No relevant differences in the other parameters examined were found. Conclusion: Patients with lung cancer have their own peculiarities, including higher basal and BTcP pain intensity and the use of more adjuvant drugs for background pain. The most frequent triggers for predictable BTcP are movement and cough. Future studies should be performed to analyze the prevalence of BTcP in patients with different lung cancers as well as the optimal management strategy for background pain and BTcP. Aim: To characterize breakthrough cancer pain (BTcP) in patients with lung cancer. Methods: This was a secondary analysis of multicenter study of patients with BTcP. Background pain intensity and opioid dose were recorded. The number of BTcP episodes, their intensity, predictability, onset, duration and interference with daily activities were collected. Opioids used for BTcP, the mean time to meaningful pain relief after taking medication, satisfaction and adverse effects were assessed. Results: 1087 patients with lung cancer were examined. In comparison with other tumors, patients with lung cancer showed: higher background pain intensity ( Lung cancer is the most important cause of cancer-related death in the world. In 2016, about 220,000 new diagnoses of lung cancer were reported and about 150,000 of patients died for the disease. For every 100,000 people, 56 new cases were diagnosed and 39 died. Despite the improvement in diagnosis and treatment, this population has a poor prognosis. About 59% have a 5-year survival after diagnosis and more than 5,000,000 of patients are alive in the United States [The majority of patients with lung cancer experience burdensome symptoms associated to disease or treatments, which particularly occur in the advanced stage of their illness. Pain is one of the most distressing symptoms because of its debilitating effects, which produce depression and anxiety . Patients with lung cancer develop complex and variable clinical conditions, depending on previous anticancer treatment received and the extension of disease. Pain if often a direct consequence of the malignancy and multifactorial in origin, so that patients may experience pain in different anatomical sites. Anticancer treatments may cause important pain syndromes, as it occurs after surgery or radiotherapy. Chest wall and vertebral bones are the most frequent sites of pain localization, although numerous syndromes have been identified .About 90% of patients with lung cancer experience pain in the advanced stage of disease ,6. Pain Cancer pain management is difficult and may sub-optimal in many circumstances. Different factors, including poor pain assessment, inadequate knowledge and sub-optimal prescription of analgesics and poor capabilities to manage opioid adverse-effects may result in an undertreatment .Other than background pain, reported most hours of the day, cancer patients may experience peaks of pain intensity . This tyIndeed, data regarding the BTcP in patients with lung cancer is lacking. The primary outcome of this study was to assess BTcP characteristics in patients with lung in comparison with those of patients with other primary tumors. The secondary outcome was to assess the management of background pain and BTcP, patients’ satisfaction with medications used for BTcP and adverse effects associated with the use of drugs for BTcP.This was a secondary analysis of a large, multicenter, national study of BTcP. Thirty-two centers were involved . The locAge, gender and Karnofsky level were recorded. Average pain intensity  and analgesics prescribed for background pain and their doses   were recThe characteristics of BTcP were collected—number and intensity , of BTcP episodes, predictability and triggering factors, BTcP onset , duration of untreated BTcP episodes, the interference with daily life . BTcP medications, the mean time to meaningful pain relief after receiving the medication and satisfaction with BTcP pharmacological treatment , were assessed. Adverse effects specifically attributed to BTcP medications were recorded. p > 0.05). Lung cancer association patterns has been assessed using χ2 tests using personal, pain characteristics, BTcP, pain and BTcP medications. Independent t-tests for comparing groups have been performed where due, adjusting the degrees of freedom with the Satterthwaite correction to account for heteroscedasticity. Statistical software STATA  was used for the statistical analysis.Descriptive statistics for patients’ characteristics, basal pain and BTcP have been reported providing mean values and frequencies stratified by Lung cancer occurrence. Groups profiles, affected or not affected by lung cancer, have been compared, carrying out a multivariate Hotelling T2 test (α = 0.05). Post-hoc analysis performed pairwise comparisons Bonferroni’s adjusted for familywise error. Gender and age have been checked for confounding. A logistic regression provided different probabilities of Lung cancer occurrence conditioning on gender accordingly. Age was not statistically significant (p = 0.005). Of the 4016 patients recruited in the original study, one-thousand-eighty-seven patients had lung cancer. The characteristics of patients with lung cancer and other tumors are described in p = 0.006). The mean OME was 65.9 mg/day. This dosage was lower than that reported in patients with other tumors .One thousand fifty-nine (97.4%) and 924 (85.0%) patients were prescribed opioids for background pain and for BTcP, respectively. The mean background pain intensity was 3.1 (Standard Deviation 1.78), which was higher than the pain intensity found in other tumors (p = 0.104).Patients with lung cancer reported a mean number of BTcP episodes of 2.4/day . No differences in comparison with other primary tumors were found (p = 0.005) was found. The mean duration of an untreated BTcP episodes was 40.9 min (SD = 32.59). No statistical differences with other tumors were found (p = 0.174). The mean intensity of BTcP episodes was 7.6 (SD 1.27). A statistical difference with other tumors . The main trigger of predictable BTcP was the movement (79.5%). Cough, ingestion of food, procedures and other causes were the other triggers . When compared to other tumors, patients with lung cancer were more likely to have predictable BTcP with movement (79.5% vs. 57.7%) and cough (8.2% vs. 1.5%) and less likely to experience predictable BTcP related to ingestion of food  and procedures (5.6% vs 6.0%) (p = 0.0001).BTcP was predictable in 343 patients (31.5%). No statistical difference with other tumors was found (p = 0.099).A short onset BTcP (≤10 min) was found in 771 patients (70.9%), while in 316 patients (29.1%) BTcP onset was longer (>10 min). No differences with other tumors were found (p = 0.711)The mean time to meaningful pain relief after receiving a BTcP medication was 16.3 min (SD 14.52). No statistical differences with other tumors were found (p = 0.009).BTcP interference with daily activity was mild, much and very much in 117 (10.9%), 653 (61.0%) and 297 (27.8%) patients, respectively. Statistical differences were found in comparison with other tumors, 14.7%, 56.2% and 28.8%, respectively , paracetamol ; weak opioids ; oral morphine , oral hydromorphone , oxycodone ; oxycodone/naloxone , tapentadol , parenteral morphine , methadone , transdermal fentanyl , transdermal buprenorphine . Eight-hundred-twelve patients (76.2%) were prescribed adjuvant drugs, including benzodiazepines , anticonvulsants , antidepressants , antiemetics , laxatives  and corticosteroids .p = 0.0001)—antiepileptics (35.7% vs. 28.7% p = 0.0001), antidepressants (11.3% vs. 8.7% p = 0.011) and corticosteroids (45.1% vs. 34.6% p = 0.0001) and less frequently antiemetics (5.9% vs. 10.2% p = 0.000) and benzodiazepines .Patients with lung cancer more frequently used adjuvants . Patients with lung cancer were more frequently prescribed anti-inflammatory drugs . No differences in the meaningful pain relief after BTcP medications were found .No differences in BTcP medication was found, unless for parenteral morphine which was less frequently used in patients with lung cancer (p = 0.846). Thirteen patients reported adverse effects of mild intensity. No adverse effects of moderate or severe intensity were reported.Adverse effects due to BTcP medications were reported in 13 patients (2.5%). No differences with other tumors (2.7%) were found (The majority of lung cancer patients were satisfied or much satisfied with BTcP medication (641 (61.5%) and 89 (8.5%), respectively). No differences with other primary tumors were found.The large sample of patients analyzed in this study allowed us to gather relevant information regarding the phenomenon of BTcP in patients with lung cancer. In comparison with patients with other tumors, patients with lung cancer had higher levels of background pain, while receiving lower opioid doses and more adjuvant drugs and anti-inflammatory drugs. BTcP intensity was higher in patients with lung cancer and resulted in a larger interference with daily activities. The main causes of predictable BTcP were movement and cough, suggesting some peculiarities of this population in comparison with population affected by other primary tumors. All these findings suggest that clinicians resort to other drugs to improve opioid analgesia, rather than increasing the doses of opioids, as pain would be less responsive to opioid drugs . The useComparative data regarding BTcP in patients with lung cancer are limited. In a pioneer study performed in home care patients with lung cancer, somatic incident pain, which is a subtype of BTcP principally attributable to bone metastases, resulted to be a negative prognostic factor for pain control , as it oThere are some limitations of this study, as it was a secondary analysis of an original study performed in patients with a diagnosis of BTcP, according to a predetermined algorithm. Thus, the prevalence of BTcP in patients with lung cancer remains unknown. In a sample of advanced cancer outpatients with a prevalent diagnosis of lung cancer, the prevalence of BTcP was about 40% . MoreovePatients with lung cancer have their own peculiarities, including higher basal and BTcP pain intensity and the more frequent use of adjuvant drugs for background pain. The most frequent triggers for predictable BTcP are movement and cough. The implication of the present findings is that patients with lung cancer have their own peculiarities in BTcP presentation. This knowledge may help clinicians provide the best management. Future studies should analyze the prevalence of BTcP in patients with different lung cancers as well as the optimal analgesic strategies for background pain and BTcP.


