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Keywords | Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB). | PMC10007824 |
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Introduction | infected instrumentation debris, periodontitis, necrotic | APICAL PERIODONTITIS, PERIODONTITIS, NECROTIC | The ultimate goal of root canal therapy is to prevent apical periodontitis or to allow healing of an existing-apical periodontitis by rendering the root canal system as free as possible from microorganisms. This is accomplished by disinfecting the whole root canal system through meticulous shaping and irrigation [Most often clinicians deal with narrow curved roots in which there is more than one canal, those canals are usually connected through fins or anastomoses. An anastomosis -also called an isthmus- is a narrow space between two root canals that can harbor microorganisms and dentin debris packed into it during instrumentation [Sodium hypochlorite (NaOCl) is the most used irrigating solution. It has a strong antimicrobial effect with the ability to dissolve organic tissue [Anastomosis is a restricted area that harbors remnants of pulp tissue, bacterial biofilm and infected instrumentation debris especially in infected necrotic root canals thus it must be cleaned and disinfected to achieve a favorable outcome, it is well-agreed that the anastomosis cannot be touched by the instruments and is a very difficult area to be reached by the irrigant [The null hypothesis of this study is that there is no significant difference in anastomosis cleanliness at different anastomosis levels between passive ultrasonic irrigation (PUI) using Irrisafe (Satelec, Acteon, France), sonic activation using EDDY, and the control group needle irrigation without activation (NA). | PMC10007824 |
Methodology | PMC10007824 |
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Study design | 3.1.9.2, calculus | All procedures performed were carried out in accordance with relevant guidelines, regulations and ethical standards of the ethical committee of research of the Faculty of Dentistry, Suez Canal University (approval number for the study: 137/2018.)This study was a single-blinded study, conducted on 60 human mandibular first molar teeth extracted for periodontal reason, extracted teeth were collected from the outpatient clinics after approval of the patient. The sample size was calculated according to G*Power software version 3.1.9.2 at a significance level of Teeth were rinsed under running water, then an ultrasonic scaler was used to remove calculus and soft tissue remnants from the root surface, then immersed in 5.25% NaOCl (Clorox, Egyptian Company for household cleaners, Cairo, Egypt) for 10 min for disinfection then stored in distilled water at room temperature till the time of the study. The experimental setup followed the technique described by Klyn et al. which used a copper cube based on the Bramante model [All roots were cut by a diamond disc (Isomet 4000 linear precision saw, Buehler, Lake Bluff, IL, USA) to establish a unified length of 12 mm for all roots for the purpose of standardization, to eliminate the variable of root canal length on the cleaning efficiency between groups.Roots were scanned using cone beam computed tomography (CBCT) unit Scanora 3Dx (Kavo Dental, Germany) with exposure parameters; 90 kVp and 4 mA to detect the presence of a type V isthmus (complete anastomoses between both canals) at 2,4 and 6 mm from the apex and those with a partial connection or without an anastomosis or were replaced. Also, CBCT was also employed to exclude teeth internal or external root resorptions, calcified root canals, open root apices and to measure the angles of roots curvature using the Schneider technique [ | PMC10007824 |
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Samples preparation | CM, WL | A #10 K-file (Dentsply-Maillefer, Ballaigues, Switzerland) was inserted into the root canals until it was visible under the DOM at the apical foramen to ensure the canal is patent. Length was taken, and 1 mm was subtracted to determine the established working length (WL). A glide path was established. The coronal openings were sealed with a cotton pellet and glass ionomer and the apical foramina were sealed by a double layer of nail polish to prevent their blockage by epoxy resin. The roots were sectioned at 2, 4, 6 mm from the apex—due to the higher prevalence of anastomoses in these levels- using an 0.3-mm-thick Isomet low-speed saw with a diamond blade. The blade was irrigated with IsocutPlus Fluid (Buehler, Lake Bluff, IL, USA) and water according to the manufacturer’s recommendations. The sections obtained were put into an ultrasonic bath with distilled water for 7 min to remove the debris originating from the cut. Pre-instrumentation images of the specimens (IHyflex CM rotary files (Coltène/Whaledent AG, Switzerland) were used to instrument all the root canals up to 35/0.04 taper. A total volume of 5 mL 5.25% NaOCl was used in each canal via a 30-gauge side-vented needle as 1 mL after each file. After complete instrumentation, the sections were disassembled, and images were taken (I | PMC10007824 |
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Samples grouping | Sections were reassembled and divided into 3 groups according to the activation method. Samples were blindly and equally distributed among the groups. | PMC10007824 |
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Group 1 (NA) | agitation, WL | 1 mL 5.25% NaOCl was introduced into each root canal and left inserted 1 mm short of the WL in each canal and left without agitation for 30 s. | PMC10007824 |
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Group 2 (Irrisafe) | 1 mL 5.25% NaOCl was introduced into each root canal and an Irrisafe tip (of a size 20/0.00 taper and length of 21 mm (IRR20)) was inserted to 1 mm from the working length, and activated for 30 s at a medium power setting using NSK Varios 370. | PMC10007824 |
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Group 3 (EDDY) | 1 mL 5.25% NaOCl was introduced into each root canal for 30 s and an EDDY tip of a size (25/0.04 taper) attached to the airscaler (AS2000, NSK, Nakanishi, Tochigi-ken, Japan) was inserted to 1 mm from the working length to activate the irrigant for 30 s with 2 mm up & down amplitude in each root canal.In all groups, irrigation was done using a 30-gauge side-vented needle (Steri irrigation tips 30 G, DiaDent Group International, Canada). All samples received a final rinse of 2 mL saline (1 mL in each root canal). Then canals were dried with paper points (Coltène/Whaledent AG, Switzerland). After final irrigation, post-activation images (ITo assess the improvement in anastomosis cleanliness after activation, the difference in percentage of cleanliness before and after activation was calculated by the following equation [While Total isthmus cleanliness of each root was calculated as an average of the three levels (2, 4 and 6). | PMC10007824 |
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Statistical analyses | Statistical analyses were done using the computer software SPSS for Mac OS version 26.0 (Statistical package for social Science, Armonk, NY, IBM Corp) at a significance level of 0.05. According to the Shapiro–Wilk normality test data were parametric ( | PMC10007824 |
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Results | PMC10007824 |
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Intragroup comparison | Comparisons between mean percentage of isthmus cleanliness before and after different activation techniques (comparison within the same group): The mean of isthmus cleanliness (%) changed significantly from i1 (after chemomechanical preparation) to i2 (after final irrigation) at all measured levels (2 mm, 4 mm, and 6 mm) and as a total. Total isthmus cleanliness (%) changed significantly (sign. < 0.001*) from 54.72 to 60.15 in the final needle irrigation without activation (NA) group, from 53.95 to 79.42 in the Irrisafe group and from 42.22 to 76.53 in the EDDY group as revealed by paired samples t-test (Table Comparison between mean % of anastomosis cleanliness before (i1) and after (i2) different activation techniques*significant at Comparison of mean % of isthmus cleanliness between different levels (comparison within the same group): showed that the intragroup comparison showed that improvement in anastomosis cleanliness (i2-i1) in the needle irrigation without activation group (NA) was significantly higher in the apical 2 mm level compared to the 4 & 6 levels. The difference in cleanliness improvement in the Irrisafe and EDDY was insignificant between the three levels. (Table | PMC10007824 |
