Regarding musculoskeletal conditions, patient’s psychological distress, are shown to be associated with higher disability. Cervical radiculopathy (CR) and carpal tunnel syndrome (CTS), are two conditions caused by entrapment of cervical nerve roots and carpal median nerve, respectively. This study aims to investigate the association of psychological factors including depression, anxiety, and pain catastrophizing, with measures of upper limb patient-reported and performance-based disability, in patients with CR, and compare the obtained results with our similar study on CTS.In a cross-sectional study, we recruited 92 patients with CR, and investigated their disability level using patient-reported questionnaires  and pain Likert Scale) and by measuring grip and pinch strength. We also assessed their psychological status with Hospital Anxiety and Depression Scale questionnaire for depression (HADS-D) and anxiety (HADS-A) and also Pain Catastrophizing Scale (PCS) tools. We performed correlational coefficient analysis between disability and psychological scores and regression analysis of dependent variables  and independent  variables. Finally, Z observed value was calculated to compare correlational coefficients between two diseases of CTS and CR.r = 0.49, 0.37, 0.38 for HADS-A, HADS-D and PCS, respectively; p < 0.001 for all three). HADS-A also significantly correlated with VAS pain score  and grip strength . Linear regression analysis revealed that anxiety has a notable value for DASH and VAS pain scores as well as grip strength. Fisher’s r correlation coefficient to z transformation, revealed that there was no difference between two diseases of CTS and CR in terms of the resulted r coefficients from correlational coefficient analysis between disability and psychological distress.The results of the correlational coefficient analysis indicate that all three HADS-A, HADS-D and PCS scores correlated with DASH score .The online version contains supplementary material available at 10.1186/s12891-022-05593-2. Cervical Radiculopathy (CR) is a common clinical condition , resultiCarpal tunnel syndrome (CTS) is a common compressive median neuropathy, as the nerve transverses through the wrist. Radicular discomfort, paresthesia, and numbness may be felt distal (hand) or proximal (arm) to the wrist in the median nerve territory . Women aFollowing a similar study on the correlation between disability and psychological factors in patients with Carpal Tunnel Syndrome (CTS) , the curWe therefore asked: What are the relationships among validated scores for (1) depression, (2) anxiety, (3) pain catastrophizing and measures of upper limb patient-reported and performance-based disability, in patients with CR? What is the (4) simultaneous association of psychological factors on disability in patients with CR? (5) How are the results of this study, with regard to the correlation between patients’ disability and psychological factors, comparable to CTS in a similar study ? This laThis cross-sectional study was carried out in an urban tertiary hospital in 2019. Prior to commencing the study, ethical approval was obtained from the related research ethics committee (the ethics code is removed due to issues with blinding), and the study was conducted in accordance with the ethical standards in the 1964 Declaration of Helsinki.We recruited from patients who were clinically diagnosed as having CR , and subWe created the data sheet where we gathered demographic data including patients’ personal  and medical  information. We also assigned each patient a code in order to protect their privacy and to prevent exposure of their names. On arrival at the centre, patients’ upper limbs were first assessed using both bilateral EMG results and dynamometer in order to examine grip and pinch force. For the purpose of clinically determining participants’ limb disability, patients were then asked to fill out the Quick DASH questionnaire. Furthermore, the questionnaires of HADS, PCS and Likert pain score were filled out in the same visit session. In case of confirmed bilateral radiculopathy, the more involved limb according to EMG-NCS result was considered for further analysis.We used a Dantec Counterpoint or Keypoint Electro-myographic machine for this research. In SNCV, filter settings ranged from 20 to 2000 Hz, but in MNCV, filter settings ranged from 20 to 10,000 Hz. The limbs were adequately warmed to keep the skin between 32 and 34 degrees Celsius. The deltoid (C5-C6), biceps (C5-C6), flexor carpi radialis (C6-C7), extensor digitorum (C6-C8), dorsal interosseous (C8-T1), and opponense pollicis (C8-T1) electromyography, were the least muscles studied in EMG. Abnormal EMG is defined as neurogen findings in a specific myotome consistent with cervical root lesion. Almost all NCS studies (F wave) were normal.Eleven-item quick DASH questionnaire is an abbreviated version of original DASH . The queIn order to quantify the severity of pain, 11 point Likert is used as a simple scale which scores pain severity from 0 (no symptom) to 10 (worst symptom) on a 11-point basis .A hand dynamometer is an apparatus for determining isometric grip force (hand grip strength). By using a hydraulic hand dynamometer , we measured patients’ isometric grip force (hand grip strength) in kilograms. Patients squeezed the dynamometer three times in Jamar position 2 , applyinTo quantify and measure depression and anxiety of outpatients in clinics, the HADS questionnaire was designed with two subscales. Both subscales of HADS-D (depression) and HADS-A (anxiety) consist of seven items, and patients can respond on a scale of zero to three where zero designates no depression or anxiety and three designates their highest level. In this study, a translated version of this questionnaire which has been validated was used. To interpret patient scores, total subscale scores of 0–7 are considered as Normal, 8–10 as Borderline Abnormal (borderline case) and 11–21 as Abnormal (case). The MCIDs is 1.7 points from the distribution-based, anchor-based, and Delphi-based findings .As an attempt to evaluate the mental state of patients in pain, the 13-item instrument PCS was designed with three subscales assessing rumination, magnification and helplessness. Taking this test, patients need to answer how much they have experienced each of the 13 thoughts and emotions while being in pain. On its 5-point scale answer sheet, they can choose among 0  to 4 , and their total scores may range from 0 to 52 . In thisAll analyses were carried out using SPSS software (version 22). The scores of questionnaires, DASH, HADS, PCS and VAS, recorded from a total of 100 in order to make analysis and interpretation easier.P value and r coefficient were calculated. Adopting the linear regression model, it was possible to identify associated psychological factors and score of DASH, pain Likert, grip and pinch strength. P value significance level was set at 0.05. The secondary goal was to compare the correlational results between patients with CR and CTS (using our previous study results). To achieve this, Fisher’s r correlation coefficient to z transformation was conducted and z values (z1 and z2) that correspond to the correlation coefficients (r1 and r2) were calculated, and finally the comparison was conducted based on achieved Z observed value.We have reported the quantitative data as mean (standard deviation) for normally distributed data and as median (min - max) for non-normally distributed data. Our primary study goal was to evaluate the correlation of depression, anxiety and pain catastrophizing with affected limb disability. To achieve this, bivariate correlational analysis between psychological (HADS and PCS scores) and disability  parameters was performed using Spearman test. Then, the related N = 11, 12%), and depression was the most common psychological disorder . Of note, there were patients with more than one medical comorbidity, psychological comorbidity or previous received treatment, which is why in the related table sections, the sum of subsections are more than 100%  of whom were women. Table p = 0.001]). There was no relationship between the HADS-D and other studied variables in the analysis , pain score (correlation coefficient = 0.41 [p < 0.001]), and grip force (correlation coefficient = − 0.25 [p = 0.016])  Table .Table 3Pp < 0.001]) and pain score (correlation coefficient = 0.38 [p < 0.001])  Table .P value < 0.001) . Regression analysis shows that using HADS-A, HADS-D and PCS as three predictors was significantly better than prediction without them and using only the mean in the model  had positive correlation with patient-reported disability (DASH) in patients with cervical radiculopathy. It has previously been found that disability in patients with CTS has similar association with mental distress. This finding thus provides support for examination and treatment of mental distress signs in patients with marked disability. As Nikola et al. concluded, this relationship maybe due to the correlation between pressure pain threshold (PPT) measured by the algometer and anxiety/depression, using the same questionnaires as ours (HADS) . ConsistThere are several studies indicating that psychological factors are also important predictors in surgical treatment outcome or post operation disability in CR patients , 29–31. As an interesting finding, we also found a modest correlation between anxiety and grip strength as well as anxiety also values for grip force variance. Another study has also found a similar negative correlation between depression/anxiety and hand strength but in stroke patients . PreviouWe observed that patient-reported disability scores in patients with either CTS or CR similarly associate with psychological parameters, and there is no notable difference in two conditions’ r coefficients. Anxiety seems to be the parameter which correlates stronger with disability in patients with either of these diseases. The only difference between the results of these two studies is the negative correlation of anxiety with grip strength in patients with CR. While psychological factors were only associated with patient-reported disability scores in patients with CTS , they alThe results of this investigation show that anxiety correlates with disability parameters of DASH, pain, and grip scores in patients with CR. In addition, the pattern of correlation between psychological and disability factors are almost similar between patients with CR and CTS.Based on the present results, we cannot conclude if mood disorders result in more disability or disability leads to depression and anxiety. This remains to be determined in further longitudinal studies. Furthermore, it is also unclear whether psychological intervention can improve pain and functional ability post-operatively.Additional file 1.