The purpose of this qualitative study was the assessment of the feasibility and acceptance of orthopedists prescribing individualized therapeutic exercises via a smartphone app to patients suffering from non-specific back pain.A total of 27 patients (mean age 44.8 ± 13.2 years) diagnosed with acute non-specific back pain were prescribed individually chosen therapy exercises via a smartphone app. Before the patients started and after 4 weeks of exercising all participants went through an assessment protocol consisting of questionnaires , assessment of functional parameters . With 16 randomly chosen patients semi-structured interviews were undertaken at the end of the intervention period. Interview transcripts were analyzed using thematic analysis. Power analysis and a priori sample size calculations were undertaken with the quantitative data.From the interviews four thematic categories emerged: prior exercise experience, evaluation of exercise intensity, communication with physician via smartphone app, and variability of exercise location. Quantitative analysis of secondary data showed significant improvements in back pain (ODI) as well as quality of life domains “physical functioning”, “bodily pain” and “vitality” (SF-36) of which “bodily pain” was sufficiently powered with the current sample size.The prescription of therapeutic exercises via smartphone app to patients suffering from non-specific back pain is feasible and well-accepted in patients at all ages. Pilot data additionally pointed towards efficacy of the intervention. Approximately two thirds of all adults suffer from back pain at least once in their lifetime. Of these, only 15% are diagnosed with a specific structural damage of the spine while the rest are classified as suffering from non-specific back pain , 3. It hPatients with back pain who routinely presented at four orthopedic specialist offices located all over Vienna, Austria, and were diagnosed with non-specific back pain were considered eligible for study inclusion. Further inclusion criteria were age between 18 and 69 years, possession of a smartphone, willingness and ability to perform therapeutic exercises following visual and verbal introductions as well as sufficient knowledge of the German language to understand the instructions. Exclusion criteria were any physiological or mental disease which would impair the ability to perform therapeutic exercises, already planned start of an exercise therapy during the intervention period and pregnancy. Sociodemographic characteristics are depicted in Table After obtaining written consent, the patients were sent to the Department of Physical Medicine, Rehabilitation and Occupational Medicine of the Medical University of Vienna, Austria, for baseline testing within 1 week after the initial doctor’s visit. After completion of the baseline tests therapeutic exercises which were individually chosen by the treating orthopedist were unlocked for the patients in the respective smartphone app. The patients were now encouraged to perform these exercises independently for 4 weeks and then come back for a follow-up test.The analysis of the main outcomes, the feasibility and acceptance of the smartphone app, was undertaken via semi-structured interviews following standard guidelines for qualitative research . The intQuantitative data collection consisted of functional assessments , assessment of back pain (Oswestry Disability Index (ODI); visual analogue scale (VAS)), quality of life (SF-12), physical activity , work ability (work ability index short form), as well as sociodemographic parameters.The smartphone app which was utilized in this study was developed with the aim not just to provide exercise videos but to be a communication tool between patients and doctors. It was approved as a class 1 medical device by the Austrian Agency for Health and Food Safety (AGES) and registered in the Austrian Medical Devices Registry. The utilized version contained the videos of 48 therapeutic exercises. For each exercise there was one introduction video provided and one to go along while exercising. Depending on the input of the diagnosis based on the Austrian guidelines for acute and chronic non-specific back pain  by the tData were analyzed using thematic analysis, which involved several steps : the firReading of the transcripts was undertaken by two independently working researchers (TH and TW) with the aim to broaden data interpretation. Moreover, this allowed further insight into the emerging themes. The analysis offered is one interpretation of the interviewees’ experiences and it has to be noted that other interpretations are possible. Nevertheless, as the aim was offering a credible and trustworthy interpretation which collects participants’ perceptions and experiences, ‘thick description’ is provided via the use of direct quotations to give the readers the opportunity to evaluate the interpretation themselves.Quantitative data were compared between baseline and follow-up measurements via dependent t‑tests . Post hoc power analysis was calculated with G*Power (Version 3.1.9.4) . Based oThis study was approved by the ethics committee of the Medical University of Vienna (EK 2233/2017) as well as the ethics committee of the City of Vienna (EK 18-095-0618) and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. All participants gave their informed consent prior to inclusion in the study.A total of 32 patients were included in this study, of whom 27 completed the full study procedure and all measurements. Of the five drop-outs, one patient at the baseline measurement turned out to have been diagnosed with a structural damage of the spine before and was therefore treated as a screening error, one patient was diagnosed with a structural damage of the spine during the test phase unrelated to the exercises, one patient was hospitalized during the test phase due to an unrelated disease, and two patients lost interest to participate in this study, one between screening and baseline measurements and one during the test phase. Patient flow and respective drop-out reasons are depicted in Fig. During the thematic analysis four categories were identified: prior exercise experience, valuation of exercise intensity, communication with physician via smartphone app and variability of exercise location.Pseudonyms are used throughout the manuscript.Patients who were physically active before or were experienced in (back-specific) physical exercises realized this when exercising with the app. They did ot have any problems performing the exercises. Some patients mentioned that prior physical exercise gave them some kind of motor reference value they could use to assess if they performed the current exercises correctly: “I think it’s better to have exercise experience. If someone does not have any exercise experience at all, it will become difficult.” . Another patient who reported performing group exercises twice per week phrased it as follows: “Sometimes I was a little bit insecure. But then there was my group exercise which I attend twice per week where I am supervised and getting my feedback. That was helpful because I knew where to be careful. Without this additional training I would have made far more mistakes” . Karen, aged 62 years, who was experienced in physiotherapeutic exercises due to an earlier episode of back pain as well as yoga, described that due to her exercise experience she “knew how her body reacts to exercising”. She additionally reported that she already knew many motions and exercise elements from her years of practicing yoga.Both study patients with and without prior exercise experience consistently performed the app exercises. Moreover, they mentioned problems only occasionally and limited to one or two exercises. The exercise called “Superman” was particularly difficult for several patients. In this exercise the patients had to stand with a forward leaning trunk and raise the arm and contralateral leg at the same time. “I performed all exercises, but there was this one which I had problems with. I mean I did not experience any pain, but it was just very difficult for the muscles. I just could not do it.” . Moreover, some patients experienced performing exercises in a prone position very difficult. Olga, aged 49 years, reported being unable to perform these exercises due to her extreme obesity and Robert, aged 63 years, answered the question why he hated those exercises with, “you are lying prone facing the mat. I do not like that. In the past, I have done some yoga with my wife, but those exercises lying on the belly facing the mat, I will have to say thanks but no thanks. That is because I am having the impression of suffocating.”Independent of age or exercise experience nearly all study patients reported no fear of doing anything wrong while exercising or that they would have felt safer under the supervision of a therapist. “No, actually I was not frightened at all to do anything wrong. The exercises are not that complicated.” . Answering the follow-up question if the presence of a therapist would have increased his perception of safety he answered, “No, I think that is irrelevant. I mean a therapist will