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Discussion | tooth | ENLARGEMENT | The fundamental goal of root canal therapy is disinfection of the root canal system followed by proper coronal and apical sealing, while the role of shaping is to remove infected dentin and provide space for irrigant penetration and subsequent obturation. Irrigation during shaping does not eliminate half of the debris that accumulates throughout instrumentation especially in the apical third [The copper cube allowed the investigation of root cross sections at the different stages of root canal preparation and irrigation so that each tooth served as its own control for a true analysis of the change in anastomosis cleanliness [The major objective of this study was comparing the cleaning efficacy of different irrigation activation techniques per se. Therefore, a simple irrigation protocol with only NaOCl was chosen to eliminate the added effect of any chelating agents as justified in several previous studies [Roots were decoronated to standardize root length. This can be regarded as a technical limitation in this study because this allows easier access to the root canals, and there is no coronal reservoir of irrigation solution. Previous studies that focused on the prevalence of root canal isthmuses through different methodologies revealed high prevalence in mesiobuccal roots of maxillary molars and mesial roots of mandibular molars [Samples were analyzed under a stereomicroscope at 30 × magnification because it allowed clear visualization of both root canals and anastomoses in the same frame, in contrast to other studies that employed scanning electron microscope in which only limited areas of the section could be scanned [All the final irrigation techniques used in this study resulted in significant improvement in anastomosis cleanliness. As increasing the irrigant volume and activating it results in improved cleanliness [The least improvement in anastomosis cleanliness occurred in the control group (NA) (Figs. At the 4 mm and 6 mm levels, the difference between EDDY and PUI was insignificant. This can be attributed to the larger canal diameter at these levels, which allowed less-restricted vibration of both tips. This came in harmony with the previously published data comparing sonic to ultrasonic activation [Regarding the intragroup analysis of NA, the 2 mm level showed the highest CD. This can be explained by the fact that after cleaning and shaping, this area is the one with the most packed residual debris [PUI at the 2 mm level was less effective than 4 mm but similar to 6 mm without significant difference. This can be attributed to the narrowness of this area may results in a more file-to-wall contact than the middle. Some of the samples even showed signs of canal deformation due to the ultrasonic tip touching the walls while vibrating (Fig. It is important to emphasize that in this study, 1 mL of irrigant was activated for 30 s to investigate the exclusive effect of the activation technique. Increasing the irrigant volume, activation time, using a chelating agent and increasing the final apical enlargement size are considered limitations of the present study which may have different implications on the overall anastomosis cleanliness [ | PMC10007824 |
Acknowledgements | Not applicable. | PMC10007824 |
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Authors’ contributions | The first author run the experiment and wrote the main manuscript text. The second and third authors prepared the study design,figures and revised the whole manuscript. All authors contributed significantly to this study and have read and approved the submission of this manuscript to your journal for publication. | PMC10007824 |
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Funding | Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB). No financial support was granted for this study from any external source. | PMC10007824 |
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Availability of data materials | This data made available on reasonable request to the corresponding author. Also,This research article is available as a preprint on research square ( | PMC10007824 |
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Declarations | PMC10007824 |
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Ethics approval and consent to participate | All procedures performed were carried out in accordance with relevant guidelines, regulations and approved by the ethical committee of research of the Faculty of Dentistry, Suez Canal University (approval number for the study: 137/2018.) and all patients agreed on using their extracted teeth in research with a informed consent. | PMC10007824 |
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Consent for publication | Not applicable. | PMC10007824 |
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Competing interests | The authors deny any conflicts of interest related to this study. | PMC10007824 |
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References | PMC10007824 |
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Background | cancer | CANCER, CHRONIC DISEASES | Chemotherapy is associated with a wide range of physical and psychological side effects, so complementary and alternative therapies may be practiced as an independent treatment or combined with the standard ones to improve health-related quality of life of cancer patients. Laughter yoga has predominantly been used as a complementary therapy to enhance health and wellbeing of ordinary people and patients with chronic diseases. However, to date, few studies have evaluated the effects of this modern exercise on cancer patients undergoing chemotherapy in clinical settings, to the best of the authors’ knowledge. the present study aimed to investigate the effects of Laughter Yoga on the health-related quality of life of cancer patients undergoing chemotherapy. | PMC10259013 |
Methods | cancer, Cancer | ONCOLOGY, CANCER, CANCER | This study was a two-group randomized clinical trial on 69 cancer patients undergoing chemotherapy at Reza Radiotherapy and Oncology Center, Iran in 2018. Patients were randomly divided into intervention and control groups. The intervention group received laughter yoga for four sessions at one-week intervals. Each session consists of one part and lasts for 20–30 min. Patients’ health-related quality of life was assessed before and after the laughter yoga sessions using Quality of Life Questionnaire European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) version 3.0. SPSS Statistics (v.20 software was used to conduct Chi-square, independent t-test, Mann-Whitney, Wilcoxon and paired t-tests analyses of the data. | PMC10259013 |
Results | sleep disturbance, fatigue, pain | ADVERSE EVENTS, DISEASE | The number of participants in intervention and control groups were 34 and 35, there was no significant difference of demographic and disease related characteristics and pre-intervention HRQOL between two groups. In the intervention group, there is significant difference between pre- and post-intervention scores (Mean ± Standard Deviation) of emotional functioning (12.99 ± 10.49), physical functioning (0.78 ± 6.08), role functioning (3.43 ± 7.97), fatigue (-8.82 ± 22.01), pain (-8.33 ± 11.78), sleep disturbance (-15.68 ± 18.77), and global health and quality of life (6.37 ± 5.04) (p < 0.05). There was no significant change in the control group. Participants reported no adverse events. | PMC10259013 |
Conclusions | cancer | CANCER | A structured laughter yoga intervention in a hospital setting effectively improved health-related quality of life for cancer patients undergoing chemotherapy. Benefits to many patients could be expected if this would become a part of routine care. | PMC10259013 |
Trial Registration | This study was registered in the Iranian Registry of Clinical Trials (no. IRCT20180429039463N1) on 21/08/2018. | PMC10259013 |
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Supplementary Information | The online version contains supplementary material available at 10.1186/s12906-023-04028-2. | PMC10259013 |
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Keywords | PMC10259013 |
