR quantifies peripheral tissue IR, whereas HOMA-ß determines insulin secretion. The cross-sectional study aimed to examine non-linear associations of HOMA indices with age when adjusting for body mass index (BMI), and thus to investigate the indices' ability to reflect the real development of glucose metabolism disorders over time. MATERIAL AND METHODS: The sample comprised 3406 individuals without diabetes mellitus (DM) divided into those with normal glucose metabolism (NGT, n = 1947) and prediabetes (n = 1459) after undergoing biochemical analyses. Polynomial multiple multivariate regression was applied to objectify associations of HOMA with both age and BMI. RESULTS: Mean values of HOMA-IR and HOMA-ß in individuals with NGT were 1.5 and 82.8, respectively, while in prediabetics they were 2.2 and 74.3, respectively. The regression proved an inverse non-linear dependence of pancreatic b dysfunction, expressed by HOMA-ß, on age, but did not prove a dependence on age for HOMA-IR. Both indices were positively, statistically significantly related to BMI, with a unit increase in BMI representing an increase in HOMA-IR by 0.1 and in HOMA-ß by 3.2. CONCLUSIONS: The mean values of HOMA indices showed that, compared with NGT, prediabetes is associated with more developed IR but lower insulin secretion. Both HOMA-IR and HOMA-b are predicted by BMI, but only HOMA-ß is predicted by age. HOMA indices can reflect non-linear, closer-to-reality dependencies on age, which in many epidemiological studies are simplified to linear ones. The assessment of glucose metabolism using HOMA indices is beneficial for the primary prevention of IR and thus DM.

Relationship between Acute-Phase Symptoms and Immunoglobulin G Seropositivity up to Eight Months after COVID-19.

Background and Objectives: Given the limited knowledge of antibody responses to COVID-19 and their determinants, we analyzed the relationship between the occurrence of acute-phase symptoms and infection-induced immunoglobulin (Ig) G seropositivity up to 8 months post-symptom onset. Materials and Methods: In this cross-sectional study, 661 middle-aged unvaccinated healthcare workers (HCWs) were interviewed about the presence of symptoms during the acute phase of their previously confirmed COVID-19 and were tested for specific IgG, targeting the spike protein (S1 and S2). The dependence of seropositivity on the symptom occurrence was explored through multiple logistic regression, adjusted for the interval between symptom onset and serology testing, and through classification and regression trees. Results: A total of 551 (83.4%) HCWs showed seropositivity and, inversely, 110 (16.6%) HCWs were seronegative. The chance of IgG seropositivity was increased by dyspnea (odds ratio (OR) 1.48, p < 0.001) and anosmia (OR 1.52, p = 0.021). Fever in HCWs with dyspnea resulted in the highest detected seropositivity rate, and anosmia in HCWs without dyspnea significantly increased the proportion of seropositivity. Conclusion: Clinical manifestation of the acute phase of COVID-19 predisposes to the development of infection-induced antibody responses. The findings can be applied for assessing the long-term protection by IgG, and thus, for creating effective surveillance strategies.

The kinetics and predictors of anti-SARS-CoV-2 antibodies up to 8 months after symptomatic COVID-19: A Czech cross-sectional study.

The presence of neutralizing SARS-CoV-2-specific antibodies indicates protection against (re)infection, however, the knowledge of their long-term kinetics is limited. This study analyzed the presence of COVID-19-induced antibodies in unvaccinated healthcare workers (HCWs) over the period of 1-8 months post symptom onset (SO) and explored the determinants of persisting immunoglobulin (Ig) seropositivity. Six hundred sixty-two HCWs were interviewed for anamnestic data and tested for IgG targeting the spike protein (S1 and S2) and IgM targeting the receptor-binding domain. A Cox regression model was used to explore potential predictors of seropositivity with respect to the time lapse between SO and serology testing. 82.9% and 44.7% of HCWs demonstrated IgG and IgM seropositivity, respectively, with a mean interval of 83 days between SARS-CoV-2 detection and serology testing. On average, HCWs reported seven symptoms in the acute phase lasting 20 days. IgG seropositivity rates among HCWs decreased gradually to 80%, 50%, and 35% at 3, 6, and 8 months after SO, while IgM seropositivity fell rapidly to 60%, 15%, and 0% over the same time intervals. The number of symptoms was the only predictor of persisting IgG seropositivity (odds ratio [OR] 1.096, 95% confidence interval [CI] 1.003-1.199, p = 0.043) and symptom duration a predictor of IgM seropositivity (OR 1.011, 95% CI 1.004-1.017, p = 0.002). Infection-induced anti-SARS-CoV-2 IgG rates drop to a third in seropositive participants over the course of 8 months. Symptom count and duration in the acute phase of COVID-19 are both relevant to the subsequent kinetics of antibody responses.