surely be in the position to assess more, but I do not think that I had exercises in which that was not possible to do myself.” George, aged 43 years, who described himself as overweight and inexperienced regarding physical exercises answered the same question with, “No, the exercises were not difficult. If I would have felt safer? Probably I would have felt the same.” With a direct reference to the smartphone app Michaela, aged 45 years, said: “Everything was demonstrated well, and the exercises are not those where you would fear that you could hurt yourself”; however, there were two patients, both with no prior exercise experience, who reported that they occasionally felt kind of uncertain with specific exercises and that they would have felt safer under the supervision of a therapist. “When lying on the floor, for example, when they said in the instructional video, ‘extend the head and stretch the spine’, yes you could see it in the video, but if I did it correctly? I don’t know.” . Also, one of the older patients said: “I have only one problem, that is when I am lying on the floor, to get back up again”. . It would have been easier for her, if someone would have helped her up after the exercises on the floor.The question if the patients felt any improvement was answered on two different levels. On the one hand, patients reported the physical improvement: “At first the exercises were rather easy, but then there were some new, strenuous exercises which were particularly exhausting the first few times I had to do them. Over time these exercises became less exhausting and I did not sweat that much or became out of breath that much anymore”  and, “I can move my head further back now” . On the other hand, patients reported an improvement in the management of their exercise protocol: “Because I realized how much time it takes, which object I needed … chair, or whatever equipment I needed to prepare”  and, “It became easier because I then already knew the exercises and knew how they worked, but otherwise not.”  and, “It became easier over the time course of 4 weeks. You know to bring yourself to do it. That you just do the exercises” .The study patients reported that the prescribed exercises were generally not perceived as exhausting; however, there was a high level of heterogeneity regarding the individual perception of the exercises. Some participants reported that the exercises were too easy for them: “I would have thought that the exercises were more exhausting. But with respect to the … ‘aim’ so to say, I think it was actually good because you had to be much more focussed on the exercises themselves. Thus, in my opinion, the primary focus lies on the precision of the exercise execution and to concentrate to the point … the affected muscle, and body region. Actually, when I realized that I nearly had an epiphanic moment.” .Most patients did not realize a visible change in their physical parameters. Some explicitly mentioned that they thought that the exercises were to light for a substantial improvement of their physical performance: “My physical performance did not increase. The exercises were not that exhausting.” ; however, a few patients still reported increased respiration and muscle tone while exercising, and slightly delayed onset muscle soreness was reported infrequently.The fact that relaxation exercises were part of the smartphone app received particularly positive reception in the study patients independent of prior exercise experience or sex: “Yes, I could have imagined exercising at a higher intensity, but I actually really liked that there was also a focus on relaxation techniques. Because they—and I would not have thought it—were of huge advantage for me. I actually thought that only the strenuous exercises would be beneficial for me but that is not the case. That is not true” . Only one patient had a contrary perception regarding the relaxation exercises: “Less relaxation exercises … there were just too many of them” .Generally, messages from the physician with the aim to motivate and encourage the patients were perceived very positively; however, most of the patients would have wanted to have a “re-feedback” system to answer to the messages they received from their physician. “Actually, I would have loved if it would not have been only unidirectional messages but that I could have communicated with the physician. I can imagine that he will not be able to go into every detail when he has got patients in his office, but because I have only those three smileys to rate the exercise, I cannot give detailed feedback which bothers me. Being able to send messages to the doctor could maybe improve this” . The aspect of practicability was also mentioned in this context: “It would be great if you could add something to the smileys. I mean, I do not know if this would even work, if he had time to read everything and so on … That’s also the question. Because if you could write something but the doctor does not have time to read it then it is better if this option is not even there” . Particularly when there is a problem the option to send a more detailed response would have been helpful: “You are getting a message but you cannot react in any way … One exercise, for example, I ranked only mediocre and received the answer: try again! And then I was insecure and thought: ‘If it might be painful for me, I do not want to do it again. How do I solve this situation?’ Certainly, I could have called the doctor but this is not the intention” .Most of the study patients could imagine performing the exercises in various environments and not just only at home. Particularly seated exercises were assessed to being easily carried out at the workplace; however, some limitations were mentioned: “It depends on the exercise. The exercises where I have to lie on the floor certainly not, but maybe those sitting on a chair … You know those exercises where you cannot easily see that you are exercising. I can imagine doing those exercises as a matter of principle”  and similarly, “knowing someone could watch me while exercising is no fun” . That the particular work environment is essential for the execution at the workplace became obvious: “Neither the premises, nor—I am going to be honest with you—the well-being or whatever you want to call it, would fit … I work in a workshop, a large-capacity workshop with forklift traffic, where it is dirty” .p = 0.007). Regarding the questionnaires, the ODI decreased significantly  representing diminished back pain. And in the assessment of quality of life, the SF-36 subscales “physical functioning” , “bodily pain”  and “vitality”  increased significantly with higher values representing higher quality of life. Post hoc power analysis of these significant parameters showed the largest effect size in the SF-36 subscale “bodily pain” (Cohen’s dz = 0.744). When transferring this effect size to an “a priori” sample size calculation with the level of significance (α error probability) set at 0.05 and the power (1—β error probability) at 0.80 the required sample size was calculated at 17 participants  and other parameters were noted of which the clinically relevant ones are depicted here and in detail in Table Back pain is not just a debilitating condition for patients but also a substantial burden for national economies , 14. TheMobile health devices  have been on the rise as tools for the self-management in various diseases and have been currently discussed controversially regarding their feasibility and efficacy , 16, 17.Regarding the correlations, two details caught the eye from a clinical perspective. First, age was associated with back pain at baseline but not at the follow-up anymore. It therefore seems as if the therapeutic exercises were able to diminish the effects of age on back pain. This is in line with the current literature which showed that exercise alone can reduce the risk of back pain . Second,As in any study, this one has limitations as well. Interviews were not undertaken with all participants but only with about half of the included patients; however, as it had been shown that sociodemographic characteristics between the patients undertaking interviews and those who did not were similar at baseline, this is negligible. Moreover, a larger sample size would have been desirable; however, due to the qualitative study design the primary aim of this study regarding feasibility and acceptance could be clarified conclusively, while the post hoc power analysis and sample size calculation clearly showed the distinctive strengths and limitations of the quantitative results.The results of the qualitative analysis showed that it was feasible and well accepted in a typical patient population. Moreover, quantitative secondary data, which was initially collected for power analysis purposes only, already showed significant improvements in back pain and quality of life. This is in line with previous literature , which sSpecialist prescription of a tailored therapeutic exercise program via a smartphone app for patients suffering from non-specific back pain is feasible and well accepted. Pilot data additionally point towards efficacy of the intervention.