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Introduction | cancer, deaths, humor, Cancer | CANCER, CARDIOVASCULAR DISEASES, CANCER | Cancer accounts for 9% of all deaths across the world, and the second leading cause of mortality in developing nations following cardiovascular diseases [Laughter yoga is a type of complementary therapy which also incorporates some other components including mild type of physical exercises. This type of treatment combines unconditional laughter with yoga breathing practices and yoga stretching poses so that patients laugh different from jokes or humor programs [The purpose of this study was to determine the effect of laughter yoga on HRQOL in cancer patients undergoing chemotherapy. We hypothesized that implementing the laughter yoga program will significantly promote HRQOL in patients undergoing chemotherapy. | PMC10259013 |
Methods | PMC10259013 |
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O trial design | cancer | CANCER | This study was a single-center, two-group randomized clinical trial comparing the effects of structured laughter yoga program in cancer patients before chemotherapy. The study is reported using the CONSORT (Consolidated Standards of Reporting Trials) checklist. | PMC10259013 |
O participants | cancers, stomatitis, cancer, thrombocytopenia, upper gastrointestinal (UGI) cancer | CANCERS, STOMATITIS, CANCER, DISEASE, THROMBOCYTOPENIA, ONCOLOGY | The inclusion criteria were cancer patients with an age range of 18–60, having non-metastatic type of cancers, no auditory-visual problems, undergoing four sessions of chemotherapy per month, absence of stomatitis symptoms, no upper gastrointestinal (UGI) cancer, attending no simultaneous radiotherapy programs, as well as the mental and physical ability to perform laughter yoga. The exclusion criteria were chronic stress during the study approved by the psychologist of the center, disease exacerbation and the need for intensive care services, changes in chemotherapy programs due to thrombocytopenia or any other factors, and modifications in chemotherapy drug regimen. This study was a two-group randomized clinical trial on 69 cancer patients undergoing chemotherapy. It was conducted at the at Reza Radiotherapy and Oncology Center, Iran, in 2018. Patients were randomly divided into intervention and control groups., Mashhad, Iran, between October 2018 and June 2019. | PMC10259013 |
O intervention | cancer, Cancer | CANCER, CANCER | The intervention group received laughter yoga for four sessions with one-week intervals. Each session lasts for 20–30 min and it consists of 15 steps of laughter yoga performed consecutively. And each laugh lasts approximately 30 to 45 s. This intervention was provided by researchers who had completed laughter yoga training course from the laughter yoga instructor and participants were supervised during each session. Laughter yoga sessions were held in three groups of 8, 12, and 14 cancer patients. The intervention was carried out before the chemotherapy according to the protocol. The four sessions of the intervention were performed in a standing position following the 15 steps (Supplementary Material In the control group, only routine self-care training was conducted by the researchers in the meeting hall in the form of face-to-face education and the use of pamphlets. This program was implemented exactly the same for the intervention group with 10 min one session each week for four weeks. The educational content was developed after reviewing the related literature, up-to-date studies, guidelines of the National Cancer Prevention and Control Program published by the Ministry of Health and Medical Education (MHME), World Health Organization [ | PMC10259013 |
O outcomes | shortness of breath, nausea/vomiting, sleep disturbance, fatigue, diarrhea, cancer, pain, constipation, Cancer | APPETITE LOSS, CANCER, CANCER | The primary outcome of this trial was HRQOL, which was assessed using EORTC QLQ-C30 (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire version 3). Demographic information was also collected using a structured questionnaire.Demographic information questionnaire had 6 questions about age, frequency of chemotherapy, sex, type of cancer, previous chemotherapy experience, and experience of participating in program. This questionnaire was completed through an interview before the intervention.EORTC tool contained 30 items with five functioning domains, nine symptoms, and Global HRQOL status. HRQOL means subjective feeling of patients regarding their overall health and quality of life. The five functioning domains included physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning. The nine symptoms included fatigue, nausea/vomiting, pain, shortness of breath, sleep disturbance, appetite loss, constipation, diarrhea, and financial hardship. Raw score obtained from the rating given by the participants on questions was converted into transformed score ranging from zero to 100 as per the scoring manual. A higher value of HRQOL and functional scores, and lower value of symptoms and single items represents better health and wellbeing [The study questionnaires were completed before and after the laughter yoga sessions by the cancer patients, through interviews in a quiet room at the meeting hall next to the chemotherapy Center. First baseline demographic data were taken and initial assessment of HRQOL was done. Final assessment of HRQOL was done after four weeks, when laughter yoga intervention was delivered to the intervention group and self-care training education was given to the control group. Participants in both groups received their routine chemotherapy in between the assessments. | PMC10259013 |
O sample size and randomization | cancer | CANCER, BLIND | The sample size was determined by 34 patients in each group based on the results of a pilot study on 10 participants in each group using the comparison of two means formula with 95% confidence interval and 80% test power. Assuming the possibility of participants being lost to follow up loss of some cases, and to give more assurance to the completion of study with required sample size, 39 cancer patients in each group were included in the present study. Among them, five cases from the intervention group and four individuals from the controls were lost to follow up. Finally, 69 cancer patients remained in the study (Fig.
CONSORT Flow Chart of participantsThe first author of the study, as the research coordinator, referred to the chemotherapy unit and extracted the list of patients undergoing chemotherapy. Then introduced oneself to the cancer patients and selected eligible ones with reference to the mentioned criteria. The cancer patients were selected based on the convenience sampling method and then divided into the intervention and control groups using random sequence generated by the SPSS Statistics (v.20) software, kept in a closed envelope. Upon providing an individual oral explanation about the research objectives and methodology, informed written consent was obtained from the cancer patients in both groups. Although it is difficult to blind the participants in this trial, the outcome assessors and statisticians were blinded to the type of intervention. | PMC10259013 |
O statistical methods | cancer | CANCER | The data was analyzed using the SPSS Statistics (v.20) software total of 69 cancer patients out of 78 were included in the data analysis as nine cancer patients were lost to follow -up. Questionnaire was checked for completeness just after the participants returned it. The descriptive statistics (viz., frequency distribution, mean, and standard deviation) were used to describe and categorize the data. Inferential statistics including the Chi-square test, independent-samples t-test, and Mann-Whitney U test were used to test the research hypothesis. Wilcoxon signed-rank test and paired-samples t-tests were further employed for intra-group comparisons. The normality of the quantitative variables was correspondingly assessed by the Kolmogorov-Smirnov test. The significance level of 0.05 was set for all the tests in this study. | PMC10259013 |
Results | dyspnea, diarrhea, fatigue, appetite, constipation, pain | DISEASE, RECRUITMENT | 390 patients were assessed for eligibility. Once the desired sample size was reached, recruitment efforts ended. The 78 eligible candidates were randomly allocated into intervention (n = 39) and control (n = 39). The final number of participants available for comparison of baseline and flow up data was 69. The number of participants lost to follow up was 5 in the intervention group and 4 in control group. Thus, the number of participants in the final analysis was 34 in intervention group and 35 in control group (Fig. The majority of patients in the intervention (n = 22, 67.7%) and control (n = 24, 68.6%) groups were females. There was no significant difference between two groups in terms of other demographic and disease data (p > 0.05) (Table