Missense variants were present in both conditions, presumably with loss- or gain-of-functions. KCNK18 nonsense/frameshift variants were found in painless/painful-DN, making a causal role in pain less likely. Surprisingly, premature stop-codons with likely nonsense-mediated RNA-decay were more frequent in painful-DN. Although limited in number, painful-DN patients with ion channel gene variants reported higher maximal pain during the night and day. Moreover, painful-DN patients with TRP variants had abnormal thermal thresholds and more severe pain during the night and day. Our results suggest a role of ion channel gene variants in neuropathic pain, but functional validation is required.Neuropathic pain is common in diabetic peripheral neuropathy (DN), probably caused by pathogenic ion channel gene variants. Therefore, we performed molecular inversion probes-next generation sequencing of 5 transient receptor potential cation channels, 8 potassium channels and 2 calcium-activated chloride channel genes in 222 painful- and 304 painless-DN patients. Twelve painful-DN (5.4%) patients showed potentially pathogenic variants  in ANO3 ( Neuropathic pain (NeuP) is caused by damage or disease of the somatosensory nervous system . Around Several small-scale studies have investigated why some patients with diabetic neuropathy develop painful-DN, while others do not . Female SCN9A gene encoding Nav1.7, in contrast, led to congenital insensitivity to pain, while gain-of-function mutations have been linked to a spectrum of pain disorders, including painful-DN [v1.7 variants report more severe burning pain and increased pressure stimuli sensitivity, compared to painful- DN patients without the SCN9A variant [In recent years, genetic causes of NeuP have partially been resolved, and next-generation sequencing (NGS) has been increasingly performed to identify genes and genetic variants associated with NeuP . Pathoge variant ,11. Howe2+-activated Cl- channel from the ANO family, which interacts with TRPV1, leading to pain enhancement in sensory neurons, while ANO3 regulates pain processing via increasing the Slack channels’ activity in DRG neurons [Apart from VGSCs, other ion channels are also essential for proper functioning of the nervous system . It has  neurons ,17,18.Our hypothesis is that in addition to VGSCs, variants in other ion channels are involved in painful-DN. Therefore, we analyzed seven Kv, five TRP, two ANO and one HCN ion channel genes expressed in peripheral nerves, using single molecule molecular inversion probes-next generation sequencing (smMIPs-NGS) in patients with painful-DN and painless-DN. The painless-DN group was included to identify variants linked to the absence of pain, which may play role in pain resilience and to exclude common variants present frequently in both patient groups. We also assessed if these variants were linked to specific clinical manifestations.In total, 612 patients with DN were included, 393 from the Heinrich Heine University , and 219 from the University of Manchester . Of these, 86 patients were excluded, due to low DNA quality, MIP failure, incomplete clinical data or withdrawal of formal consent. Among the enrolled patients, 222 had painful-DN and 304 had painless-DN. The mean age at recruitment was 64.5 years old (SD +/−11.2 years). Sex distribution in the study group was 372 (70.7%) males versus 154 (29.3%) females. The higher male prevalence was present in both phenotypes. Clinical characteristics of the study population are presented in ANO1, and exon 3 of TRPV1), and MIPs for 14 exons covered the targeted region of > 20×/bp only partially  of 15 ICG, data of 50 samples from 5 different NGS runs were used. An overall coverage of more than 30×/bp was obtained for 93% of the on-target regions. Exons and exon-flanking sequences of ten gene areas have an average coverage of >90%. Four exons had poor coverage (<20×/bp) or were completely missing . The clinical characteristics of painful-DN patients with ICG VUS are presented in n = 9) reported higher mean maximal pain scores during 24 h (PI-NRS 7.2 +/−2.4), compared to patients with painful-DN without an ICG variant . However, due to the small sample size, statistical analysis was not possible . It seems that patients with painless-DN with an ICG VUS variant reported less often autonomic complains, especially diarrhea, dry mouth, orthostatic dizziness, sheet intolerance and restless leg; however, the group size (n = 4) is too small to draw a definite conclusion. The clinical characteristic and autonomic complaints in patients with painless- DN and ICG variant are presented in In 304 patients with painless-DN, 13 different potentially pathogenic heterozygous variants were identified. Fourteen (4.6%) patients had a potentially pathogenic variant in one of the fifteen ICG, but none had more than one ICG variant . In two nd TRPV4 . Seven oANO3, HCN1, KCNK18, TRPA1, TRPM8, TRPV4. Three patients (1.4%) had a potentially pathogenic variant in ANO3, one (0.5%) in HCN1, two (0.9%) in KCNK18, three (1.4%) in TRPA1, three (1.4%) in TRPM8, one (0.5%) in TRPV4. In patients with SFN and NeP, the frequency of  pathogenic variants in the sodium ion channels was slightly higher; 5.1% for SCN9A, 3.7% for SCN10A and 2.9% for SCN11A [ANO1, KCNK18, KCNQ3, TRPA1, TRPM8, TRPV1 and TRPV4. Potentially causative variants were identified in one patient (0.3%) in ANO1, three (1%) in KCNK18, one (0.3%) in KCNQ3, two (0.7%) in TRPA1, one (0.3%) in TRPM8, three (1%) in TRPV1 and three (1%) in TRPV4. Four of these genes  have not been linked to a painful phenotype or to pain insensitivity before in HGMD. We did not find any potentially pathogenic variant in the following six genes from our gene panel: KCNA2, KCNA4, KCNNA, KCNQ5, KCNS1, TRPV3.In our cohort of patients with DN, twelve patients with painful-DN (5.4%) and fourteen patients with painless-DN (4.6%) harbored at least one potentially pathogenic variant in the ICG gene, respectively linked to pain or no pain. Only one patient with painful-DN had two heterozygous variants TRPA1 c.2481del and TRPM8 c.1437G>T. In total, we identified 13 different potentially pathogenic variants in painful-DN located in KCNK18 variants c.414_415del and c.361dup and TRPA1 c.352C>G. Our patients did not report migraines during clinical investigation. However, questions about headaches or migraines were not included in the standard questionnaires and we were not able to contact the patients to confirm the lack of migraine symptoms. The presence of these variants in both phenotypes might be explained by other mutations in the genes not included in our gene panel or non-genetic risk factors contributing to a painful phenotype [SCN10A c.368C>T, VUS and ANO1 c.1892G>A, VUS, and SCN10A c.1141A>G, possibly pathogenic and TRPV4 c.958C>T, VUS.The same missense variants were not present in any of the ICG genes in painful- and painless-DN, with the exception of migraine-related henotype . In two All variants meeting our criteria were variants of uncertain clinical significance, making it difficult to draw a definite conclusion on a causative role. However, this is not surprising, since most of the variants we identified were novel and we could only rely on in-silico predictions without segregation analysis in families or functional studies. The development of NGS and more affordable cost of sequencing have resulted in recent years in the identification of a significant number of VUS and part of them have been proved to be pathogenic over the time .The VUS detected in our study either change the protein via substitutions of conserved amino acids (missense VUS) or are generally predicted to lead to the absence of the protein, because of nonsense mediated decay, triggered by a premature stop codon (nonsense/frameshift VUS). For the latter group, the KCNK18 gene contained premature stop codons in both painful- and painless-DN, making a causal role of haploinsufficiency of these genes on the pain phenotype unlikely. For the other nonsense/frameshift variants, this is not the case. Although NMD is most likely, truncated non-functional protein or alternative processes, such as frameshift mutation-induced alternative translation initiation (fsATI), have also been reported , requiriOverlap exists between the genes with missense mutations in painful- and painless-DN, but this does not disqualify the role they might have, as it has been reported that missense mutations can lead to gain or loss-of-functions with possible opposite effects on pain sensitivity, highlighting the importance of functional effect rather than the variation itself. Additional support for functional relevance is for the 3 VUS in TRPV1 and 1 VUS in ANO3, located in the transmembrane domain, which can directly affect channel properties e.g., channel gating . Two misANO3 gene were detected in painful-DN and one missense heterozygous variant in the ANO1 gene in painless-DN. These genes belong to Ca2+-activated Cl- channels and they are highly expressed in dorsal root ganglia (DRG) [Three missense heterozygous variants in the ia (DRG) ,18. ANO3ia (DRG) ,30. A LOVoltage-dependent potassium channels are crucial for controlling the excitability of nociceptors and pain processing . A heterWe identified several variants located in TRP channels both in painful- and painless- DN. TRPV1, TRPM8, and TRPA1 are thermal and chemical detectors that activate sensory neurons to produce pain, while TRPV4 mediates nociceptive behaviors by hyper- and hypotonic stimuli . Three TSimilar to TRPA1, TRPM8 modulates the cold sensation and its activation produces analgesia in chronic neuropathic pain states ,43. In pTRPV1 and TRPV4 belong to the transient receptor potential vanilloid family and most of the VUS in these genes were present in painless-DN. In total, three missense VUS in TRPV1 were present in painless-DN, all located in the functional domain of the channel; c.1450G>C in transmembrane domain II, c.1781C>T and c.1790C>T both in transmembrane domain IV. Activation of TRPV1 results in the generation of action potentials and in many cases, pain . Moreoven = 9) had higher mean pain scores compared to patients with painful-DN without the potentially causative ICG variant (n = 150). Determining clinically important differences in pain is challenging [Patients with painful-DN with an ICG VUS , Heinrich Heine University, Düsseldorf, Germany or at the University of Manchester, Manchester, United Kingdom. They were examined between June 2014 and September 2016. Only patients aged above 18 years old and those diagnosed with diabetes mellitus type 1 or type 2  were eligible for this study. Demographic data, medical history, age of onset of complaints, duration of symptoms, altered pain sensation and family history were recorded. Pain intensity was evaluated using the 11-point Numerical Rating Scale (PI-NRS) from 0–10, where 0 means “no pain” and 10 refers to “the worst pain imaginable.” For all the patients, informed consent was obtained and a blood sample for genetic analysis was drawn.