Impairment of visual function is one of the major symptoms of people with multiple sclerosis (pwMS). A multitude of disease effects including inflammation and neurodegeneration lead to structural impairment in the visual system. However, the gold standard of disability quantification, the expanded disability status scale (EDSS), relies on visual assessment charts. A more comprehensive assessment of visual function is the full contrast sensitivity function (CSF), but most tools are time consuming and not feasible in clinical routine. The quantitative CSF (qCSF) test is a computerized test to assess the full CSF. We have already shown a better correlation with visual quality of life (QoL) than for classical high and low contrast charts in multiple sclerosis (MS).To study the precision, test duration, and repeatability of the qCSF in pwMS. In order to evaluate the discrimination ability, we compared the data of pwMS to healthy controls.n = 54), we analyzed the benefit of running 50 instead of 25 qCSF trials. The repeatability cohort (n = 44) was assessed by high contrast vision charts and qCSF assessments twice and we computed repeatability metrics. For the discrimination ability we used the data from all pwMS without any previous optic neuritis and compared the area under the log CSF (AULCSF) to an age-matched healthy control data set.We recruited two independent cohorts of MS patients. Within the precision cohort (p < 0.01).We identified 25 trials of the qCSF algorithm as a sufficient amount for a precise estimate of the CSF. The median test duration for one eye was 185 s (range 129–373 s). The AULCSF had better test–retest repeatability  than visual acuity measured by standard high contrast visual acuity charts or CSF acuity measured with the qCSF . Even better repeatability (MAP = 0.19) was demonstrated by a CSF-derived feature that was inspired by low-contrast acuity charts, i.e., the highest spatial frequency at 25% contrast. When compared to healthy controls, the MS patients showed reduced CSF (average AULCSF 1.21 vs. 1.42, High precision, usability, repeatability, and discrimination support the qCSF as a tool to assess contrast vision in pwMS. Visual impairment can be one of the major symptoms in multiple sclerosis (MS) patients. Because vision is rated as one of the three most important bodily functions by MS patients, its impairment has a high impact on quality of life QoL; . StructuCurrently, visual impairment in clinical practice is usually assessed by the Snellen chart, which records high-contrast visual acuity (HCVA) . For exaWe recently showed that qCSF could be a useful tool for the assessment of visual function in MS patients as it correlated best with vision-related QoL measured by the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ) , whereasn = 54 in the precision cohort; and (ii) n = 44 in the repeatability cohort. Within the precision cohort, we aimed to compare the precision of two different test settings for the qCSF device, namely 25 vs. 50 qCSF trials. The repeatability cohort performed two consecutive qCSF assessments at a single visit to determine within-session variability with the previously established number of trials, and an additional HCVA assessment, which was chosen as the most commonly used standard clinical visual outcome measure. We assessed the typical median test duration for the qCSF method in the repeatability cohort. The cohorts were recruited sequentially without any overlap in the recruitment periods; thus, no patient was included in both cohorts. For an evaluation of the ability of the qCSF to discriminate between normal vision and abnormal vision in MS, we pooled the patients with a RRMS disease course and without any current or previous optic neuritis of both cohorts  and compared them to a published normative dataset of 61 age-matched healthy controls (186 measurements because some subjects were tested repeatedly at two visits about a week apart)  . The diaAll tests were performed in the same room, under the same daylight illumination, and in the same order for both MS cohorts; the same stipulations applied for the normal healthy controls tested at a different site. Each eye was assessed separately and measured with best habitual correction . For the precision analysis, the repeatability and the analysis of the time duration we treated within-subject eyes as independent measurements, for the discrimination analysis we averaged the available measurements per subject. To assess the full CSF, for each of the 25 trials, the qCSF device  presented three bandpass-filtered Sloan letters of varying size and contrast on a 46-inch computer screen at a viewing distance of 4.5 m (for details see The shape of the CSF can be modeled with four parameters: (i) peak spatial frequency, (ii) peak contrast sensitivity, (iii) bandwidth, and (iv) a low-frequency truncation parameter . The qCSt-test on the AULCSF summary statistic.Because the ground truth of the actual CSF of an observer is unknown, we estimated the accuracy by calculating the convergence in the precision cohort by running the qCSF for 50 trials. We also calculated the difference of the CSF estimates after 25 and 50 trials (mean bias and mean absolute bias). For calculating the within-visit test-retest repeatability we used the Bland-Altman coefficient of repeatability (COR) . HoweverWe have already shown that 25 trials of the qCSF algorithm are sufficient for a good estimate of the CSF in MS patients . Howeverone-sample t-test t (104) = −4.34, p < 0.001). In line with previous work and the negligible benefit above 25 trials compared to the cost of additional test time, we performed subsequent testing and analyses with 25 trials.Two of the 54 included subjects with MS were measured monocularly only because they had no remaining vision in one of their eyes. One measurement in one subject had to be excluded due to technical problems. This resulted in a total of 105 qCSF measurements. Next, we assessed the individual within-visit reliability of two repeated tests in the repeatability cohort of MS patients. We included 44 subjects with one who was measured in one eye only. This resulted in 87 pairs of test and retest measurements; one eye was excluded from the CS4 calculation because its contrast sensitivity was too low (no stimulus size could be recognized at 25% contrast). Test duration is an important factor for clinical usability. We looked at the duration between subsequent tests of 25 trials each for alternating eyes in the repeatability cohort . As the data were not normally distributed, we fit a mixture of two Gaussian distributions . Median test duration per eye including all preparation, such as changing the eye patch and a break between eyes, was 185 s . On average, MS subjects  had reduced CSF results when compared to healthy controls , Welch’s t (36.28) = 4.77, p < 0.001). The most pronounced difference is seen on the top left side of the curve indicating a larger gap of performance for large and medium-sized letters at low contrast , excluded all patients with a previous optic neuritis or an unknown visual symptom history and compared them to a normative data set of age-matched healthy normal controls , but implementation of such outcomes is still rare . We founThe second aim of our study was to evaluate the repeatability performance of the qCSF method in MS patients. First, we found that the visual function estimate did not differ substantially between two separate assessments in each individual, i.e., we found high stability of the method or high intra-individual reliability. This held true for both the evaluated parameters of the qCSF and for visual acuity VA500. However, care must be taken not to confound the commonly reported COR as a tool to compare tests with different outputs. The smaller range and the strong quantization of VA500 scores led to a seemingly excellent COR. However, repeatability (or precision) is only a necessary but not sufficient condition for the more important quality of a biomarker, which is the sensitivity to detect changes in the underlying signal. In the absence of a ground truth of visual change, we hypothesize that different individuals differ in their visual function, and the MAP metric quantifies the discriminant ability of a test for each individual in comparison to the whole group. Here, in a reversal of the ranking based on the COR, the summary statistic AULCSF provided higher discriminant ability than VA500 and CSF acuity.Similar to low-contrast Sloan VA charts, we further calculated the cut-off frequency for stimuli presented at 25% contrast (CS4), and found that this parameter was even more precise than the AULCSF. In principle, the combination of several parameters, or the distributions thereof, might provide even further precision gains. This also demonstrated the advantage of estimating the full CSF versus paper charts that are limited to a fixed contrast level (HCVA or LCVA) or fixed spatial frequency  . In addiFurthermore, we also assessed typical test duration. With an average of about 3 min, results are in agreement with previous qCSF data from healthy controls . Taken tThe descriptive analysis comparing average CSF estimates from MS and healthy controls indicates a worse performance over the complete frequency range with marked impairment of sensitivity to lower contrast levels. This finding in our study is consistent with reports for Sloan charts, that provide best discriminant abilities for MS with 1.25 and 2.5% low contrast VA charts. While 0.6% seems to be biased by a floor effect, 5% charts are already limited by a raising ceiling effect . The qCSThe main limitation of the current study was the lack of comparison with Sloan VA charts in MS patients. However, we aimed to keep the burden for recruited patients low and decided to contrast our findings only with the clinical and EDSS standard, which is HCVA