General baseline characteristics of the participant’sSexN (%)Cancer typeN (%)Previous chemotherapy experienceN (%)Experience laughing yogaN (%)* Chi-square test **Exact Chi-square test ***Mann-Whitney U test ***Fisher’s exact testAt the pre-intervention stage, the mean scores of the physical function, role function, emotional function, cognitive function and social function in the intervention and control groups were not statistically significant (p > 0.05). But at at the post test the mean scores of the three functional domains such as physical functioning, role functioning and emotional functioning in the intervention group was significantly higher than that in the control group respectivly. It means that the mean scores of the physical functioning domain at the post-test in the intervention group (66.27 ± 17.59) was significantly higher than that in the control group (60.57 ± 18.81) (p < 0.05) Also mean scores of the role functioning domain in the intervention group (71.08 ± 25.06) was significantly higher than that in the control group (65 ± 76 ± 25.81) (p < 0.05). And emotional functioning domain in the intervention group (80.88 ± 16.60) was significantly higher than that in the control group (66.19 ± 26.19) (p < 0.05), (Table
Scores of functional domains of hetalth-related quality of life*Independent-samples t-test **Mann-Whitney U test ***Wilcoxon test ****Paired-samples t-testRegarding the symptoms and single items at baseline, the mean scores of the nausea/vomiting, fatigue, pain, dyspnea, sleep, appetite, constipation, diarrhea, financial and HRQOL (overall health and quality of life) in the intervention and control groups were not statistically significant (p > 0.05) At post-test, the mean scores of fatigue and pain in the intervention group were significantly lower than the control group (p < 0.05) (Table
Scores of symptoms and single items domains of health-related quality of life*Independent-samples t-test **Mann-Whitney U test ***Wilcoxon test ****Paired-samples t-testHRQOL means participants perspective on their overall health and quality of life | PMC10259013 |
Discussion | rheumatoid arthritis, sleep disturbance, fatigue, breast cancer, cancer, pain, increases pain | RHEUMATOID ARTHRITIS, CANCER, INFLAMMATION, BREAST CANCER | Our study shed light the effect of laughter yoga on HRQOL in cancer patients undergoing chemotherapy. The findings revealed that the implementation of the laughter yoga has improved the cancer patients HRQOL in terms of emotional functioning, role functioning, physical functioning, and overall HRQOL status. Laughter yoga had also reduced the symptoms of fatigue, pain, sleep disturbance, as well as nausea/vomiting. Implementing laughter yoga to the cancer patients undergoing chemotherapy in clinical settings by trained personnel thus might be helpful to alleviate their difficulties and enhance HRQOL.In a study in Japan, the findings had demonstrated that laughter accompanied by exercises had boosted emotional functioning in older adults. In the present study, laughter yoga had further augmented emotional functioning among the cancer patients thanks to their positive feelings and emotions, which could in turn have a positive effect on emotional functioning [Likewise, a four-session fun-laughter program in another study had been able to lower pain in patients with rheumatoid arthritis [In a study done in Turkey, six sessions of breathing exercises had reduced the incidence rate and severity of nausea/vomiting in breast cancer patients receiving chemotherapy [The possible mechanism of beneficial effect of laughter yoga seen in the interventional group could be due to the effect of laughter yoga on neurological, endocrine, and immune systems of human body. Laughter has shown to cause release of endorphins and dopamine, decrease of cortisol (stress hormone), and affects production of cytokines in the human body. These effect in turn enhances positive mood and sleep, modulates inflammation, and increases pain tolerance. The real or fake laughter is described to exert similar effect in the body [The present study had some limitations. Firstly, the positive effects observed could partly be due to different factors such as the social circumstances created for the laughter yoga intervention, the competency of the laughter yoga instructor, or due to the environment of hospital, or other patients related factors like the level of self-care, and the type of diet they used. Secondly, in the study, the intervention was administered in a moderate group of 8 to 14 participants, for about 20–30 min, and final outcome was assessed after four sessions. Likewise, the intervention was delivered to the patients undergoing chemotherapy and meeting all eligible criteria that consisted of the patients who could walk to do the laughter yoga in standing posture, further study may be needed to see the effects of laughter among the patients who are currently in wheel chair or in bed but still can laugh and do some physical movement and deep breathing, and on those patients who are using other treatment modalities. Finally, since the outcome measure is based on patient reported outcome as measured by structured tool, EORTC QLQ-C30, there can be chances of recall bias [ | PMC10259013 |
Conclusion | cancer, sleep disturbance, fatigue, pain | CANCER | This trial showed that a structured laughter yoga intervention program in a hospital setting delivered by trained instructor for 20–30 min each week for four weeks before chemotherapy effectively improve health-related quality of life of the cancer patients undergoing chemotherapy. This intervention showed enhancement of emotional functioning, improvement overall health and quality of life, and mitigation of fatigue, pain, and sleep disturbance symptoms. Many patients could be benefitted if laughter yoga is incorporated as a complementary therapy in routine clinical care practice. | PMC10259013 |
Acknowledgements | ONCOLOGY | The authors hereby extend their sincere gratitude to the heads of the Radiotherapy Center, the Oncology Center, the Psychology Center, the educational supervisor, the head nurse, and the nurses working at the Reza Radiotherapy and Oncology Center, Mashhad, Iran. | PMC10259013 |
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Authors’ contributions | MN, prepared the writing of the initial draft, acquisition of data, analyze and interpret the data, conceptualize the paper, and review and synthesize the literature. SRM, obtained funding for the manuscript, supervised, proof-read, and provided intellectual support in terms of statistical analysis and administrative, technical, and material support and supervised in the preparation of the manuscript. SM, supervised, proof-read, and provided intellectual support in terms of administrative, technical, and material support and supervised in the preparation of the manuscript. VL, provided critical review and significant revision of the manuscript for important intellectual content, proof-read, and supervised the preparation of the manuscript. All authors read and approved the final manuscript. | PMC10259013 |
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Funding | This study was a part of Master’s Thesis in Medical-Surgical Nursing with project code no. 970132. To carry out this study, Dr. Seyyed Reza Mazlum obtained a fund by the Vice-Chancellor’s Office for Research at Mashhad University of Medical Sciences, Mashhad, Iran. | PMC10259013 |
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Data Availability | The datasets generated in the present study are available from the corresponding author upon reasonable request. | PMC10259013 |
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Declarations | PMC10259013 |