® device. NeuP was diagnosed as reported before [For the patients with painful-DN, quantitative sensory testing of the lower limb was performed on the dorsum of the foot using the Medocd before . The diad before . The DN ® Blood Core Kit , according to the manufacturer’s instructions at Maastricht UMC+, and IRCCS Neurological Institute Carlo Besta. DNA samples were coded and stored in the central DNA bank at Maastricht UMC+ and IRCCS Neurological Institute Carlo Besta in −20 °C.Genomic DNA was extracted from whole blood using the NucleoSpin8 Blood Isolation Kit  or QIAamp DNA Blood Maxi Kit, PuregeneGene candidates for smMIPs-NGS were selected based on their role with pain in OMIM and the literature, high expression in peripheral nerve DRG and/or trigeminus cells, and by comparative and integrative genomics, with SCN9A co-expression described by Szklarczyk et al. . The fifhttp://shendurelab.github.io/MIPGEN/, accessed on 2 September 2014). The number smMIPs per gene and size of targeted coding region per gene have been given in In total, 295 single-molecule molecular inversion probes (smMIPs) were designed to capture exon and exon-flanking intron sequences (+/−20 bps) of 15 ion channel gene candidates , using aSmMIP-NGS was performed as described before . In brieSequenced data were analyzed using an smMIPs-NGS pipeline developed by Maastricht UMC+ in collaboration with Radboud University . The smMExonic variants and exonic flanking regions (+/−20 bps) with >20× coverage and an alternative variant call of >30% were analyzed in further detail. Common SNPs were excluded from the analysis; only variants with dbSNP < 5%, ExAC < 5% and in house database of 12,244 exomes < 1% were included. Alamut Visual  software was used for variant interpretation. Variants were classified according to the practice guidelines of the Association for Clinical Genetic Science (ACGS) . Potentit-test was used to analyze continuous variables and chi-square test was applied for categorical variables. The significance level was defined as 0.05.The independent Student’s


RASS results correlated significantly (p < 0.05) and positively with the results of the BPS and CCPOT. A strong correlation was found between the results of both scales at each stage of the study (R = 0.622–0.907). Conclusions: Nursing procedures are a source of pain in analgosedated patients. The BPS and CCPOT scales are useful tools for assessing the occurrence of pain in mechanically ventilated patients, including those in deep sedation.Background: Intensive Care Unit (ICU) patients often experience pain, especially during diagnostic, nursing, and therapeutic interventions. Pain assessment using the Behavioral Pain Scale (BPS) and Critical Care Pain Observation Tool (CCPOT) are recommended, but they are difficult to do in patients undergoing deep sedation. This study analyzed the usefulness of the BPS and CCPOT scales in assessing pain among patients with varying degrees of sedation. Methods: In 81 mechanically ventilated and sedated ICU patients, 1005 measurements were performed using the BPS and CCPOT scales. The study was conducted by 3 trained observers 3 times a day . The Richmond Agitation-Sedation Scale (RASS), the Simplified Acute Physiology Score (SAPS II), and the Acute Physiology and Chronic Health Evaluation (APACHE II) were also analyzed from medical records as well as information on the length of hospitalization and treatment. Results: It was shown that signs of pain increased significantly ( In the Intensive Care Unit (ICU), emphasis is placed on the control of pain, agitation, delirium, patient immobility, and sleep (PADIS) . PADIS iIn line with the 2018 Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients (PADIS) in the ICU the most accurate and reliable pain assessment tool among patients unable to communicate with the therapeutic team is still the Behavioral Pain Scale (BPS) and the Critical Care Pain Observation Tool (CCPOT) . In addiIn order to standardize the treatment and care of ICU patients, the ABCDEF algorithm is used . It involves pauses in sedation, shallow sedation with optimal analgesia associated with spontaneous breathing attempts, early extubation, and mobilization of a cooperating patient, delirium control, and family involvement in care ,20. SimiThe authors of the e-CASH guidelines note, however, that deep sedation is justified in certain groups of patients, such as those with severe respiratory failure with dyssynchrony, during the administration of muscle relaxants, in an epileptic state, in surgically treated patients requiring absolute immobilization, and in those with severe brain damage with intracranial hypertension. Sedation in favor of analgesia should be avoided in the remaining groups of patients . There aThe observational study was carried out in 2017–2019 in the Intensive Care Unit of the University Hospital in Krakow after obtaining the consent of the bioethics committee (consent No. 1072.6120.161.2017). The study group consisted of 81 patients-34 (41.97%) women and 47 (58.03%) men aged 56 to 75.8 (mean age 63.1 ± 17.21). The study included adult patients unable to self-report pain, requiring sedation  and analgesia, mechanically ventilated, hemodynamically stable, and staying in the ICU for at least 48 h. The study excluded patients with paresis or paralysis of the upper and/or lower limbs, receiving neuromuscular blocking drugs, after sudden cardiac arrest (SCA), and after injuries that prevented pain assessment .The researchers did not intervene in the treatment regimen of the study patients. Prior to our study, monitoring of sedation and analgesia with standardized tools had not been routinely used in the studied ICU. Analgesia and sedation in patients were considered individually and adjusted to the patient’s clinical condition, as stated in the DAS guideline , and in The study used behavioral pain scales, meaning the BPS, CCPOT and RASS scale  to assess the depth of sedation. In addition, data from medical records were analyzed, such as patient records, information on the length of hospitalization, sedation and analgesics, and the risk of death scales through the Simplified Acute Physiology Score (SAPS II) and Acute Physiology and Chronic Health Evaluation (APACHE II).The Polish version of the CCPOT is a useful and reliable tool for analyzing pain in critically ill, intubated patients using analgosedation without hypnosis protocol based on opioid infusions . The PolThe study was conducted simultaneously by three independent observers trained theoretically and practically in the uniform use of the BPS and CCPOT scales. The researchers did not consult the results of the assessment with each other. The observation period was 24 h (randomly selected from the entire stay in the ward), during which pain was assessed three times a day  in the patients .Rest meant no medical or nursing intervention for at least 30 min. Interventions in which pain was assessed included the procedure of evacuating secretions from the bronchial tree, changing the dressing on a surgical wound, or repositioning the patient in bed. The evaluation after the intervention was carried out for dozen to several dozen minutes without stimulation from external stimuli. Since in some patients, during the scheduled observations, there were disrupting factors, such as withdrawal of sedation on the day of measurement, diagnostic and surgical procedures with the use of muscle relaxants, in-hospital transport for tests or procedures, the analysis finally included 1005 measurements meeting all the correct criteria.The R CRAN software for Windows  was used for statistical analysis. The analysis of quantitative variables  was performed by calculating the mean, standard deviation, median, quartiles, minimum and maximum. The analysis of qualitative variables  was performed by calculating the number and percentage of occurrences of each value.The comparison of the values of the qualitative variables in the groups was performed using the chi-square test (with Yates’ correction for 2 × 2 tables) or Fisher’s exact test, where low expected frequencies appeared in the tables. The comparison of the values of quantitative variables in the two groups was performed using the Mann-Whitney test. Correlations between quantitative variables were analyzed using the Spearman correlation coefficient. Non-parametric methods were chosen since all quantitative variables were not normally distributed, by definition .p < 0.05.The analysis of the influence of quantitative variables on a dichotomous (binary) variable was performed using the logistic regression method. The results are presented in the form of OR (odds ratio) with a 95α% confidence interval. The level of significance was p < 0.001). Moreover, the length of hospitalization negatively correlated with the SAPS II scores (p < 0.05). The more severe the patients’ health condition and the higher the risk of death on this scale, the shorter the hospitalization, often ending in death. A similar relationship has not been demonstrated with the APACHE II scale. Most of the patients required deep sedation . On the APACHE II scale, the respondents obtained from 20 to 29 points, on average 25.43 ± 9.39 points in the assessment of the severity of their condition and 30–55 (average 42.73 ± 24.38) points in assessing the risk of death. The SAPS II scores, however, came out to 48–70 (average 59.3 ± 16.57) points and 41–85 (average 60.96 ± 24.42) points respectively. The risk of death increased significantly with the age of the studied patients . The sedating drugs (apart from Ketamine) used in the study group were Propofol and Midazolam, and occasionally neuroleptics were also administered . Data on average doses of analgesics and sedatives used intravenously in continuous infusion in the study group of patients are presented in In the vast majority of measurements, patients had no signs of pain, except during the interventions. The no-pain scores were very similar on both scales . In about 1/3 of the measurements, signs of pain were observed in patients during the intervention .p < 0.001), and then returned to values close to resting during third observation , it was shown that the signs of pain increased significantly during interventions among patients (p ˂ 0.05) and positively with the BPS and CCPOT scores at all stages of the study  independent predictor of an increase in pain intensity during an intervention. The