with a Snellen chart. Interestingly, repeatability data for Sloan charts in MS patients have not been previously published, although a good intra-rater agreement has been reported (ICC 0.86–0.95) . It shouTaken together, qCSF provides excellent test characteristics and has already been linked to visual quality of life in MS. Our findings indicate that the further evaluation of the qCSF method in longitudinal studies as an outcome measure for MS seems promising. These studies should also include comparisons to the Sloan VA charts.The raw data of all MS patients supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of the Board of Physicians in the State of Hamburg and the Institutional Review Board at the Nova Southeastern University in Fort Lauderdale, Florida. The patients/participants provided their written informed consent to participate in this study.J-PS conducted and designed the experiments. AKB designed the study involving healthy controls. SCR, MD, and J-PS analyzed the data and wrote the manuscript. BK analyzed the data. HZ and AKB supervised the study and wrote the manuscript. All authors contributed to the article and approved the submitted version.MD holds equity in and employment by Adaptive Sensory Technology and holds patents related to the qCSF. The qCSF device was provided to INIMS free of charge; no further compensation was granted. HZ received research grants from Novartis and speaking honoraria from Bayer Healthcare, unrelated to this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Low back pain is a common condition among older adults that significantly influences physical function and participation. Compared to their younger counterparts, there is limited information available about the clinical course of low back pain in older people, in particularly those presenting for chiropractic care. Improving our understanding of this patient population and the course of their low back pain may provide input for studies researching safer and more effective care than is currently provided.The primary objectives are to examine the clinical course over one year of pain intensity, healthcare costs and pain, functional status and recovery rates of low back pain in people 55 years and older who visit a chiropractor for a new episode of low back pain.An international prospective, multi-center cohort study with one-year follow-up. Chiropractic practices are to be recruited in the Netherlands, Sweden, United Kingdom and Australia. Treatment will be left to the discretion of the chiropractor. Inclusion/Exclusion criteria: Patients aged 55 and older who consult a chiropractor for a new episode of low back pain, meaning low back pain for the first time or those patients who have not been to a chiropractor in the previous six months. This is independent of whether they have seen another type of health care provider for the current episode. Patients who are unable to complete the web-based questionnaires because of language restrictions or those with computer literacy restrictions will be excluded as well as those with cognitive disorders. In addition, those with a suspected tumor, fracture, infection or any other potential red flag or condition considered to be a contraindication for chiropractic care will be excluded. Data will be collected using online questionnaires at baseline, and at 2 and 6 weeks and at 3, 6, 9 and 12 months.This study, to our knowledge, is the first large-scale, prospective, multicenter, international cohort study to be conducted in a chiropractic setting to focus on older adults with low back pain consulting a chiropractor. By understanding the clinical course, satisfaction and safety of chiropractic treatment of this common debilitating condition in the aged population, this study will provide input for informing future clinical trials.NL7507.Nederlandse Trial Registrar  Worldwide, low back pain is the leading cause of years lived with disability and contributes to the global burden of disease , 2. Low Low back pain is generally more severe with increasing age . For exaChiropractors provide a significant portion of care for patients with low back pain , and carIn short, there is a general lack of knowledge regarding low back pain in older adults, but more importantly, data are lacking on course of low back pain for this population in a chiropractic setting , 16.The current BACE-C consortium study has been modelled after the ‘BAck Complaints in Elders’ study (BACE), which is an international cohort study devoted to examining back complaints in older people in primary care . The BACStudy design. This study is designed as an international, multi-center prospective cohort study. Data are to be collected from patients 55 and older with low back pain who visit a chiropractor. Follow-up measurements will be scheduled at 2 weeks, 6 weeks, 3 months, 6 months, 9 months and at one year after the first treatment. Participants are to be recruited from the private practices of chiropractors in the Netherlands, Sweden, Australia and the United Kingdom using the same recruitment strategies. The procedures and design outlined in this paper are to be followed by the participating countries and describe a common set of primary outcome measures and patient- and chiropractic factors to be measured. Care will be at the discretion of the participating chiropractors. Ethics approval will be obtained in each participating country prior to data collection.Patients aged 55 and older who consult a chiropractor for a new episode of low back pain, meaning low back pain for the first time or those patients who have not been to a chiropractor in the previous six months. This is independent of whether they have seen another type of health care provider for the current episode. All low back complaints, with pain in the region from the thoracolumbar 12th rib junction to the first sacral vertebrae, including pelvic pain and pain referral to the leg(s) are to be included. Chiropractors who are licensed and currently work in clinical practice will be asked to participate.Patients who are unable to complete the web-based questionnaires because of language restrictions or computer literacy restrictions will be excluded as well as those with cognitive disorders. In addition, those with a suspected tumor, fracture, infection or any other potential red flag or condition considered to be a contraindication for chiropractic care will be excluded.Participating chiropractors will be asked to refer all potential participants who fulfill the inclusion criteria to the online questionnaire, preferably prior to the first appointment. Participants will be briefly informed about the study procedures over the phone when they call to make an appointment or during the initial consultation with the chiropractor. The chiropractor or chiropractic assistant will ask for the patient’s permission to send an email with a link to the informed consent and baseline questionnaire, so that it can be completed at home prior to the first visit or as soon as possible and no later than two weeks after the initial visit. Figure Links to the questionnaires will be sent by email and completed as a web-based questionnaire at baseline, 2 and 6 weeks, and at 3, 6, 9 and 12 months after the initial visit. In Sweden data will not be collected after 6 weeks because of logistical burden. Table The primary outcome measures are: 1) low back pain intensity, 2) back-specific functional status and 3) global perceived effect. As a secondary measure, 4) healthcare costs will be measured. All outcomes are self-reported.Patient-related factors: The following factors will be measured at baseline: 1) sociodemographic characteristics ; 2) physical activity ; 3) othIn the Netherlands, each chiropractor will also perform at the first consult the “timed Up & Go” test . The “tiPain intensity will first be measured using an 11-point numerical rating scale (NRS)  in whichFunctional status will be measured at baseline and all follow-up intervals using the Roland Morris Disability Questionnaire (RMDQ) , in whicGlobal perceived effect (GPE) will be measured on a 7-point scale, ranging from ‘completely recovered’ to ‘worse than ever’ , 29. PatHealthcare consumption will include the use of all primary health care , all secondary healthcare , hospitalization, complementary care  as well as the use of both prescribed and over the counter medication. Questions were adapted based on the iMTA medical consumption questionnaire . HealthcThese variables will be obtained from the chiropractors themselves: 1) sociodemographic , school attended , and types of treatments commonly delivered in their practice. Data collection is based upon consecutive inclusion of patients, but recognize that this may represent ‘convenience sampling’. Ideally, the patient is to complete the baseline questionnaire prior to the first appointment; however, it may be completed following the first visit. At the end of the data collection period, chiropractors will also be asked to submit treatment dates of patient during the year of inclusion, which will give an indication of dosage and frequency. These characteristics will be included where deemed relevant in the analysis.In the Netherlands and in Sweden, each chiropractor will be asked to fill in several questions about their expectations of patient recovery. This will be asked at the first four treatment visits.Baseline variables will be presented as percentages for categorical variables and as means plus standard deviations for continuous variables. In case of non-normal distributions, continuous variables will be described as medians with corresponding interquartile ranges. Furthermore, descriptive information of the primary and secondary outcome variables will be presented for baseline and all follow-up intervals. Descriptive analyses will be conducted for the entire data set from all participating countries as well