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Ethics approval and consent to participate | cancer | ONCOLOGY, CANCER | The research was approved by the Research Ethics Committees of Mashhad University of Medical Sciences, Mashhad, Iran (no. IR.MUMS.NURSE.REC.1397.021). The approval was gained from the Director of Reza Radiotherapy and Oncology Center managers and head nurse. Before obtaining consent, researcher approached the patients and informed about the purpose, interventions, benefit, risk and outcome of the study. Upon obtained consent from the cancer patients, data was collected at baseline (before the intervention) and right after the last laughter yoga session. The questionnaire was administered by the same researcher. cancer patients were asked to respond to each item and upon completion, return this to the researcher. To maintain the confidentiality and privacy the identifying information was anonymized. The cancer patients were also informed that they can withdrew from the study at any time. All methods were performed in accordance with the relevant guidelines and regulations, which are aligned with the Declaration of Helsinki. | PMC10259013 |
Consent for publication | Not applicable. | PMC10259013 |
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Competing interests | The authors declare no competing interests. | PMC10259013 |
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Abbreviations | Health-related quality of lifeUpper gastrointestinalEuropean Organization for Research and Treatment of CancerMinistry of Health and Medical EducationWorld Health OrganizationGlobal health and quality of life | PMC10259013 |
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References | PMC10259013 |
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Abstract | PMC10274306 |
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Background and Aims | Ulcerative colitis, UC | DISEASE, ULCERATIVE COLITIS | Ulcerative colitis [UC] impacts patients’ health-related quality of life [HRQoL]. We assessed HRQoL and an exploratory patient-level composite endpoint (‘Comprehensive Disease Control’ [CDC]) in individuals receiving filgotinib [an oral JAK1 preferential inhibitor] in the SELECTION trial. | PMC10274306 |
Methods | UC | REMISSION, RECTAL BLEEDING | In SELECTION [NCT02914522], a double-blind, randomized, placebo-controlled, phase 2b/3 trial, adults with moderately to severely active UC received once-daily filgotinib 200 mg, filgotinib 100 mg or placebo for 11 weeks in Induction Study A [biologic-naïve] or B [biologic-experienced]. Filgotinib responders [week 10 clinical remission/response] were re-randomized to their filgotinib regimen or placebo for the 48-week Maintenance Study. We assessed week 10 and week 58 SF-36, EQ-5D, WPAI and IBDQ scores. Achievement of CDC (patient-level partial Mayo Clinic Score [pMCS] remission [pMCS ≤2, no individual rectal bleeding, stool frequency or physician’s global assessment subscore >1], endoscopic improvement [endoscopic subscore ≤1], faecal calprotectin <150 µg/g and IBDQ score ≥170) and its association with HRQoL and histological outcomes were also explored. | PMC10274306 |
Results | Analyses included 382 biologic-naïve and 404 biologic-experienced patients. Filgotinib 200 mg induced and maintained improvements vs placebo in SF-36, EQ-5D, WPAI and IBDQ scores, and restored HRQoL by week 10. Proportionally more filgotinib 200 mg- than placebo-treated patients achieved CDC at weeks 10 and 58 [ | PMC10274306 |
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Conclusions | DISEASE | Filgotinib 200 mg results in short- and long-term improvements in HRQoL. High-level improvement of HRQoL relates to a stringent composite endpoint suggesting meaningful disease control in a subset of filgotinib-treated individuals.ClinicalTrials.gov identifier: NCT02914522 | PMC10274306 |
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1. Introduction | inflammatory bowel disease of the colonic mucosa, Ulcerative colitis, UC | ULCERATIVE COLITIS | Ulcerative colitis [UC] is an inflammatory bowel disease of the colonic mucosa that negatively affects patients’ health-related quality of life [HRQoL].Patients consider the ability to improve HRQoL to be among the most important attributes of a UC treatment.Filgotinib is an oral Janus kinase [JAK] 1 preferential inhibitor that has been approved in the European Union and the UK for the treatment of adults with moderately to severely active UC.In these exploratory and | PMC10274306 |
2. Materials and Methods | PMC10274306 |
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2.1. Overall study design | SELECTION [NCT02914522] was a combined phase 2b/3 double-blind, randomized, placebo-controlled trial comprising two induction studies and a Maintenance Study. Details of the study design have been previously described by Feagan | PMC10274306 |
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2.2. Pre-specified exploratory analyses | As part of pre-specified exploratory analyses of SELECTION, changes from induction/maintenance baseline in the following outcomes were assessed at weeks 10 and 58: generic HRQoL, as measured by SF-36 physical component summary [PCS], mental component summary [MCS] and subscale scores, as well as EQ-5D visual analogue scale [VAS] and EQ-5D 5-level [-5L] UK utility scores; and disease-specific HRQoL, as measured by IBDQ total score and subscores. | PMC10274306 |
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2.3.
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2.3.1. Achievement of MCIDs in HRQoL outcomes | presenteeism | The proportions of patients achieving the minimal clinically important difference [MCID] in the following measures at weeks 10 and 58 were assessed: SF-36 PCS score, SF-36 MCS score, EQ-5D VAS score, EQ-5D UK utility score, IBDQ total score, combined IBDQ and SF-36 scores [achievement of the MCID in each of IBDQ total score, SF-36 PCS score, and SF-36 MCS score], and WPAI activity impairment score. In addition, the proportions of patients who were in employment at induction baseline and who achieved the MCID in WPAI absenteeism, presenteeism and work productivity loss scores were assessed at weeks 10 and 58. EQ-5D-5L values were standardized to the EQ-5D 3-level [-3L] according to the algorithm proposed by van Hout | PMC10274306 |
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2.3.2. Restoration of SF-36-defined HRQoL | SF-36 scores relative to age–sex norms were examined. The proportions of patients with an SF-36 PCS or MCS score <40 at induction baseline who achieved restored SF-36-defined HRQoL [SF-36 PCS or MCS score ≥40] | PMC10274306 |
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2.3.3. Assessment of individual patient treatment benefits: achievement of an exploratory composite endpoint, CDC | REMISSION, RECTAL BLEEDING | The proportion of patients who achieved CDC, comprising four established treatment outcomes, was assessed at weeks 10 and 58. Patients were considered to have achieved CDC if they achieved: (1) partial Mayo Clinic Score [pMCS] remission [pMCS ≤2 and no individual rectal bleeding, stool frequency or physician’s global assessment subscore >1]; (2) endoscopic improvement [Mayo endoscopic subscore of 0 or 1]; (3) inflammatory biomarker remission [faecal calprotectin <150 µg/g] | PMC10274306 |
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2.4. Statistical analyses | REGRESSION, REMISSION | These analyses were conducted using the SELECTION induction and maintenance full analysis sets.Patient demographics and baseline characteristics were analysed using descriptive statistics. Changes from induction baseline to week 10 and from maintenance baseline to week 58 were calculated for each HRQoL measure using least-squares [LS] mean changes with 95% confidence intervals [CIs]. Differences in LS mean changes were estimated using analysis of covariance adjusted for baseline HRQoL measures and stratification factors. Treatment assignments and analyses were stratified in Induction Study A by day 1 use of oral systemic corticosteroids and use of immunosuppressants [6-mercaptopurine, azathioprine and methotrexate]; in Induction Study B, by the same factors as in Induction Study A, and by previous exposure to one vs more than one biologic; and in the Maintenance Study, by the same factors as in Induction Study A, and by participation in Induction Study A or B. Binary assessment of the proportion of patients achieving the MCID in each of the HRQoL measures at weeks 10 and 58 was performed using Cochran–Mantel–Haenszel tests. No adjustment for multiple comparisons was made. A logistic regression model was used to calculate odds ratios with 95% CIs for restoration of SF-36-defined HRQoL at week 10 and maintenance of normal SF-36-defined HRQoL at week 58 for filgotinib 200 mg compared with placebo. The proportions of patients who achieved CDC at weeks 10 and 58, and the proportions of patients who had minimal clinically important improvements and declines in HRQoL measures from induction baseline to week 10 and from maintenance baseline to week 58, respectively, among CDC achievers and non-achievers, were compared using Pearson’s chi-squared test.All missing data were imputed using a last observation carried forward approach, except for the proportions of patients in IBDQ remission, for which non-responder imputation was used. Because these were exploratory and | PMC10274306 |