Motivation to COVID-19 Vaccination and Reasons for Hesitancy in Employees of a Czech Tertiary Care Hospital: A Cross-Sectional Survey.

High vaccination coverage among healthcare workers (HCWs) is crucial for managing the COVID-19 pandemic. The aim was to determine the demand for vaccination among all employees (n = 4553) of a tertiary care hospital after several weeks of the vaccine's availability, and to analyze motives for acceptance and reasons for hesitancy through an anonymous online questionnaire. Upon the completion of data collection, the hospital's vaccination coverage was at 69.8%. A total of 3550 completed questionnaires were obtained (2657 from vaccinated, 893 from unvaccinated employees). Significant predictors of vaccine acceptance were: age (odds ratio (OR) 1.01, 95% confidence interval (CI) 1.01-1.02), sex (OR (females) 0.58, 95% CI 0.45-0.75), job type (OR (non-physician HCWs) 0.54, 95% CI 0.41-0.72; OR (non-HCWs) 0.51, 95% CI 0.37-0.71), fear of COVID-19 (OR 1.4, 95% CI 1.34-1.46), history of COVID-19 (OR 0.41, 95% CI 0.34-0.49) and of influenza vaccination (OR 2.74, 95% CI 2.12-3.57). The most frequent motive for acceptance was the effort to protect family members (84%), while concerns about vaccine safety and side effects (49.4%), followed by distrust in the vaccine's efficacy (41.1%) were the top reasons for hesitancy. To increase vaccination coverage among HCWs, it is necessary to raise awareness of vaccine safety and efficacy.

Free triiodothyronine/free thyroxine (FT3/FT4) ratio is strongly associated with insulin resistance in euthyroid and hypothyroid adults: a cross-sectional study.

INTRODUCTION: Insulin resistance (IR) is a key and early pathogenetic mechanism of cardiometabolic diseases with huge potential if detected early and mitigated, for lowering the burden of the disease. Available data are conflicting to what extent adult thyroid dysfunction is associated with IR. Therefore, we aimed to investigate the association and to identify which thyroid parameters are predictors of IR. MATERIAL AND METHODS: After undergoing basic anthropometric and biochemical studies including thyroid hormones, oral glucose tolerance test (OGTT), and insulin, 1425 middle-aged individuals were divided into three groups according to thyroid parameters: overt hypothyroidism (OH), subclinical hypothyroidism (SH), and euthyroidism (EU). RESULTS: The homeostasis model assessment of IR (HOMA-IR), fasting insulin, and two-hour glucose levels of OGTT showed a steady, yet insignificant, increase from EU through SH to OH. The strongest noted correlations were those of insulin levels with free triiodothyronine/free thyroxine (FT3/FT4) ratio (r = 0.206, p < 0.001) and FT3 (r = 0.205, p < 0.001). Also in the case of HOMA-IR, the only statistically significant correlations were observed for FT3 (r = 0.181, p < 0.001) and the FT3/FT4 ratio (r = 0.165, p < 0.001). Among other thyroid hormones, linear logistic regression proved the FT3/FT4 ratio as the only significant predictor of HOMA-IR (linear coefficient = 5.26, p = 0.027) and insulin levels (linear coefficient = 18.01, p = 0.023), respectively. Thyroid-stimulating hormone was not associated with IR in either correlation or regression analysis. CONCLUSIONS: The FT3/FT4 ratio should be more emphasised in the diagnosis and treatment of thyroid disorders. Patients could benefit from a pharmacological reduction of the FT3/FT4 ratio, potentially leading to a decrease in insulin resistance, and thus a corresponding decrease in the risk of the cardiometabolic diseases.

Monitoring of Early Changes of Circulating Tumor DNA in the Plasma of Rectal Cancer Patients Receiving Neoadjuvant Concomitant Chemoradiotherapy: Evaluation for Prognosis and Prediction of Therapeutic Response.