as stratified for each country.The primary objective will be answered using the entire data set from all participating countries and subsequently stratified by country.In addition, the primary objective will be answered for each primary outcome separately by multilevel models with three levels . Country will be included as a covariate in the models (as dummy variables) . The modp-values.The clinical course of pain and back-specific functional status will be analyzed by linear multilevel models, global perceived effect by logistic multilevel models and healthcare costs by a linear multilevel model with bootstrapped confidence intervals because of the expected skewed distribution of the cost data. We will report regression coefficients (linear models), odds ratios (logistic models), corresponding 95% confidence intervals and two-sided Given that the baseline data collection allows for flexibility of inclusion (i.e. patients may complete prior to or following their first visit), this broad window for data collection has the potential to significantly impact baseline values, and subsequently each of the three primary outcome measures. Therefore, in order to deal with this problem, we will correct for this in the analyses, specifically the pain trajectories and reporting outcome. Patients are to be included consecutively, but we recognize that inclusion represents a ‘convenience sample’.We know when patients completed the baseline questionnaire and will examine in a sensitivity analysis whether there are differences in the outcomes between those who complete the questionnaire prior to the first visit as opposed to completing if after their first visit. A paper version was designed for those who prefer not to participate, yet willing to complete a questionnaire one-time only prior to the first visit. We will compare both patient groups on demographic information as well as the primary outcomes in order to determine whether there is selection bias in our sampling. We recognize that those who receive ‘care-only’ or ‘care-only plus maintenance/supportive care’ may have different trajectories and outcomes; therefore, we will stratify these analyses for these groups should there appear to be fundamental differences. In order to classify this variable, two of the investigators  will examine the frequency and dosage of care for the entire year, independently of one another. We do not have a specific hypothesis that we are testing; therefore, we did not perform a power calculation. As this is an international study, we expect to be able to recruit approximately 600 patients in order to answer the primary objectives.This study is to our knowledge the first large-scale, prospective, multicenter, international study to be conducted in a chiropractic setting and the first one focusing on older adults with low back pain consulting a chiropractor. The primary objectives of the BACE-C study are to examine the clinical course over one year of the intensity, healthcare costs and improvement rates of low back pain in patients aged 55 and older who consult a chiropractor for a new episode of low back pain, meaning low back pain for the first time or those patients who have not been to a chiropractor in the previous six months. This is independent of whether they have seen another type of health care provider for the current episode. By understanding the impacts of various factors on the course and treatment of low back pain in the elderly population, this large data set will allow us to provide input for the development of future feasibility intervention studies in this patient group.We will not be linking our database with claims data as these are not readily available, and we do not have the resources to do this, but will rely on self-reported data from participating patients. We recognize that this is a potential limitation, because of possible information bias. However, we aim to estimate total healthcare consumption, including OTC and non-declared care as well (which is not necessarily available from claims data). As well baseline data will be collected at various time points either before or after patients has been treated. This could also be a possible limitation and the software will timestamp the questionnaires and we will also receive treatment dates from the chiropractors, so we can minimize this limitation and evaluate the baseline date as covariates in the analysis.An additional limitation to the study is the timing of completion of the baseline questionnaire, where patients will be able to complete the questionnaire prior to or following the first visit. This flexibility was introduced in order to make patient inclusion for the chiropractors easier; however, it does introduce a potential limitation, namely, such a broad window for baseline data collection has the potential to impact the primary outcome measures. Our plan is to correct for potential differences in the analysis. The most important implication of this study is that it will provide data where these are currently lacking. Specifically, this study will give insight into the use and course of chiropractic care in the elderly with low back pain. This is consistent with the call to action from the recent Lancet series on low back pain. The results from this study may influence clinical practice if it means that the course, costs and improvement for this population are different than their younger counterparts with low-back pain. We invite other research groups worldwide to join the BACE-C consortium.Data will be stored on institutional network drives with firewalls and security measures in place according to national and European Union data protection regulations. Hard copy records will be stored in a locked cabinet in a secure location. Access to records and data will be limited to study personnel. Study data will be de-identified and a master log file with identifiers will be kept and stored separately from the data. Only anonymized data will be used for analyses.


Propionibacterium acnes lysate gel (Emorsan®Gel) on pain control after OEH. Research design and methods: Fifty consecutive patients undergoing OEH were included. All patients received stool softeners and oral analgesia in the post-operative period. Emorsan®Gel was also used topically by the last 25 patients (Emorsan®Gel group (EG)) until Post-Operative Day 20 (POD 20). The primary outcome was the effectiveness of Emorsan®Gel on pain relief using an 11-point visual analogue scale (VAS). Morbidity, wound healing (WH), and time to work were documented at POD 1, POD 10, POD 20, and POD 40. Results: Of the 50 patients enrolled, twenty-eight (56%) were males; median age, 49  years. The VAS score decreased over time in all patients, with significantly lower scores at POD 20 in the EG  vs. 2.12 (0.93) in the control group (CG); p = 0.045). All patients in the EG achieved complete WH at last follow-up, compared to only 17 (68%) in the CG (p = 0.004). The likelihood of WH was 66% higher in the EG . Conclusions: Emorsan®Gel is safe and effective at reducing pain after EOH, promoting earlier WH compared to standard care treatment.Background: Pain is the most common complication after open excisional hemorrhoidectomy (OEH). We assessed the effectiveness of polycarbophil and  Open excisional hemorrhoidectomy is the gold standard treatment of III and IV degree hemorrhoidal disease (HD) . HoweverPost-operative pain represents a major burden for patients. It is frequently experienced during the first 7–10 days after surgery  and may ®Gel  is a topical gel rich in dimethicone and cyclopentasiloxane. These substances protect the skin and mucous membranes from external agents [Emorsanl agents ,9. Theirl agents . Furtherl agents .®Gel in the post-operative management after open diathermy excisional hemorrhoidectomy.The aim of the present study is to assess the short-term outcomes of EmorsanBetween January and December 2018, fifty consecutive patients were prospectively included in the “EMORGEL Study”, approved by regional ethics committee “Sezione Area Centro, Regione Calabria”; Approval Code 84/19). Written informed consent was obtained from all patients.Consecutive subjects aged between 18 and 75 years, undergoing open diathermy excisional hemorrhoidectomy for Goligher III or IV degree HD were included in this study. The procedures were performed according to the PROSPECT (PROcedure-SPECific post-operative pain management) evidence , and neiPre-specified exclusion criteria were: pregnancy, current use of specific medications , active cancer, previous open hemorrhoidectomy, known allergy to product components.