regression parameter for the BPS was 0.254, so the higher the RASS score , the more visible signs of pain during an intervention were observed . In the case of the CCPOT, the regression parameter is 0.363, so for each RASS point, there was an average increase of 0.363 points in pain. Yet, no differences were found related to the supply of specific analgesics and sedatives (p > 0.05).Moreover, it was found that the degree of sedation of patients, meaning the RASS score, was a significant  and after interventions (p = 0.054 for the CCPOT and p = 0.087 for the BPS). On the other hand, the results of the scales during the painful procedures were similar in both sexes (p > 0.05).Analyzing the obtained data in the subgroups of women and men, it was found that men showed not significantly higher scores than women, both before (p = 0.027). Thus, the intensity of the signs of pain was not related to the age of the patients during the procedures, but younger patients manifested pain of a slightly greater intensity than older patients before and after the interventions  and in the case of the CCPOT, both before the intervention (p = 0.03) and during the intervention  . UnrelieThe BPS and CCPOT are scales recognized for pain testing in patients unable to verbalize pain, in line with the PADIS  recommenThere are also differences in opinions about the validity of using these scales in unconscious and deeply sedated patients. According to some authors, both of these scales are equally useful for testing pain in patients with varying degrees of analgesia or sedation , both coAccording to other authors, however, there are differences in the results of these scales of conscious and unconscious/sedated and unsedated patients, both before and after nursing procedures ,9. The hp < 0.001) [p < 0.0001). Sedated patients, including some profoundly sedated, with a RASS score of less than −3 showed signs of pain during painful procedures on both the CCPOT and BPS scores, with less sedation being a significant independent predictor of increased signs of pain.Pain scales are usually tested by comparing the results between a painful and a painless procedure or at rest, as in the study by Rijkenberg et al., where the mean difference between painful and painless procedures was 3.13 ± 1.56 (< 0.001) . In our < 0.001) . CompariA separate issue is the matter of deep sedation in our group of patients. Sedation and analgesia are undoubtedly important elements in the treatment of mechanically ventilated patients in the ICU. Analgosedation provides patients with comfort, improves patient-ventilator synchrony, reduces anxiety and agitation , allows On the other hand, studies indicate that the use of excessive sedation is a disadvantage. Deep sedation is associated with a prolonged duration of mechanical ventilation, longer stay in the ICU ,39, is aAccording to the e-CASH guidelines, deep sedation is justified in some patients, despite potential side effects e.g., in patients with ARDS and dyssynchrony, treated with muscle relaxants, in surgical patients requiring immobilisation, and with severe brain injury with intracranial hypertension , i.e., iThe two most validated and reliable sedation scales are recommended for use in ICU mechanically ventilated patients-the Sedation Agitation Scale (SAS) and the Richmond Agitation Sedation Scale (RASS) . We usedThe use of deep sedation, although it is not recommended, is a rather common ICU phenomenon in many countries ,38. As sIn our study, most of the patients were deeply sedated (assuming a RASS below −3). ICU practices related to long-term analgosedation (>24 h) were rather typical for Polish hospitals and included opioid, Midazolam and Propofol treatments . Our patp ˂ 0.001), and returned to values close to resting sometime after the intervention was over. This was confirmed by the simultaneous use of the BPS and CCPOT scales and a strong correlation between the results of both scales at each stage of the study, especially evident during painful interventions (r = 0.907).In general, pain was well controlled in the studied patients, because apart from the interventions, they did not show any signs of it according to the adopted criteria . Our study confirms the usefulness of the BPS and CCPOT scales in the assessment of pain in the studied group of patients. Signs of pain, also in patients with RASS scores below −3, were much more visible to independent observers when performing painful procedures in patients than in patients at rest , which may affect pain experience . PerhapsBehavioral pain scales do not allow the assessment of pain sensations in patients who cannot manifest it in any visible way, for example, in patients with limb paralysis or craniofacial injuries. It should be assumed that they also experience pain during nursing, diagnostic and treatment activities , so effective methods of minimizing pain should be implemented.The results of our study, based on more than 1000 measurements by three independent observers, seem to confirm the usefulness of the BPS and CCPOT scales in assessing pain in patients undergoing sedation, including deep sedation, yet they have some limitations. The research was conducted in one center (the Trauma Centre for Emergency and Disaster Medicine), which treated the most seriously ill patients-usually those with multiple and multi-organ injuries, requiring highly specialized monitoring, treatment  and nursing care in which the analgosedation treatment regimen may have differed from that adopted in other ICUs. Therefore, it was not possible to extrapolate the obtained results. Moreover, the profile of the studied ward, large differentiation among patients in terms of disease entities, the related individual selection of analgesia and the interactions of sedatives and analgesics made it impossible to analyze the relationships between the type and doses of analgesics and the results of the BPS, CCPOT and RASS scales. Further research is required.As there are no universal signs of pain, and individual pain management based on different tools is a complex task, it should be entrusted to team members after prior training. In pain assessment, tools should be carefully selected according to the patient’s health situation ,56. It sThe results of the study indicate that some nursing procedures commonly used in the ICU are a source of pain, also in patients undergoing deep sedation and receiving analgesics. The BPS and CCPOT scales are useful tools for assessing the occurrence of pain in this group of patients.


There were also significant differences between gender (p < 0.05) and pain severity (p < 0.01) across the levels of depression. The levels of anxiety, depression, and pain were significant, especially among older patients. These symptoms should be routinely assessed, and further identification of predictors such as socioeconomic status before the procedure is necessary.Coronary artery bypass graft (CABG) surgery patients often present with anxiety and depression. These symptoms coupled with pain are major concerns and are widely reported among CABG patients. The study aimed to evaluate the relationship between psychological distress and patients’ demographic data. This cross-sectional study in which 178 patients from a surgery ward were selected using the census method. Data were collected using the Hospital Anxiety and Depression Scale and the Brief Pain Inventory (Short Form). The participants’ mean age was 57.49 ± 13.78 years. The majority of participants had a moderate level of anxiety (89.3%) and a moderate level of pain interference (74.7%). Significant differences were noted, with a higher proportion of moderate anxiety level participants aged between 60 and 74 years old, married, and with a tertiary level education ( Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality in both developing and developed countries . AccordiPatients scheduled for CABG and those recovering from the surgery may face considerable physical and psychological challenges. In this paper, psychological distress refers to symptoms of anxiety and depression levels alone. Other than psychological distress, pain is also the most common symptom patients seek for treatment. It has been reported by Woldegerima Berhe et al.  that amoIn addressing this situation, nurses are required to assist patients in managing these symptoms during the CABG phase as high levels of anxiety and depression can cause distress to the patients and result in poor outcomes. Patients who are more anxious prior to the CABG procedure would encounter more postoperative pain, higher readmission rates, less long-term relief of cardiac signs and symptoms, and possibly death after discharge . When thThis was a cross-sectional study that utilized structured questionnaires to assess the level of anxiety, depression, and pain among patients undergoing CABG surgery. The study was conducted in the surgical ward of a Tertiary Referral Centre based in Kuala Lumpur, Malaysia, between September 2014 and October 2015. The present report was prepared in keeping with the standards set forth by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement .The research population consisted of randomly selected patients scheduled for CABG surgery. Inclusion criteria were patients aged more than 18 years old, undergoing CABG surgery for the first time, who were alert and aware of time, place, and person, able to write, read and speak in both English and Malay languages; and have no known neurologic problems. Patients who were arranged to undergo emergency surgery and had clinical instability defined as decompensated heart failure or any acute process that causes major symptoms were excluded from this study. The sample size was calculated to be 180 according to the study conducted by Shahmansouri et.al., with prevalence of 39% moderate level of fear (p), 95% confident coefficient (z), and a detection accuracy of 0.07 (d) ,19.One hundred and eighty patients were randomly selected from the CABG waiting list. Those selected were approached to participate in this study; however, two patients refused to participate in the study, leaving a total of 178 CABG patients. Patients undergoing CABG surgery are usually admitted two days before the surgical procedure to allow for physical examination and laboratory studies. On the day before surgery, all participants were given a thorough explanation of the study process before signing consent forms. They also were asked if they were on any treatment for anxiety, depression, or chronic pain. They were expected to complete all of the questionnaires, which took approximately 15 to 20 min. Some patients had to be assisted with the completion of the questionnaire for various reasons including poor