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3. Results | PMC10274306 |
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3.1. Patient disposition and baseline characteristics | INFLAMMATORY BOWEL DISEASE, DISEASE CHARACTERISTIC, ULCERATIVE COLITIS | These analyses included 382 and 404 patients from Induction Studies A and B, respectively, and 297 patients from the Maintenance Study. Patient baseline demographic and disease characteristics were similar between treatment groups within each induction study [Baseline demographics and characteristics of patients in Induction Studies A and B
EQ-5D, EuroQol 5-dimension; EQ-5D-5L, EuroQol 5-dimension 5-level; hsCRP, high-sensitivity C-reactive protein; IBDQ, Inflammatory Bowel Disease Questionnaire; MCS, mental component summary; PCS, physical component summary; SD, standard deviation; SF-36, 36-Item Short-Form Survey; UC, ulcerative colitis; VAS, visual analogue scale; WPAI, Work Productivity and Activity Impairment questionnaire. | PMC10274306 |
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3.2. Primary HRQoL analyses | PMC10274306 |
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3.2.1. SF-36 | INFLAMMATORY BOWEL DISEASE | At week 10, patients who had received filgotinib 200 mg had greater LS mean increases from induction baseline in SF-36 PCS and MCS scores than those who had received placebo [Proportions of patients achieving the MCID in SF-36, EQ-5D, WPAI and IBDQ total scores in Induction Studies A and B at week 10 and in the Maintenance Study at week 58
CI, confidence interval; EQ-5D, EuroQol 5-dimension; EQ-5D-5L, EuroQol 5-dimension 5-level; HRQoL, health-related quality of life; IBDQ, Inflammatory Bowel Disease Questionnaire; MCID, minimal clinically important difference; SF-36, 36-Item Short-Form Survey; VAS, visual analogue scale; WPAI, Work Productivity and Activity Impairment questionnaire.Change in SF-36 PCS [A, B], SF-36 MCS [C, D], EQ-5D VAS [E, F], EQ-5D-5L UK utility [G, H] and IBDQ total [I, J] scores in Induction Studies A and B at week 10. Error bars indicate 95% CIs. CI, confidence interval; EQ-5D, EuroQol 5-dimension; EQ-5D-5L, EuroQol 5-dimension 5-level; IBDQ, Inflammatory Bowel Disease Questionnaire; LS, least-squares; MCS, mental component summary; PCS, physical component.At week 58, patients in the filgotinib 200 mg group had LS mean increases from maintenance baseline in SF-36 PCS and MCS scores, whereas patients in the respective placebo group had LS mean decreases in the same measures [Change in SF-36 PCS [A], SF-36 MCS [B], EQ-5D VAS [C], EQ-5D-5L UK utility [D] and IBDQ total [E] scores in the Maintenance Study at week 58. Error bars indicate 95% CIs. CI, confidence interval; EQ-5D, EuroQol 5-dimension; EQ-5D-5L, EuroQol 5-dimension 5-level; IBDQ, Inflammatory Bowel Disease Questionnaire; LS, least-squares; MCS, mental component summary; PCS, physical component summary; SF-36, 36-Item Short-Form Survey; VAS, visual analogue scale.In a further analysis, we assessed restoration of HRQoL as measured using SF-36 scores. Among patients with an SF-36 PCS or MCS score of <40 at induction baseline, a greater proportion of those treated with filgotinib 200 mg than those treated with placebo achieved restoration of SF-36-defined HRQoL [SF-36 PCS or MCS score ≥40] by week 10 in the biologic-naïve and biologic-experienced populations [all | PMC10274306 |
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3.2.2. EQ-5D | At week 10, filgotinib 200 mg-treated patients had a greater LS mean increase from induction baseline in EQ-5D VAS and EQ-5D-5L UK utility scores than placebo-treated patients, in both the biologic-naïve and biologic-experienced populations [all At week 58, patients in the filgotinib 200 mg group experienced LS mean increases from maintenance baseline in EQ-5D VAS and EQ-5D-5L UK utility scores, whereas patients in the respective placebo group experienced LS mean decreases [EQ-5D VAS, | PMC10274306 |
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3.2.3. WPAI | Greater proportions of patients who received filgotinib 200 mg than those who received placebo achieved the MCID in WPAI activity impairment score at week 10 [biologic-naïve, | PMC10274306 |
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3.2.4. IBDQ | REMISSION | At week 10, filgotinib 200 mg-treated patients had a greater LS mean increase from induction baseline in IBDQ total score than placebo-treated patients (biologic-naïve: 51 vs 30 points, Δ 21 [95% CI, 13, 28], At week 58, patients in the filgotinib 200 mg group experienced an LS mean increase from maintenance baseline in IBDQ total score of 5 points, compared with a 9-point decrease in patients in the respective placebo group [IBDQ remission was achieved by greater proportions of filgotinib 200 mg-treated than placebo-treated patients at week 10 [biologic-naïve, 55.9% vs 35.0%; biologic-experienced, 43.1% vs 17.6%; both | PMC10274306 |
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3.3. Secondary HRQoL analyses | PMC10274306 |
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3.3.1. Proportions of patients achieving CDC | INFLAMMATORY BOWEL DISEASE, REMISSION, DISEASE | To assess the treatment benefits of filgotinib 200 mg in individuals, we evaluated the proportions of patients who achieved the exploratory composite endpoint, CDC [comprising pMCS remission, endoscopic improvement, inflammatory biomarker remission and IBDQ remission] at weeks 10 and 58. In the overall induction population, CDC was achieved by greater proportions of filgotinib 200 mg-treated than placebo-treated patients [10.9% vs 2.9%, Proportions of patients achieving CDC and its component outcomes in Induction Studies A and B at week 10 and in the Maintenance Study at week 58
CDC, Comprehensive Disease Control; CI, confidence interval; HRQoL, health-related quality of life; IBDQ, Inflammatory Bowel Disease Questionnaire; pMCS, partial Mayo Clinic Score. | PMC10274306 |
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3.3.2. Proportions of patients experiencing minimal clinically important improvements and declines in HRQoL and work productivity measures by CDC achievement | INFLAMMATORY BOWEL DISEASE, REMISSION, DISEASE | To evaluate the association between CDC achievement and HRQoL, we assessed clinically important improvements from induction baseline to week 10, and clinically important declines from maintenance baseline to week 58, in generic HRQoL and work productivity outcomes. Greater proportions of patients who achieved CDC at week 10 than those who did not achieve CDC experienced minimal clinically important improvements from induction baseline in the following measures: SF-36 PCS, SF-36 MCS and all SF-36 subscale scores, EQ-5D VAS and EQ-5D-5L UK utility scores, and WPAI activity impairment score [all Proportions of patients who experienced minimal clinically important improvements from induction baseline to week 10 and minimal clinically important declines from maintenance baseline to week 58 in SF-36, EQ-5D and WPAI scores, among CDC achievers and non-achievers
CDC was defined as achievement of pMCS remission, endoscopic improvement, inflammatory biomarker remission and IBDQ remission.CDC, Comprehensive Disease Control; EQ-5D, EuroQol 5-dimension; EQ-5D-5L, EuroQol 5-dimension 5-level; HRQoL, health-related quality of life; IBDQ, Inflammatory Bowel Disease Questionnaire; MCID, minimal clinically important difference; MCS, mental component summary; PCS, physical component summary; pMCS, partial Mayo Clinic Score; SF-36, 36-Item Short-Form Survey; VAS, visual analogue scale, WPAI, Work Productivity and Activity Impairment questionnaire. | PMC10274306 |