®Gel group (EG)) enrolled at intervals of 6 months . All patients received standard care treatment in the immediate post-operative period, consisting of stool softeners and oral analgesia . Only the last 25 patients enrolled  also received Emorsan®Gel topically every 12 h (2 mL per dose) for 20 consecutive days.A block enrolment strategy was used with two cohorts of 25 patients (control group (CG) and EmorsanAll patients were followed up at 4 time points: T1, Post-Operative Day 1 (POD 1); T2, POD 10; T3, POD 20; T4, POD 40. The following data were recorded on each visit: pain severity (spontaneous and/or on defecation) using an 11-point visual analogue scale (VAS); presence of thrombosis (defined as one or more swollen painful piles at the site of the mucocutaneous bridge); hemorrhage; wound status ; use of analgesia; grade of satisfaction on a 5-point scale . Data on bowel habit were also recorded at T2, T3, and T4 using three patterns of the Bristol stool scale  . During ®Gel were recorded at T2, T3, and T4 from the last 25 patients enrolled, using a 6-point score: 0, no erythema; 1, very mild erythema; 2, moderate erythema without edema; 3, moderate erythema with edema without papules; 4, severe erythema with edema +/− papules; 5, severe erythema with edema and vesicles.Any adverse events related to the use of Emorsan®Gel on pain relief. Secondary outcomes were post-operative morbidity, wound healing, and time to work and social life.Primary outcome was the effectiveness of EmorsanAll data were recorded anonymously on a prospectively built electronic database.The study is reported in accordance to the STROBE  guidelines .p-values were reported at their nominal value. Uni- and multi-variable logistic regressions were performed with a pre-defined covariate set, which included age and gender. All statistical analyses were performed using Stata 16 .Continuous variables are presented as the mean and standard deviation, while binary variables as proportions. Comparisons across groups were made using ANOVA and Fisher’s exact tests, respectively. p = 0.776) and age  were similarly distributed in the two groups  were males. Median age was 49 (interquartile range (IQR), 43.5–56) years. Gender  and urinary retention .Mean operative time was 24.3  minutes in the EG and 25.3  minutes in the CG. Morbidity occurred in six (12%) patients: bleeding . Although not reaching statistical difference, the VAS mean score over time was 0.1 points lower in the EG vs. CG (The VAS score decreased likewise over time . HoweverG vs. CG .Thrombosis was observed at T2 and T3 in two (8%) patients in the CG and spontaneously resolved at T4. None of the patients in the EG experienced this complication, nor adverse events. No cases of hemorrhage were noted.p = 0.004). The likelihood of wound healing was 66% higher in the EG, although not reaching statistical significance (odds ratio (OR), 1.66 )  in the CG ( 0.172)) .p = 0.846).Bowel habit similarly improved in both groups from T2 to T4: the number of patients achieving normal stool consistency passed from 19 (76%) to 20 (80%) in the EG and from 18 (72%) to 22 (88%) in the CG ; mean CG, 4.60 (0.58)).Several medical and surgical strategies have been developed to improve the post-operative management of patients undergoing open excisional hemorrhoidectomy ,22,23,24Post-operative pain is one of the oldest and most debated problems after hemorrhoidectomy. Although the VAS mean score was not statistically significantly lower over time in the EG vs. the CG, at POD 20 (T3), twenty patients in the former group achieved a higher benefit compared to the controls. A similar outcome was observed in a previous prospective multicenter study on the efficacy of mesoglycan in pain control after excisional hemorrhoidectomy . The higWhile burdened with higher recurrence rates, a better control of pain and faster recovery were observed after transanal hemorrhoidal dearterialization (THD) compared to open and closed excisional hemorrhoidectomies . The abs®Gel benefited all patients receiving the product in terms of wound healing at 40 days after surgery. While higher in the EG, the likelihood of wound healing did not reach statistical significance, possibly due to the small sample size. However, earlier wound healing observed in the EG may explain the better pain control at 20 days after surgery.Our results demonstrated that the use of Emorsan®Gel forms a tight epidermal barrier and may reduce local oxidative stress through the action of polycarbophil and Propionibacterium acnes extract. Indeed, the radical scavenging property of Propionibacterium lysate prevents cell damage from oxygen free radicals, thus reducing the inflammatory process.In a previous work, we highlighted the role of inflammation in the pathogenesis of HD by demonstrating a high level of matrix metalloproteinases in patients with III and IV degree hemorrhoids . In thisSuch anti-inflammatory properties could contribute to limit post-operative edema that may eventually cause thrombosis. This often involves the muco-cutaneous bridges and represents the most frequent cause of pain. Of note, none of the patients in the EG experienced this complication, as opposed to 8% of subjects in the CG.This study has some limitations including the non-randomization design and the small sample size. However, patients were recruited consecutively to mitigate the selection bias. We also acknowledge the lack of a standardized thrombosis-measuring tool.®Gel on pain control after open hemorrhoidectomy, promoting earlier wound healing compared to standard care treatment. Larger trials are needed to confirm such findings.The results of this study support the safety and effectiveness of Emorsan


Previous studies showed that deep brain stimulation (DBS) relieves pain symptoms in Parkinson disease (PD) patients when programmed for motor-symptom relief. One factor involved in pain processing is sensory perception of stimuli. With the advent of directional leads, we explore whether directional DBS affects quantitative sensory testing (QST) metrics acutely.PD patients with subthalamic (STN) DBS and directional leads were tested in 5 settings  for each of three directional segments of contact used for clinical programming. The Unified Parkinson’s Disease Rating Scale (UPDRS-III) assessed patient’s motor skills at time of study visit at clinical contact and at contact which produced optimal sensory threshold . Correlation analyses were performed between stimulation parameters  and outcome metrics.p = 0.69), warm pain (p = 0.99), Von frey fibers (p = 0.09), pin-prick (p = 0.88), vibration (p = 0.40), pressure (p = 0.98)]. With correlation analysis, increasing PW at the posterior contact increased pin prick and vibration sensitivity (p < 0.001). Additionally, an increase in TEED caused a decrease in sensitivity to warm detection when using the anterior (p = 0.04), lateral (p = 0.02), and medial contacts (p = 0.03), and also caused a decrease in sensitivity to cold detection when using the medial contact (p = 0.03). UPDRS-III remained stable during testing.Sensory thresholds were obtained in nine patients. Directional stimulation did not significantly alter patient perceptions of sensory stimulus [cold pain (Motor benefit can be acutely maintained at directional contacts, whereas directional stimulation can modulate thermal and mechanical sensitivity. Further investigation will determine whether these changes are maintained chronically or can be improved with optimized programming. The progressive nature of the condition can result in severe motor impairments that could lead to a patient’s loss of independence. The prevalence and severity accounts for a $52 billion USD burden on our healthcare system Parkinsons Foundation (2019)1. Early in diagnosis, levodopa is often prescribed in conjunction with carbidopa (termed L-DOPA) to replenish depleted dopamine supplies in the striatum (Parkinson’s disease (PD) is a debilitating neurodegenerative disorder that affects over 10 million people worldwide Parkinsons Foundation (2019)striatum . When pastriatum . In addistriatum . In PD pstriatum . The stuThe use of directional leads, which alter current distribution to more precisely target the STN, is a novel addition to DBS which has resulted in larger therapeutic windows and higher side-effect thresholds while maintaining improvements in motor function . HoweverIn this study, participants were considered eligible if they had previously been diagnosed with PD and had undergone standard of care implantation of bilateral or left-sided directional STN DBS lead(s). Those who qualified for surgical treatment had completed the Unified Parkinson’s Disease Rating Scale motor scale (UPDRS-III) and neuropsychological testing as part of the standard unit of care. Patients must have had improvement of more than 30% on the Core Assessment Program for Surgical Interventional Therapies (CAPSIT) to be an eligible candidate for surgery. Patients who demonstrated dementia, significant cognitive impairment, or unstable psychiatric disease were considered ineligible. Subjects enrolled in this approved study were fluent in English and competent to consent to participation.Patients completed questionnaires at the start of the visit to gauge the pain level of the patient, assess sensitivity to daily activities, and assess their perception of specific pain types at their clinical settings. The questionnaires included the Numerical Rating Scale (NRS) and the King’s Parkinson’s Disease Pain scale (KPDPS). Using NRS, patients were asked to rate (1) pain at its worst during the previous week, (2) pain at its best during the previous week, (3) pain on average, and (4) current pain. Using KPDPS, patients were asked to rate their severity (0-3) and frequency (0-4) of their pain in (1) musculoskeletal pain, (2) chronic pain, (3) fluctuation-related pain, (4) nocturnal pain, (5) oro-facial pain, (6) discoloration, and (7) radicular pain all in the last month as it related to PD. Additionally, the location and history of a patient’s primary source of pain was recorded prior to sensory testing.The participant then went through a series of QSTs for about 1–1 1/2 h at different settings to assess detection and pain thresholds for mechanical and sensory stimuli. Only the left lead was tested based on anecdotal evidence in our patient population that left sided implants had greater pain responses. Testing one lead also controlled for heterogeneity and the confounding factor of bilateral stimulation. Additionally, this testing reduced patient fatigue and increased recruitment and ability to give a response as the testing session was usually coupled to a previous appointment and lasted over an hour. If a patient had bilateral DBS, the right STN lead was turned off for the duration of the study visit and returned to the clinical settings following conclusion of the study.Tests were run at five stimulation settings: first with DBS off, once with each DBS directional contact  turned on individually, and once with the full directional contact on. If the patient’s optimal clinical contact was not directional, then the contact used during testing was