eyesight.Three data collection tools were used in the study: The ‘Personal Information Form’ was used to collect patients’ characteristics, the ‘Hospital Anxiety and Depression Scale (HADS) was used to determine the level of anxiety and depression , and theFor the ‘Personal Information Form’, the demographic data, which includes age; gender; marital status; educational level, and monthly income were collected through individual interviews with participants; while medical comorbidities, which include hypertension, diabetes mellitus, history of myocardial infarction, and others  and any treatment for chronic pain before CABG were collected from medical records and patients. The researcher also administered mini-mental state examinations to patients over the age of 65 to ensure that the participants were alert and orientated.The HADS and BPI-SF have been repeatedly validated and demonstrated to be effective screening tools in assessing the presence and severity of both symptoms ,23. The Perceived pain was measured with the Brief Pain Inventory (Short Form) (BPI-SF). It is a well-established eleven-item questionnaire that consists of a pain severity subscale to rate pain severity in four domains  and a pain interference subscale to measure the perceived degree of pain that interferes with daily activities in seven functional domains . Each item is rated on a visual analog scale of 10 cm, where 0 indicates ‘none’ and 10 indicates ‘worst imaginable’. In this study, some of the patients verbalized that the pain was due to chest discomfort, body ache, bowel problems, and musculoskeletal disease. Patients were asked to rate their pain by circling one number that described how the pain has interfered with their life such as their sleep, for over the previous 24 h. The seven BPI interference items were summed, thus generating scores ranging from 0 to 70. The cut points (CP) for BPI among CABG patients are 1–3 for mild pain, 4–6 for moderate pain, and 7–10 for severe pain . CronbacThirty (30) patients undergoing CABG surgery who have the same characteristics as the study sample were invited for the pilot study to check the reliability and suitability of the instrument in the Malaysian setting, using Cronbach’s alpha coefficient. In this study, the internal consistency reliability of Cronbach’s alpha for HADS among CABG patients was 0.74 for anxiety scores and 0.67 for depression. Cronbach’s alpha for the pain-severity and pain-interference score was 0.72 and 0.80, respectively. All the survey sections remain unchanged as the reliability had been demonstrated and face validity established.This study was conducted in accordance with the Declaration of Helsinki and the Caldicott Principle. Meanwhile, ethical approval was obtained from the Medical Research Ethics Committee (MREC) of University Malaya Medical Centre, Kuala Lumpur, Malaysia (MEC ID No. is: 201401-0709), where the study was conducted. Patients received written and verbal information regarding the flow and aims of the study as well as the potential benefit of consenting and participating in the study. Patients were informed that they could withdraw from the study at any time without the need to disclose their reason and that there would be no negative consequences to their medical care. The researcher emphasized that participation in the study was entirely voluntary and that the subject’s confidentiality and anonymity will be assured through the coding of all data. Finally, the safety of the soft and hard copy data was ensured.p-value less than 0.05 indicating statistical significance. The estimation of each predictor  was calculated. Quantitative variables were expressed as mean ± standard deviation.All statistical analyses were carried out via SPSS Software Version 23.0 . The frequencies and significance of psychological symptoms and pain levels were individually calculated through the Chi-square test for dichotomous variables with a The socio-demographic characteristics of the respondents are shown in p < 0.05), with a higher proportion of moderate anxiety level participants (89.3%) being aged between 60 and 74 years old (42.1%), married (73.6%), and those with secondary educational level (64.2%). There were also no remarkable differences in the proportion of the depression level by age group, marital status, education level, medical comorbid conditions, and pain interferences. However, gender (p < 0.05) and pain severity (p < 0.01) differed significantly across the level of depression. A higher proportion of mild depression was found in the male patients (76.6%) and among those who experienced mild pain severity (58.9%).The present study generally showed that a high number of patients undergoing CABG had a moderate level of anxiety, with a HAD-A score ranging from 8 to 14 (89.3%) and mild depression (60%). This is due to patients who are worried and have fear about surgery, chest wound, pain, mobility, and risk of death. Other than that, the increasing tendency towards early discharge from hospitalization and hospital costs can result in increasing psychological symptoms and nursing needs, especially during the homestay period. This finding is consistent with a previous study that showed a higher proportion of patients undergoing CABG surgery experienced increased anxiety because they were thinking about pain and risk of death ,27.p = 0.017). Age is significantly related to anxiety level, but not depression level. According to Weiss et al. [In this study, the association between socio-demographic factors such as age, marital status, and education was found to be significantly associated with anxiety. The patients whose age was 60 to 74 were found to be more anxious compared to the patients whose age was between 15 and 29 years  in our study patients. Based on the level of depression, the results of this study showed that pain severity and gender were significant predictors among CABG patients. A study by Hweidi, Gharaibeh, Al-Obeisat, and Al-Smadi, [p < 0.05). Some authors have suggested that biological factors such as the influence of female sex hormones and psychological factors including women’s multiple roles as a result of recent societal changes could contribute to these differences between men and women [There were also significant associations with gender and pain severity (l-Smadi,  stated tl-Smadi, ,32. Howend women ,31. NursA study has shown that patients who received information regarding their surgery from their primary physicians reported greater depression levels than those who received the information from nurses ,17,31. TWe suggest that a quick evaluation of anxiety, depression symptoms, and pain as a part of the preoperative workup could enable the identification of high-risk patients for whom pharmacological or nonpharmacological intervention could be instituted. This can be delivered by clinical nurse educators prior to and on admission. Furthermore, many hospitals offer stress management services and these resources could be used for appropriately identified cardiac surgery inpatients. To identify who is most at risk, there are studies that report that age, gender, and marital status can all have an impact on pre-and postoperative anxiety ,29,33.Understanding the associations between pain and psychological distress as well as contributing socio-demographic and medical factors will help to determine which patients are at a higher risk of adverse outcomes. Routine assessments should be performed before surgery to determine patients who are at risk for increased anxiety, depression, and pain after surgery. Nurses should be well trained to evaluate patients’ symptoms of psychological and physical problems. Recognizing all of these symptoms in patients awaiting surgery aids in the planning of appropriate interventions to improve such symptoms that are based on patients’ individual needs or even on health education groups, which helps in preparing the patients for surgical procedures. Further studies should be conducted focusing on the anxiety, depression, or pain of the cardiac patient that is related to the self-management or comparison between the group with and without intervention. The effective result will be determined in further research to improve the quality of life for cardiac patients.Although this study provides several implications for nursing practice, there were some limitations in this study. The cross-sectional nature of this study restricts us from making causal inferences. A longitudinal study could aid in the investigations of the variations in the course of anxiety, depression, and pain associated with CABG surgery. Furthermore, the sources of anxiety were not investigated in this study, limiting the justifications of the results generated. Self-reported measures may include information bias due to the patient’s accurate recall or social desirability. However, investigations based on self-reporting have been proven to be reliable. Another drawback of this study is that the patients may have felt uncomfortable answering the questionnaire prior to CABG surgery, which puts them under additional pressure and stress. They may have given different responses if the questionnaires were completed after the surgery. Because of the limited time available to answer the questionnaire, there may be bias in reporting symptoms. Moreover, convenience sampling and the use of a single tertiary cardiac center can limit generalizability and lead to selection bias. In particular, to reach more accurate conclusions, a larger geographical area taking these predictors into account should be studied.CABG has become a relatively common surgical operation in recent decades. Most of the participants in this study had increased anxiety and depression as well as pain interference levels before surgery. The present study showed that the level of pain is associated with symptoms of depression in patients undergoing CABG surgery. The findings suggest the need for pre and postoperative assessments of psychological symptoms and pain among CABG surgical patients to enhance the patients’ abilities to perform self-care, which in turn can prevent complications. Therefore, intervention is warranted for patients before going through the CABG procedure. Intervening before surgery is crucial since patients who were anxious before the surgery are more likely to have continuous symptoms of anxiety throughout their recovery phase. This requires timely medical interactions and well-thought-out educational programs by nursing professionals to improve treatment outcomes and quality of life. Further studies are required to probe into individual life situations and anxiety of cardiac surgery patients if more effective educational programs are to be devised.