Introduction: Patients with locally advanced rectal cancer (LARC) are undergoing neoadjuvant chemoradiotherapy (NCRT) prior to surgery. Although in some patients the NCRT is known to prevent local recurrence, it is also accompanied by side effects. Accordingly, there is an unmet need to identify predictive markers allowing to identify non-responders to avoid its adverse effects. We monitored circulating tumor DNA (ctDNA) as a potential liquid biopsy-based biomarker. We have investigated ctDNA changes plasma during the early days of NCRT and its relationship to the overall therapy outcome. Methods and Patients: The studied cohort included 36 LARC patients (stage II or III) undergoing NCRT with subsequent surgical treatment. We have detected somatic mutations in tissue biopsies taken during endoscopic examination prior to the therapy. CtDNA was extracted from patient plasma samples prior to therapy and at the end of the first week. In order to optimize the analytical costs of liquid-biopsy testing, we have utilized a two-level approach in which first a low-cost detection method of denaturing capillary electrophoresis was used followed by examination of initially negative samples by a high-sensitivity BEAMING assay. The ctDNA was related to clinical parameters including tumor regression grade (TRG) and TNM tumor staging. Results: We have detected a somatic mutation in 33 out of 36 patients (91.7%). Seven patients (7/33, 21.2%) had ctDNA present prior to therapy. The ctDNA positivity before treatment reduced post-operative disease-free survival and overall survival by an average of 1.47 and 1.41 years, respectively (p = 0.015, and p = 0.010). In all patients, ctDNA was strongly reduced or completely eliminated from plasma by the end of the first week of NCRT, with no correlation to any of the parameters analyzed. Conclusions: The baseline ctDNA presence represented a statistically significant negative prognostic biomarker for the overall patient survival. As ctDNA was reduced indiscriminately from circulation of all patients, dynamics during the first week of NCRT is not suited for predicting the outcome of LARC. However, the general effect of rapid ctDNA disappearance apparently occurring during the initial days of NCRT is noteworthy and should further be studied.

Measles immunity in a Czech tertiary care hospital.

BACKGROUND: Given the increasing incidence of measles, the aim was to assess the seroprevalence of measles immunity among employees of a Czech tertiary care hospital and to assess their willingness to revaccination. METHODS: 3027 hospital employees (2421 females, 606 males) underwent a serological analysis of their measles antibody levels with an option of revaccination in case of an insufficient level. RESULTS: The median age of participants was 42 years. Seropositivity was noted in 54% of the participants, with the antibody values higher in the oldest study participants and with a decrease around the birth year 1968. Logistic regression analysis confirmed a significant relationship of seropositivity with age (odds ratio 0.97, p < 0.005). Out of the seronegative, 80.9% individuals got revaccinated. CONCLUSIONS: 46% of the participants did not reach a sufficient antibody level set by the assay's manufacturer. Although the routine vaccination system is well established it may be ineffective.

Optimal Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Cut-Offs: A Cross-Sectional Study in the Czech Population.

Background and Objectives: The key pathogenetic mechanism of glucose metabolism disorders, insulin resistance (IR), can be assessed using the Homeostasis Model Assessment of IR (HOMA-IR). However, its application in clinical practice is limited due to the absence of cut-offs. In this study, we aimed to define the cut-offs for the Czech population. Methods: After undergoing anthropometric and biochemical studies, the sample of 3539 individuals was divided into either nondiabetics, including both subjects with normal glucose tolerance (NGT, n = 1947) and prediabetics (n = 1459), or diabetics (n = 133). The optimal HOMA-IR cut-offs between subgroups were determined to maximize the sum of the sensitivity and specificity for diagnosing type 2 diabetes mellitus (T2DM) or prediabetes. The predictive accuracy was illustrated using receiver operating characteristic (ROC) curves. Logistic regression was performed to assess the association between a target variable (presence/absence of T2DM) depending on the HOMA-IR score as well as on the age and sex. Results: The HOMA-IR cut-off between nondiabetics and diabetics for both sexes together was 3.63, with a sensitivity of 0.56 and a specificity of 0.86. The area under the ROC curve was 0.73 for T2DM diagnosing in both sexes. The HOMA-IR cut-off between the NGT subjects and prediabetics was 1.82, with a sensitivity of 0.60 and a specificity of 0.66. Logistic regression showed that increased HOMA-IR is a risk factor for the presence of T2DM (odds ratio (OR) 1.2, 95% confidence interval (CI) 1.14-1.28, p < 0.0001). The predictive ability of HOMA-IR in diagnosing T2DM is statistically significantly lower in females (OR 0.66, 95% CI 0.44-0.98). The results are valid for middle-aged European adults. Conclusions: The results suggest the existence of HOMA-IR cut-offs signaling established IR. Introduction of the instrument into common clinical practice, together with the known cut-offs, may contribute to preventing T2DM.