the directional contact in closest proximity to the clinical contact. In the case that the patient’s optimal clinical contact had directionality functioning, then the same contact was used during testing. These stimulation parameters were adjusted on the directional lead closest to the patient’s optimal clinical contact with the programming neurologist. A minimum of 2 min was allotted between programming changes.All sensory testing was completed on the patient’s lower right back, approximately 3 centimeters superior and medial to the posterior iliac crest. Testing was performed on the lower back due to the relatively high incidence of lower back pain in the PD patient population , and hasUpon completion of sensory testing, the settings which elicited the best sensory response for each patient was determined. This was determined by first evaluating which stimulation parameters elicited the least amount of pain associated with the 40 g weighted pinprick. Then pressure thresholds, sensitivity to VFF, cold/hot pain and cold/hot detection were taken into consideration in successive order. Once the best QST settings were identified, the patient was put under these settings once again, and assessment of the patient’s motor skills was performed using the UPDRS-III motor examination. Once this was complete, the patient’s device was returned to the clinical settings agreed upon by the patient and their treating neurologist. This UPDRS-III score was compared to each patient’s pre-operative UPDRS-III scores as well as their UPDRS-III scores at their optimal clinical setting, which had been previously collected by the patient’s neurologist.p-value less than 0.05 was considered statistically significant.For demographic and sensory data, repeated measures ANOVAs were performed. Individual statistics were assessed across the five different stimulation settings for each patient and performed for each sensory test. Additional analysis was performed for each sensory test based on the patient’s current clinical settings  and the patient’s report of pre-operative pain (pain or no pain). Additionally, a correlation analysis was conducted between stimulation parameters  and outcomes at every contact tested . A In total, nine patients with STN-DBS for PD were enrolled in this study; they had been diagnosed with PD for 13.3 ±1.98 years (mean ±SEM) and were 66.4 ±1.69 years of age (mean ±SEM). Patients underwent sensory testing 12.8 ±1.8 months post-operatively (range 2–19 months). Eight patients were implanted with bilateral STN leads, and one patient was implanted with a unilateral left STN lead. Three patients experienced chronic pain (pain > 3 months) preoperatively, and six patients did not see . Patientp > 0.1)  see . A multip = 0.69, warm pain p = 0.99, Von frey fibers (VFF) p = 0.09, pin prick p = 0.88, vibration p = 0.40 or pressure p = 0.98]. One patient was removed from the VFF group analysis as the OFF value was greater than 2 standard deviations away from the mean and thus proved to be an outlier. When using VFF, there was a 37.9% increase in sensory threshold using directional stimulation compared to DBS OFF [1.47 ± 0.76 (mean ± SEM)] grams of pressure, although this finding did not reach significance. Individually, two out of nine patients showed this change with medial, 2/9 with lateral, and 3/9 anterior. Two patients showed no change. Further analysis of sensory perception between patients with and without chronic pain showed no significant differences between the two groups in any of the sensory tests we conducted: warm and cold window, warm and cold sense, hot and cold pain, Von Frey Fibers (VFF), 10 and 40 g stimulation direction, vibration stimulation, and pressure stimulation (p > 0.05).This analysis showed that directional stimulation did not significantly alter patient perceptions of sensory stimulus [cold pain p < 0.001; r > 0.99) and vibration sensitivity increased  when using the posterior contacts. When TEED was increased, sensitivity to warm detection decreased when using the anterior , lateral  and medial contact . Additionally, increasing TEED caused a decrease in cold detection sensitivity using the medial contact .Results of the correlation analysis between the stimulation parameters and outcome measures showed that as PW and TEED increased, sensory sensitivity increased when using the anterior, posterior and lateral contact . Specifin = 9), ON clinical DBS settings (n = 8), and DBS ON that evoked greatest sensory tolerance (n = 4). These comparisons showed no statistical differences between DBS ON in the clinical and the best sensory tolerance settings. However, both stimulation of the optimal clinical contact (p = 0.0001) and optimal sensory contact (p = 0.0058) showed improvement in motor symptoms compared to pre-operatively OFF medication  when PW was increased in the posterior contact, but not at other contacts. Furthermore, increasing TEED at the anterior, lateral and medial contacts decreased warm detection sensitivity, and decreased cold detection sensitivity at medial contacts. In other words, decreased thermal detection means that patients felt heat at higher temperatures and cold at lower temperatures. As per mechanical sensitivity, this thermal modulation was likewise reproducible and limited to certain directional contacts. The current literature has mixed results regarding STN stimulation on sensory and thermal thresholds, and is limited to studies using omnidirectional leads. For example, studies have demonstrated both an increased thermal detection threshold with STN-DBS , or no cDeep brain stimulation surgery is an ever-evolving treatment which has shown continuous improvement in treating PD with the development of directional leads within the last decade. These multi-contact leads have shown promise in treating not only the primary motor symptoms of PD but also the prevalent non-motor components of the disease. This study is the first to investigate the effect of directional stimulation on sensory perception in patients diagnosed with PD and receiving STN stimulation. Our findings suggest that directional stimulation can modulate certain modalities of sensory perception in addition to motor symptom relief.We are aware that there are several limitations of this study. This includes the subjective nature of QST, in which pain scales may not be held constant across patients. Additionally, patients were aware of the stimulation parameters being tested during the study. The number of patients studied was small, but is consistent with other dDBS studies at this time. Both lead location and programming parameters, while variable between patients, did not demonstrate any outliers that were consistent with individual variation in DBS among PD patients. UPDRS-III scores at the patient’s optimal clinical contact and without stimulation (medication on and off) were collected during the previous programming sessions and pre-operatively respectively, such that all UPDRS scores for a given patient were not collected on the same day. It is the goal of the authors that future studies include comparisons between the relief of both pain and motor symptoms in a larger population of PD patients whose clinical settings are set to either omnidirectional or directional stimulation. Further investigation with a larger patient population will allow for further comparative sensory testing in patients with and without chronic pain that can identify between-group differences. Additionally, analyzing changes in quality of life measures before and after surgery could elucidate the effect of directional leads on quality of life for PD pain patients. Studying different frequencies may also elucidate the role of directionality versus frequency in sensory changes as it has been hypothesized that frequency may play a larger role in this. However, it has been shown that patients with tremor predominant PD cannot tolerate lower frequencies for motor symptom control which led us to investigate directionality as an alternative approach in this current study .This study aimed to determine the effect of directional stimulation of STN on sensory perception in patients with PD. Directional stimulation resulted in increased thresholds to mechanical stimulation, specifically increasing PW increased pin prick and vibration sensitivity when using the posterior contact. Furthermore, decreased thermal detection sensitivity was seen with increased TEED in specific directional contacts. These findings expand the current therapeutic knowledge of directional DBS beyond the relief of motor symptoms and provide promise for the use of directional leads to modulate certain aspects of sensory perception.The datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by the Institutional Review Board at Albany Medical College. The patients/participants provided their written informed consent to participate in this study.SS helped to organize the project, obtain and analyze the data, write and review the manuscript. OK helped to analyze the data, write and review the manuscript. MD helped to organize the project, obtain and analyze the data, write and review the manuscript. MS aided in writing, reviewing, and critiquing the manuscript. LW helped to obtain and analyze the data and wrote the manuscript. MG obtained the data and reviewed and critiqued the manuscript. JD, EH, and OA provided intellectual aid, reviewed, and critiqued the manuscript. JP developed the study, organized the project, wrote, reviewed, and critiqued the manuscript.JP is a consultant for Boston Scientific, Nevro, TerSera, and Abbott and receives grant support from Medtronic, Boston Scientific, Abbott, Nevro, TerSera, GE Global Research, SBIR 1R43NS107076-01A1, NIH 2R01CA166379-06, and NIH U44NS115111. She is medical advisor for Aim Medical Robotics and Karuna and has stock equity. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.