Moreover, the average number of physiotherapy sessions was 2.6 ± 0.6 for the ETMI intervention, while the annual average number in Maccabi is estimated at 4.1 ± 1.5. Three main themes emerged from the thematic analysis: (1) communication between the patient and the practitioner; (2) psychosocial treatment elements, and (3) ETMI as a long-term solution for CLBP. The findings of the current study highlight patients’ perceived need for an open and sincere dialogue and for receiving reassurance and encouragement about their LBP. Notably, they had no problem with the fact that they did not receive passive treatment. Accordingly, together with the significant improvement in post-treatment outcome measures, patients perceived the ETMI method as a practical tool for self-managing their back problems in the long term.This study aimed to evaluate the outcome measures and perceptions of patients with chronic low back pain (CLBP) after being treated with the Enhanced Transtheoretical Model Intervention (ETMI). In this process evaluation mixed-methods study, 30 patients with CLBP electronically completed self-reported measures  before and after ETMI treatment. Subsequently, each patient participated in one-on-one, semi-structured interviews, which were audio-recorded, transcribed, coded, and analyzed thematically. Quantitative analysis showed significant improvements in function ( Low back pain (LBP) is the leading cause of disability worldwide and a significant public health problem, causing a global economic burden . The yeaTo help clinicians overcome those barriers, the Enhanced Transtheoretical Model Intervention (ETMI) was developed, designed specifically to decrease disability among patients with non-specific chronic LBP (CLBP) and to motivate them to increase their engagement in recreational physical activity . ETMI isETMI follows current clinical guidelines and is based on behavior change principles designed to target obstacles to physical activity by addressing self-efficacy and fear avoidance. ETMI consists of a physical examination and a discussion about the role of physical activity, which is matched to the patient’s stage of change and is guided through motivational interviewing techniques, exposure to fast walking, and goal setting. The patient receives a postcard outlining the main messages about physical activity, together with four simple stretches . The intRecent studies address issues around patients’ and physiotherapists (PTs’) perceptions and expectations of current physiotherapy and of the ETMI method ,10. WhilThe use of mixed-methods process evaluation studies in rehabilitation research can enhance the understanding of how psychosocial factors influence LBP ,13,14. AWhile a recent study shows that patients are beginning to perceive ETMI as an evidenced-based model for the treatment of CLBP , there iA total of 30 patients with LBP admitted to a physical therapy consultation in one of Maccabi Healthcare Service (MHS)’s central physiotherapy clinics (Ramat-Gan) in the central district of Israel were enrolled in this study. Recruitment for the study was conducted by the clinics’ administration staff. Inclusion criteria were male and female patients aged 18–55 who were suffering from chronic low back pain (for over 3 months), speak and understand Hebrew, could provide written informed consent, and agreed to take part in a face-to-face interview. Exclusion criteria were dementia or severe cognitive impairments; illnesses or diagnoses that could prevent patients from participating in physiotherapy treatment; patients suffering from neurological conditions or cancer, or those who went through motor vehicle accidents; and pregnant women. The study’s participants were selected using a convenience sampling strategy, relying on age and gender to ensure a representation of varied perspectives . InformeThis mixed-methods study was performed as a preliminary step to conducting a larger prospective cohort study, aimed at investigating the ETMI method’s implementation by the Israeli healthcare services. Qualitative and quantitative data were collected concurrently, and the findings were interpreted in light of identifying inter-relations within the data . The datThe quantitative outcomes included were self-reported function, pain, and fear-avoidance belief ratings. Measurements were performed during patients’ admission and discharge using a customized version of Focus on Patient Inquiry Software for Therapeutic Outcomes (FOTO), Inc., Knoxville, TN, USA ,20. FOTOLCAT scores range on a 0–100 linear scale, with a higher score representing a higher function . The minThe pain was rated with the Numeric Pain Rating Scale (NPRS). In the scale, the patient is asked to rate their pain intensity during the last 24 h on a scale of 0–10 (where 10 = the severest pain). This tool is widely used in the literature and is valid if compared to other pain rating scales. The MCID is 2 points [Fear avoidance was measured using a modified version of the Fear-Avoidance Belief Questionnaire (FABQ) ,26. The As for the qualitative part, a single PT, who was personally qualified, trained, and observed and supervised in the clinical filed by the ETMI’s developer (NBA), was assigned to conduct semi-structured interviews and collect field notes on nuances for the data collection in the physiotherapy clinic. A semi-structured interview guide see  was iterThe semi-structured interview guide was used to elicit participants’ detailed descriptions of their views and experiences of the ETMI method. Interviews were audio-recorded, transcribed verbatim, and coded. Semi-structured interviews and quantitative data collection were conducted until thematic saturation was achieved, the point at which no additional data collection would add to analysis .The ETMI method (detailed elsewhere)  was usedt-test to detect the difference between two dependent means. The input parameters were as follows: for a single-tailed test, assuming a medium effect size of 0.5, α = 0.05, and power = 0.8, the total sample size recommended was 27 participants.The sample size was calculated with G*Power 3.1.9.4 for a paired Quantitative data analysis was performed using IBM SPSS Statistics version 27 . Sociodemographic and outcome scores were described using frequencies, means, and standard deviations (SDs). The Shapiro–Wilk test was used in order to test for normality of the data. In order to explore the differences before and after the intervention, we used a paired t-test for normally distributed variables and Wilcoxon signed-rank test for non-normally distributed variables. Correspondingly, effect sizes were calculated using Cohen’s d and Pearson’s r . AdditioThe qualitative analysis was based on a thematic analysis of the interviews. Following Brown and Clarke’s  six-stepMixed-methods analysis began by integrating individual participants’ quantitative measures and exemplar quotes into a joint display. A joint display is a recommended tool for mixed methods in order to facilitate the interpretation and understanding of relationships among data . Next, pAll the 30 patients enrolled in this study completed the intervention. A description of the patients’ characteristics are presented in An average of 2.6 ± 0.6 physiotherapy treatment sessions were administered during the ETMI intervention . ComparaA summary of the quantitative analysis is presented in p < 0.001) between the functional score measured at admission  and the functional score measured at discharge , with a large effect size [p < 0.001, with a large effect size—Cohen’s d = 1.234.The Shapiro–Wilk test indicated that all variables representing function were normally distributed. The paired sample t-test revealed a positive significant change (t(29)= 11.42, ect size —Cohen’s p < 0.001.The Shapiro–Wilk test indicated that pain ratings at admission were normally distributed; however, the normality assumption was denied for pain levels at discharge. A Wilcoxon signed-ranks test indicated that pain at discharge (median = 6) was lower than pain at admission (median = 1.5); z = −4.8, p < 0.001).The exact McNamar’s test revealed a statistically significant reduction in fear-avoidance beliefs post-intervention compared to pre-intervention  comA coding scheme with quotations underpinning the variety of the sub-themes is provided in Most patients noted that one of the most significant things that they experienced during the first treatment was the therapist’s attentiveness to their problems. Patients noted that it was important for them to have someone who was attentively listening to their problems, without interrupting them.Furthermore, all patients emphasized the importance of the initial dialogue between the practitioner and the patient during the first session. They all mentioned the importance of having an open and sincere dialogue, as it enables the patient to take an active part in the process. They stated that it made them feel like they were taking part in their healing process. Most of them maintained that it was the first time they experienced an open dialogue with a practitioner.All patients stated that they received an in-depth explanation as a result of the dialogue, which, in turn, helped them to obtain a wider perspective of their health problem.Most patients noted that, throughout the treatments, they felt that they gained a great deal of self-confidence in handling their back problem, together with a sense of reassurance, which was given by the practitioner. Most stated that they felt much more calmer and reassured regarding their back pain as the treatments progressed.Some patients mentioned that their sense of fear, specifically the fear of pain and causing damage to their back, diminished throughout the treatments.Finally, most patients noted that their sense of empowerment and self-efficacy in returning to normal while performing their daily routine increased significantly during the treatments.Most patients agreed that the treatment they underwent gave them some practical tools to self-manage their back problem in the future. Among other things, most patients maintained that they adapted to a healthier lifestyle, with an emphasis on regular and daily exercise, in order to avoid, as much as possible, future back pain. In addition, they noted that the tools they received during the treatments provided them with the information they were missing and that, currently, they are able to self-manage their back problem in a much better way than before.All patients gave their insights into the treatment they experienced. All the insights were positive and referred to their better understanding of their LBPdue to the treatment. Patients indicated their understanding that they could return to their daily function and activities, even though their back pain was not completely resolved.This study focused on the perceptions and outcome measures of patients with CLBP following physiotherapy treatment using the ETMI method. By using mix-methods research, this study obtained a more comprehensive view of patients’ treatment perceptions, relationships with clinicians, and lived experience of their problems following physiotherapy treatment using the ETMI method ,36.Patients who were treated with the ETMI method not only demonstrated significant improvement in their outcome measures but also perceived ETMI as a positive and applicable method to treat their back problem.The qualitative analysis indicated that patients perceived the ETMI method as a practical tool for self-managing their back problems for the long term. Specifically, patients’ perceived the need for an open and sincere patient–practitioner dialogue and for receiving reassurance and encouragement about their back pain. Patients also indicated that treatment using the ETMI method helped them regain their self-confidence and self-efficacy to overcome their pain.Notably, patients did not have any problem not receiving passive treatment as part of their physiotherapy session.Our findings are consistent with those of studies that indicate that patients seek a confidence-based relationship with their caregivers ,11,37,38p < 0.001), with large effect sizes where applicable. Notably, a large effect size was recorded between the post-treatment LCAT’s risk-adjusted predicted functional score and the functional score measured at discharge. These data indicated that the change in the functional score was not only significant between the admission and discharged scores but also significantly better than the improvement predicted by the FOTO logarithm. Furthermore, the quantitative analysis demonstrated a significant reduction in fear avoidance among all patients. Of the 17 patients previously categorized as having high fear avoidance, all moved to the low category. This, in fact, reinforces the results of previous studies on ETMI that have shown that ETMI is effective in reducing disability and pain and improving self-reported outcome measures, e.g., mental and physical health [The quantitative analysis demonstrated significant changes in all outcome measures  and patient treatment perceptions.