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3.3.3. Proportions of patients in histological remission among CDC achievers vs non-achievers | INFLAMMATORY BOWEL DISEASE, DISEASE, REMISSION, DISEASE | To assess the relationship between achievement of CDC and histomorphology [as an objective marker of disease activity], the proportions of patients who did and did not achieve CDC who were in histological remission were investigated. At week 10, greater proportions of CDC achievers than non-achievers were in histological remission [biologic-naïve: 75.5% vs 21.4%; biologic-experienced: 57.1% vs 14.2%; both Proportions of CDC achievers and non-achievers in histological remission in Induction Studies A and B [A–C] at week 10, and in the Maintenance Study at week 58 [D]. CDC was defined as achievement of pMCS remission, endoscopic improvement, inflammatory biomarker remission and IBDQ remission. Histological remission was defined as a grade 0 Geboes score of ≤0.3, grade 1 score of ≤1.1, grade 2A score of ≤2A.3, grade 2B score of 2B.0, grade 3 score of 3.0, grade 4 score of 4.0 and grade 5 score of 5.0. CDC, Comprehensive Disease Control; IBDQ, Inflammatory Bowel Disease Questionnaire; pMCS, partial Mayo Clinic Score. | PMC10274306 |
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4. Discussion | filgotinib, UC | DISEASE, REMISSION, DISEASE COURSE | This study assessed the effects of treatment with filgotinib on generic and disease-specific HRQoL, and work productivity in patients with UC in the SELECTION trial. Moreover, to examine the effect of filgotinib at the patient level, we developed and evaluated a four-component composite endpoint, CDC. Treatment with filgotinib 200 mg resulted in improvements in generic and disease-specific HRQoL in the short term [10 weeks] among both biologic-naïve and biologic-experienced patients, with improvements maintained during long-term treatment [58 weeks]. In addition, filgotinib 200 mg treatment was effective in restoring patients’ HRQoL as measured by SF-36 scores to that of the general population after 10 weeks of treatment.Patients consider the ability to improve HRQoL to be among the most important attributes of a UC treatment.Restoration of HRQoL is now among the long-term treatment targets recommended for UC.Treatment differences in HRQoL improvements at week 10 were numerically larger in biologic-experienced than biologic-naïve patients, despite the former group having a lower response rate [53.1% and 66.5% of biologic-experienced and biologic-naïve filgotinib 200 mg-treated patients achieved an MCS response at week 10, respectivelyTo assess the benefits of filgotinib 200 mg at the patient level, we combined endpoints that are treatment targets specified by the STRIDE-II guidelines,Limitations of these analyses include that HRQoL measures were assessed at only two time points. Future studies could assess individual patient trajectories using multiple endpoint data at various time points [from the beginning of treatment through to CDC], in order to evaluate disease burden and fluctuations over time, and to determine early indicators of a positive/negative disease course. A further limitation was that only responders entered the Maintenance Study, owing to the re-randomization trial design. This introduces bias due to the exclusion of non-responders. Nevertheless, this was not considered a major issue, as the purpose of the maintenance phase was to evaluate the perpetuation of previously identified therapeutic benefit arising from the induction phase. It is also worth noting that for the group who received induction filgotinib and maintenance placebo, as noted above, it cannot be ruled out that priming with filgotinib impacted the disease trajectory during maintenance when filgotinib treatment ceased. However, if anything this is likely to favour an underestimation of the benefits of filgotinib. In addition, this is a study design that is frequently employed in UC trials as it allows for evaluation of different treatment durations whilst minimizing the time that any individual patients spend on the placebo. This is important as withholding of favourable care would present ethical issues.Analyses evaluating the composite endpoint were exploratory and require formal external validation, for example reliability testing. This is particularly true considering the response to filgotinib of inflammatory biomarkers. These are well-established indicators of active disease, as well as being the least invasive of all the objective endpoints, and the lack of concordance of their profiles with other disease markers warrants further investigation. Alternatively, our data could suggest the threshold for inflammatory biomarker remission could be made less stringent, given that clinically significant improvements to HRQoL and endoscopic improvement were achieved in this study without the criterion for inflammatory biomarker remission being met. Nevertheless, it could be speculated that assessment of multiple established UC outcomes within a composite endpoint may be valuable for clinicians managing patients with UC, as treatment shifts towards a more personalized and patient-centred approach. | PMC10274306 |
4.1. Conclusions | REMISSION | Based upon data from the SELECTION trial, filgotinib 200 mg resulted in short- and long-term improvements in generic and disease-specific HRQoL. Filgotinib 200 mg led to some patients achieving a stringent exploratory composite endpoint that may be associated with both improved HRQoL and histological remission. Further work is required to validate this exploratory endpoint. | PMC10274306 |
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Supplementary Material | Click here for additional data file. | PMC10274306 |
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Acknowledgments | We thank Ken Hasegawa [Gilead Sciences Inc.] for his contributions to the primary data analysis. Medical writing support for the preparation of the manuscript was provided by Frances Thompson, PhD, of PharmaGenesis London, London, UK, and funded by Galapagos NV [Mechelen, Belgium]. | PMC10274306 |
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Funding | This work (i.e. the SELECTION trial) was supported by Gilead Sciences Inc. Galapagos NV was a collaborator for the SELECTION trial and funded this analysis. | PMC10274306 |
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Conflict of Interest | Janssen, Johnson & Johnson,, IBD | S.S. reports speaker/consultancy fees from AbbVie, Advanced Molecular Transport, Amgen, Bristol Myers Squibb [BMS], Boehringer Ingelheim, Falk, Ferring Pharmaceuticals, Galapagos/Gilead, Genentech/Roche, Janssen, Merck/MSD, Pfizer, Prometheus and Takeda. B.G.F. reports grants and personal fees from AbbVie, Amgen, AstraZeneca, BMS, Janssen Biotech/Centocor, Johnson & Johnson/Janssen, Pfizer, Receptos and Takeda; personal fees from Ablynx, ActoGeniX, AdMIRx Inc., Akebia Therapeutics Inc., Allergan, Atlantic Pharma, Avaxia Biologics Inc., Avir Pharma, Baxter Healthcare Corporation, Biogen Idec, BiomX Israel, Boehringer Ingelheim, Boston Pharmaceuticals, Calypso Biotech, Celgene, Elan/Biogen, enGene, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, gIcare Pharma, Gilead, Given Imaging, Gossamer Pharma, GSK, Inception IBD Inc., Ironwood, Japan Tobacco Inc., Kyowa Hakko Kirin Co. Ltd, Lexicon, Lilly, Lycera Biotech, Merck, Mesoblast Pharma, Millennium Pharmaceuticals, Nestlé, Nextbiotix, Novartis, Novo Nordisk, Par’Immune, Progenity, Prometheus Therapeutics and Diagnostics, Protagonist, Qu Biologics, Salix Pharmaceuticals, Shire, Sienna Biologics, Sigmoid Pharma, Synergy Pharma, Teva Pharmaceuticals, TiGenix, Tillotts, UCB, Vertex, VHsquared, Vivelix Pharmaceuticals, Wyeth, Zealand Pharma and Zyngenia; and is the Senior Scientific Director of Alimentiv Inc. and a Professor of Medicine at Western University. L.P.B. reports personal fees from AbbVie, Allergan, Amgen, Arena, Biogen, BMS, Celgene, Celltrion, Enthera, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, Index Pharmaceuticals, Inotrem, Janssen, Lilly, MSD, Mylan, Norgine, OSE Immunotherapeutics, Pandion Therapeutics, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Theravance, Thermo Fisher, Tillotts, Viaris, and Vifor; grants from AbbVie, Fresenius Kabi, MSD and Takeda; and stock options from CTMA. S.V. reports grants from AbbVie, Galapagos, Johnson & Johnson, Pfizer and Takeda, and consultancy fees from AbbVie, Abivax, Arena Pharmaceuticals, Avaxia, Boehringer Ingelheim, Celgene, Dr Falk Pharma, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, Gilead, GSK, Hospira, Janssen, Mundipharma, MSD, Pfizer, ProDigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Takeda, Theravance and Tillotts Pharma AG. M.F., K.H. and A.O. are employees and shareholders of Galapagos NV. H.P. was an employee and shareholder of Galapagos NV at the time of the study. P.D. is an employee of Cytel Health Canada, which received funding from Galapagos NV to conduct the analysis. S.D. reports personal fees from AbbVie, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring Pharmaceuticals, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB Inc. and Vifor. | PMC10274306 |