Direct stimulation of the afferent nerve endings in the venous endothelium is one explanation of propofol injection pain. Previous studies found that ondansetron can also block sodium channels. This effect is similar to that of lidocaine.The primary outcome was the efficacy of ondansetron compared to lidocaine and placebo for the reduction of propofol injection pain.This trial was conducted in 240 patients, American Society of Anesthesiologists classification I-III and aged between 18–65 years old, undergoing elective surgery, and having a 20-gauge intravenous catheter at the hand dorsum. Each group of 80 patients received 8 mg. of ondansetron in the O Group, 40 mg. of lidocaine in the L Group and normal saline in the C Group. The study medications were blindly administered to the patients through a 20-gauge intravenous catheter placed on the hand dorsum, and then 1 min later, the small dose of propofol (50 mg.) was infused via the syringe pump at a rate of 600 ml/hr. for 30 s. Following that, the syringe pump of propofol was temporarily stopped, and the patients were asked to rate their pain at the injection site.P < 0.01). The median pain score in the L, O, and C groups were 2 (0–4), 4 (2–5), and 4.5 (2–6), respectively (P < 0.01). The incidences of no pain, mild, moderate, and severe pain were also significantly different in the L group  compared with those in the O group  and the C groups  (P < 0.01).The incidence of pain was lowest in the L group (66.2%) compared with the O (82.5%) and the C groups (85.0%) (Pretreatment with intravenous lidocaine, rather than ondansetron, can reduce the incidence and intensity of propofol-induced pain. However, injection pain is common and causes patients discomfort during the induction of general anesthesia. The incidence of injection pain has been shown to vary between 28 and 90% [thof 33 clinical anesthesia dissatisfaction outcomes [Propofol is the most commonly used intravenous anesthetic drug and 90%  and the Ondansetron is a specific serotonin 5-HT3) antagonist. Previous studies found that ondansetron can block sodium channels  and opio-HT3 antaIn this study, we compared the efficacy of 8 mg. ondansetron to 40 mg. lidocaine and a placebo for the reduction of propofol injection pain as the primary outcome. The secondary objective was to compare the incidences of postoperative nausea and vomiting in each group.www.clinicaltrails.in.th) on July 20, 2019 . After all of the patients were informed about the study and signed the informed consents, we recruited 240 patients of both genders, American Society Anesthesiologists physical (ASA) status I–III and aged between 18–65 years old, undergoing elective surgeries under general anesthesia in Songklanagarind Hospital, Thailand between August 2019 to November 2020. All of them were inserted with the intravenous catheter number 20-gauge at the hand dorsum prior to surgery.This double-blinded randomized controlled trial was conducted after approval by the Ethics Committee of the Faculty of Medicine, Prince of Songkla University (REC.62–107-8–1) in accordance with the Declaration of Helsinki(1964). It was prospectively registered in the Thai Clinical Trial Registry , 40 mg. of lidocaine (Group L) or 0.9% sodium chloride solution (Group C). The random lists were concealed in the envelopes. The random code number was notified for the preparation of total volume of 4 mL. of colorless medications in the 5 mL.-syringe on the morning of the day of surgery by the anesthetist who was not involved in either the administration of study medication or the assessment of the patients. No premedication was administered and the current analgesic drugs were discontinued. A 20-gauge intravenous catheter was inserted into the superficial vein on the hand dorsum and the patients received intravenous fluid infusion on the morning of the day of surgery.At the operating room, demographic data was recorded by the nurse anesthetists. The leaked, improper placement or dislodgment of the intravenous catheter was checked before the start of induction. All patients were pre-oxygenated with 100% oxygen which was delivered through a facial mask. The study medications were given to the patients through a 20-gauge intravenous catheter placed on the hand dorsum, then 1 min. later, the small dose of propofol (50 mg.) was infused via the syringe pump at a rate of 600 ml/hr. for 30 s. Following that, the syringe pump of propofol was temporarily stopped, and the patients were asked to rate his/her pain at the injection site using a verbal numerical rating score (VNRS) in which score 0 is no pain and score 10 is the worst pain. The residual dosage of propofol was then injected, followed by opioids and neuromuscular blocking agents. Systolic and diastolic blood pressures, heart rates, oxygen saturation, electrocardiogram were monitored and recorded during induction and after intubation. Post-operative nausea and vomiting (PONV) was evaluated at the post anesthetic care unit.% drop out.The definite number of the population was then 47 patients in each group. Moreover, the sample size calculation to cover secondary outcome (PONV) was also used the same formula with data from a previous study [% drop out, the final size of the population was 80 patients in each group.The sample size was calculated with the two-independent proportions formula (two-tailed test) from the propofol pain injection incidence in Songklanagarind Hospital . To reduus study . To reduStatistical analysis was performed using Rstudio 1.3.1056. Continuous variables were presented as mean and standard deviation (SD) or median and interquartile range (IQR). Categorical variables were presented as the number of patients and percentages. Continuous variables were analyzed by ANOVA F- test, Kruskal–Wallis test or pairwise Wilcoxon test. Categorical variables were analyzed by Fisher's exact test or Chi-square test. P-value less than 0.01 was considered as statistical significance. The power of this study was 0.8.Three hundred and eighty-four patients were assessed for eligibility from August 2019 to May 2020. One hundred and forty-four patients were excluded and two hundred and forty patients were randomized and then allocated into each group.  and the C groups (85.0%) (P = 0.01).  and in the C groups  (P < 0.01). (Table P < 0.01)  compared with the O group (82.5%) , which produces local vasodilatation and increased vascular permeability. In consequence, there is increased contact between propofol and free nerve endings . A meta-The factors that are associated with propofol injection pain include the size of the intravenous catheter, site of injection, speed of injection, and lipid solvent of propofol . These cThere were no significant differences between the incidences of postoperative nausea and vomiting among the three groups. This may be due to the wide variation in the surgical duration. Even the 8 mg. of ondansetron is an adequate dose to prevent postoperative nausea and vomiting. However, the time of administration is also important. The surgical duration in our study commonly lasted 4 h., longer than the effective duration of ondansetron which should be within 4 h. The effective antiemetic property of ondansetron usually occur within 30 min. after administration, so it is, therefore, better to administer ondansetron before the end of the operation. One of the lethal adverse effects of ondansetron is prolonged QT which can produce significant arrhythmias. Nevertheless, there was no patient with prolonged QT or arrhythmia in our study.The limitation of this study was the administration of a sub-hypnotic dose of propofol before pain assessment. Therefore, a reliable pain assessment can be confusing.Pretreatment with 8 mg. of intravenous ondansetron before induction did not significantly reduce the incidence and intensity of propofol-induced pain compared to the pretreatment with 40 mg. of intravenous lidocaine. There was either no advantage of prevention of post-operative nausea and vomiting.


During the period of the study, 61.1% of the patients showed symptoms of allergy, with 77.27% of them having tested positive for sIgE. The total IgE level was elevated in 18.06% of the patients and correlated with clinical symptoms of allergy (p = 0.004). An elevated total IgE level was not observed in children receiving immunoglobulin replacement therapy. Conclusion: The study showed that serum sIgE and total IgE together might be a plausible diagnostic tool for PID patients. However, for patients receiving immunoglobulin replacement therapy, the assessment of total IgE is not useful.Background: Allergy is a clinical condition that reflects a deviated function of the immune system. The purpose of this study was to evaluate serum allergen-specific IgE (sIgE) along with clinical manifestations of allergy in patients with diagnosed primary immunodeficiency (PID). Methods: 72 patients, aged 1–17 years, diagnosed with PID and hospitalized between July 2020 and February 2021 were included in the study. Blood samples were obtained by venipuncture. sIgE , blood eosinophil count, as well as total IgE and IgG were measured and assessed in relation to a detailed medical examination. Results: Serum sIgE was detected in the blood of 50% of the patients in the study group, which significantly correlated ( Inborn errors of immunity (IEI) are a heterogeneous group of inherited diseases associated with genetic susceptibility, often stemming from a single-gene mutation. In the past, their prevalence was estimated at approximately 1:10,000–1:50,000. Due to novel diagnostic procedures, new nosologic units have been described and classified as primary immunodeficiencies (PID). The description of clinical phenotypes is being continuously updated . CurrentAllergy develops due to a deviated function of the immune system. The occurrence of allergy in the context of PID has always been a compelling issue. Several PIDs are frequently associated with allergies. Moreover, common allergic reactions  are exaggerated immune responses that may be manifestations of an underlying PID . AppreciAtopic dermatitis (AD), in association with an elevated level of total IgE, constitutes a clinical feature of the hyper-IgE syndrome, Omenn syndrome, and Netherton syndrome. In the Wiskott–Aldrich syndrome (WAS), features of eczema are indistinguishable from those of atopic eczema. Selective IgA deficiency (sIgAD) often coexists with asthma, allergic rhinitis (AR), AD, and food allergy (FA) ,10. AlleStudies on the prevalence of allergy in several PID disorders have shown mixed results. The reported differences might be due to differences in methodological approaches, as well as to ethnic and geographical diversity ,13. ThusThe study was consented by the Bioethical Commission of the Wroclaw Medical University. Patients included in the study were previously diagnosed with PID (according to IUIS criteria and classification and ICD-10) and hospitalized in the Clinical Immunology and Pediatric Ward of the J. Gromkowski Provincial Hospital in Wroclaw from July 2020 to February 2021. All parents/legal guardians and patients over 16 years signed an informed consent before inclusion in the study.n = 46 boys, n = 26 girls) aged 1–17 years . The baseline characteristics of the patients are presented in n = 51; 70.83%) constituted most of the study group, followed by patients with combined immunodeficiencies associated with syndromic features . In addition, the study group was divided into two groups depending on the treatment received: a group of patients received permanent immunoglobulin (Ig) substitution therapy , and a group did not receive Ig substitution therapy  at the time of the study. The group of patients receiving Ig replacement therapy (IRT) included patients with X-linked agammaglobulinemia (n = 1), common variable immunodeficiency , IgG subclass deficiency (n = 1), four patients with other hypogammaglobulinemias such as IgG deficiency (n = 3) and IgG subclass plus IgM deficiency (n = 1), one patient with Kabuki syndrome plus IgG subclass deficiency, one patient with PRKDC mutation with IgG subclass deficiency, two patients with severe combined immunodeficiency , and the other was enrolled four years after HSCT), three patients with Nijmegen breakage syndrome (NBS), three patients with ataxia–telangiectasia (A-T). Doses of Ig were individualized and were within 0.2–0.8 g/kg  a documented diagnosis of allergic disease performed by a trained allergist/pulmonologist, (2) family history of allergic diseases, (3) recurrent respiratory tract infections, (4) skin eczema, (5) medications taken, especially antihistamine drugs, (6) weight and/or height deficiency, (7) place of residence .Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat epithelia, horse epithelia, dog epithelia, Cladosporium herbarum, Aspergillus fumigatus, Alternaria alternata; (3) IgG concentration; (4) blood eosinophilia; (5) total IgE level.The following parameters were assessed by venous blood analysis: (1) concentration of sIgE against 18 food allergens: egg white, egg yolk, cow’s milk, alpha-lactalbumin, beta-lactoglobulin, casein, bovine serum albumin (BSA), codfish, flour mix, rice, soybean, peanut, hazelnut, carrot, potato, apple, cacao, chicken; (2) concentration of sIgE against 11 inhalant allergens: 6 grass mix, birch pollen, mugwort pollen, Clinical symptoms were assessed by a questionnaire including questions on inhalant allergy: sneezing, rhinorrhea, nose/eyes itching, need to rub nose/eyes, watery eyes, nasal obstruction, with or without facial itching, nasal congestion, reduced sense of smell, trouble breathing with mouth closed. Symptoms of IgE-mediated food allergy  were assessed separately. Assessment of asthma and atopic dermatitis was mainly based on specialists’ consultations obtained from medical documentation.® test , according to the manufacturer’s instructions. The threshold for a positive result for sIgE, which was indicative of sensitization, was ≥0.35 kUa/L. Subjects with at least one positive sIgE were considered to be sensitized. IgG and total IgE concentrations were measured by immunoturbidimetry. The total IgG and IgE reference ranges depended on the age of the individual. Elevated total IgE was defined as total IgE concentration above the age-related reference ranges.sIgE were measured by quantitative enzyme immunoassay—the Polycheck p-value less than 0.05 was considered statistically significant.Statistical analysis of the data was conducted using the spreadsheet of Microsoft Office Excel  and Statistica v.13—for qualitative data—Pearson’s chi-squared. The significance level was accepted as α = 0,05. A n = 36) of the PID patients (n = 72), which correlated (p < 0.0001) with the presence of clinical symptoms of inhalant and/or food allergy (n = 44) of the children with PID reported subjective symptoms of allergy, and in this group, 77.27% (n = 34) tested positive for sIgE. In most cases, there was a correlation between reported symptoms and positive sIgE. In 17 patients, the correlation was more evident, notably if there were symptoms of inhalant allergy (n = 12).sIgE ≥ 0.35 kUa/L were detected in the sera of 50.0%  ranged from 0.35 to 3.5 kU/L, while in 22.22% (n = 16) of the patients, sIgE concentration was ≥3.5 kU/L (n = 16) of the PID patients, while in 18.06% (n = 13), sIgE against three and more allergens were observed. In most cases, sIgE were against food allergens , whereas in 9 children (12.5%), they were only against inhalant allergens, and in other 9 children (12.5%) they were against both inhalant and food allergens.sIgE concentrations in the majority of allergic patients (3.5 kU/L . sIgE agn = 24) of patients with PID was an interesting finding. In most of these cases , it correlated with clinical symptoms of milk allergy at the time of the study or in the past. sIgE against BSA showed low values . A higher concentration of sIgE against BSA was observed in patients without Ig replacement therapy than in patients receiving Ig substitution therapy, and the difference between these two groups was statistically significant  against BSA in 33.33% (n = 16) had a significantly increased sIgE level (p = 0.003).Twenty-one (29.17%) patients showed chronic or recurrent skin eczema, and the majority of them (p = 0.55).There was no significant correlation between the prevalence of recurrent respiratory tract infections and the serum sIgE level (p = 0.0002). However, no correlation with blood eosinophilia (p = 0.85), recurrent respiratory tract infections (p = 0.23), family history of allergic diseases (p = 0.99) was observed. There was no significant difference between males and females (p = 0.39).The levels of sIgE against inhalant allergens correlated with an elevated total IgE (p = 0.31), total IgE (p = 0.14), weight deficiency (p = 0.87), height deficiency (p = 0.65), positive family history of allergy (p = 0.53). There was no effect of the treatment with antihistamine medications (p = 0.54).The levels of sIgE against food allergens did not correlate with eosinophilia (n = 26) of the patients with increased sIgE were males, the difference between the sexes was not significant (p = 0.14). In addition, there was no significant difference between different groups of PID (Although 72.22% (s of PID .p = 0.42).An increased sIgE level was observed in 47.17% (25/53) of patients not receiving IRT and in 57.89% (11/19) of patients undergoing IRT, but the difference between these two groups was not statistically significant (p = 0.047) was observed with regard to rural or urban residence  of the 36 children with increased (≥0.35 kU/L) sIgE. On the other hand, 84.62% (n = 11) of the 13 patients  with an elevated total IgE level had increased sIgE concentration as well. There was a statistically significant correlation between sIgE and total IgE levels (p = 0.014). Furthermore, an elevated level of total IgE correlated with clinical symptoms of allergy in this particular group .The total IgE level was normal in the majority  between PID patients treated with Ig and PID patients who were not undergoing Ig therapy (n = 13) of patients not receiving IRT, such deviation was not observed in those patients (n = 0) who were undergoing IRT.There was a statistically significant difference ( therapy . While tn = 11) of the 72 patients included in the study. Eosinophilia was slightly more often observed in females  than in males , but the difference was not statistically significant (p = 0.48). The counts of eosinophils did not correlate with sIgE presence (p = 0.74), clinical symptoms of allergy (p = 0.62), skin eczema (p = 0.85), recurrent respiratory tract infections (p = 0.29), or total IgE level (p = 0.66).Increased counts of eosinophils were observed in the blood of 15.28% , who show extremely low levels of IgE, traditional methods of sIgE measurement may provide false-negative results. In such conditions, sensitization should be confirmed using other methods, for example, bronchial provocation tests with allergens, etc. . In a stn = 20) of the patients with PID, while 22.22% (n = 16) of the study group had an sIgE level above 3.5 kU/L. Nevertheless, we are aware that the utility of, especially, food-specific IgE concentrations in predicting symptomatic food allergies in the context of IEI patients may be questionable, and further studies including, e.g., oral food challenges are needed. Defining the cut-off values for specific IgE among patients with immunodeficiency would be helpful in clinical practice.According to some studies, the cut-off level of 0.35 kUa/L for allergen-specific IgE might be insufficient to predict clinical reactivity ,20,21,22Allergy tests, both skin testing and in vitro sIgE tests, must always be interpreted in the context of the patient’s specific clinical history, because a “positive” test does not always entail clinical allergy ,24,25. TThe likelihood that a positive sIgE test result will correlate with clinical symptoms is influenced by the degree of positivity, the type of allergen, and the patient’s clinical history. Venom- and food-specific IgE have been reported in up to 25% and 60% of the general population, respectively ,27,28. In = 20) involving one or more main classes of immunoglobulins as well as patients with IgG subclass deficiency (n = 20) constituted the majority of the study group. The prevalence of sIgE and clinical symptoms of allergy varied between the types of PID . However, the authors indicated that FA was more commonly reported in patients with specific PIDs, compared to what would be expected in the general population, i.e., in the presence of combined immunodeficiencies (33.3%), sIgAD (25%), CD40 ligand deficiency (7.7%), primary hypogammaglobulinemia (7.1%), hyper IgE syndrome (6.3%) . AD was Although the problem of the coexistence of allergy and PID diseases has been a subject of investigation in a number of studies, the results are largely inconsistent. While in an Iranian study involving patients with sIgAD, atopic eczema was observed in 52% of the patients , in BrazIn the group of patients with PID, differences with regard to the place of residence and an increased prevalence of allergy in patients residing in urban areas were observed, which mirrors the results of epidemiological studies involving the general population . This isThe fact that the values of the total IgE level were normal in PID patients undergoing IRT is an interesting observation that is confirmed by some other studies ,37. Duran = 10). Two patients from that group were receiving Ig replacement therapy at a stable dose during the entire study, two had an sIgE concentration between 0.15 kU/L and 0.35 kU/L against cat dander, and another two against birch pollen with airway allergic symptoms. The possibility of non-IgE-mediated mechanisms remains to be investigated.Another point to be addressed regards patients with reported symptoms of allergy without positive (≥0.35 kU/L) sIgE (The main limitations of this study was the use of a single method for confirming patients’ sensitization, without provocation tests and assessment of asthma phenotypes. These issues will be addressed in follow-up studies.In IEI, an abnormally functioning immune system often does not protect the organism from infections and permits abnormal and excessive hypersensitivity reactions. The development of allergies in IEI is caused by the disruption of the complex balance between effector and regulatory cells in the immune system . The potThis study revealed that the prevalence of allergic diseases and atopy in the pediatric population with IEI is high. PID patients should be carefully monitored with regard to their risk of allergy. The study showed that serum sIgE and total IgE together might be a plausible diagnostic tool for these patients. However, for patients with IRT, the assessment of total IgE is not useful in the context of allergy. Further, more detailed studies including patients with increased levels of sIgE are needed.