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Author Contributions | M.F., K.H., A.O. and H.P. contributed to study design. S.S., B.G.F., L.P.B., S.V. and S.D. contributed to data collection. M.F. and P.D. contributed to data analysis. All authors contributed to data interpretation. All authors contributed to the development of the manuscript and all authors approved the final version. All authors agree to be accountable for all aspects of the work. | PMC10274306 |
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Data Availability | Colitis, Crohn’s | COLITIS | Anonymized individual patient data will be shared upon request for research purposes dependent upon the nature of the request, the merit of the proposed research, the availability of the data and its intended use. The full data sharing policy for Gilead Sciences, Inc., can be found at Part of this work was presented at the European Crohn’s and Colitis Organisation (ECCO) 2022 congress (virtual congress). | PMC10274306 |
References | PMC10274306 |
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Background | depression, post-traumatic stress disorder, co-occurring mental health disorders | DISORDER, DISORDERS | Identifying patients in primary care services with opioid use disorder and co-occurring mental health disorders is critical to providing treatment. Objectives of this study were to (1) assess the feasibility of recruiting people to screen in-person for opioid use disorder and co-occurring mental health disorders (depression and/or post-traumatic stress disorder) in primary care clinic waiting rooms in preparation for a randomized controlled trial, and (2) compare results of detecting these disorders by universal in-person screening compared to electronic health record (EHR) diagnoses. | PMC9881516 |
Methods | co-occurring mental health disorders | DISORDER, RECRUITMENT | This cross-sectional feasibility and pilot study recruited participants from four primary care clinics, two rural and two urban, from three health care organizations in New Mexico. Inclusion criteria were adults (≥ 18 years), attending one of the four clinics as a patient, and who spoke English or Spanish. Exclusion criteria were people attending the clinic for a non-primary care visit (e.g., dental, prescription pick up, social support). The main outcomes and measures were (1) recruitment feasibility which was assessed by frequencies and proportions of people approached and consented for in-person screening, and (2) relative differences of detecting opioid use disorder and co-occurring mental health disorders in waiting rooms relative to aggregate EHR data from each clinic, measured by prevalence and prevalence ratios. | PMC9881516 |
Results | depression, opioid use disorder, post-traumatic stress disorder, co-occurring mental health disorders | DISORDER | Over two-weeks, 1478 potential participants were approached and 1145 were consented and screened (77.5% of patients approached). Probable opioid use disorder and co-occurring mental health disorders were identified in 2.4% of those screened compared to 0.8% in EHR. Similarly, universal screening relative to EHR identified higher proportions of probable opioid use disorder (4.5% vs. 3.4%), depression (17.5% vs. 12.7%) and post-traumatic stress disorder (19.0% vs. 3.6%). | PMC9881516 |
Conclusions | depression, post-traumatic stress disorder | DISORDER, DISORDERS | Universal screening for opioid use disorder, depression, and post-traumatic stress disorder was feasible, and identified three times as many patients with these co-occurring disorders compared to EHR. Higher proportions of each condition were also identified, especially post-traumatic stress disorder. Results support that there are likely gaps in identification of these disorders in primary care services and demonstrate the need to better address the persistent public health problem of these co-occurring disorders. | PMC9881516 |
Supplementary Information | The online version contains supplementary material available at 10.1186/s13722-023-00362-5. | PMC9881516 |
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Keywords | PMC9881516 |
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Background | co-occurring mental health disorders, depression, OUD, pain, post-traumatic stress disorder, PTSD, SUDs, Depression | DISORDER, RECRUITMENT, DISORDERS | Mental health disorders often co-occur with substance use disorders (SUDs), especially opioid use disorder (OUD), and are often untreated [Depression, unhealthy drug use, and post-traumatic stress disorder (PTSD) are all common disorders in patients who receive care in PC settings [Co-occurring PTSD and OUD is common but difficult to treat. Poor treatment outcomes may be due to the lack of treatment models that can address both problems simultaneously [We implemented a feasibility and pilot study to assess identification of probable OUD and co-occurring mental health disorders in family practice clinics in New Mexico via universal screening in waiting rooms. The main objectives were to (1) assess the feasibility of implementing universal screening to identify probable OUD, depression, and PTSD among patients in PC clinics to inform recruitment operations for a planned clinical trial, and (2) assess the likelihood of waiting room screening for detecting probable OUD and co-occurring mental health disorders (“observed”) by comparing to electronic health record diagnoses (EHR, “expected”) during the same period. We hypothesized that universal screening in PC for probable OUD and co-occurring mental health disorders would yield a higher number of patients with these disorders relative to what is recorded in the EHR. An exploratory goal was to assess patients’ reports of treatments received for any of these disorders. As pain is often associated with chronic opioid use, OUD, PTSD, and depression [ | PMC9881516 |
Methods | PMC9881516 |
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Study design and setting | OUD, depressive disorder, PTSD, MDD, depression | RECRUITMENT | We administered a cross-sectional survey within four family-practice clinics from three healthcare organizations in New Mexico. Two clinics were located within the Albuquerque city limits and two were in rural areas in Central and Southwestern counties. Three of the clinics were classified as Federally Qualified Health Centers (FQHCs) and the fourth clinic was part of an academic medical center. From October 2018 to September 2019, the clinics saw between 2850 and 5960 unique patients per year. Data for this pilot study were collected in February and March 2020, prior to the SARS-CoV-2 pandemic. We assessed feasibility of recruitment by assessing the number and proportion of people approached for screening and the number and percent of those who consented to screen. The primary objective was to assess identification of probable OUD with probable co-occurring depression and/or PTSD in observed survey data from waiting room screening versus clinical data obtained from the EHR (expected), as well as for each condition individually. ICD-10 codes for diagnoses of OUD, major depressive disorder (MDD), and PTSD were used to identify patients in the EHR during the study period. For these patients, we obtained data related to behavioral health treatment from CPT codes and data on medications prescribed for OUD (Additional File | PMC9881516 |
Participants and procedures | Over a two-week study period, research assistants approached people in each of the clinic waiting rooms to screen for eligibility. Adults, ages 18 and older, attending one of the four clinics as a patient, and who spoke English or Spanish were considered eligible and approached. Potential participants were told, “ | PMC9881516 |
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Measures | depression, OUD, PTSD | ABUSE | Two sources of data were used for this study: aggregate data from each clinic’s EHR and the survey data from waiting room patients. EHR data included: total number of visits, total number of unique patients, and numbers of unique patients with OUD, depression, or PTSD as well as more than one of these diagnoses. We obtained counts from the clinics’ EHRs over a 1-year period (October 1, 2018 – September 30, 2019). Additionally, the clinics provided the aggregate number of unique adult patient PC visits during each clinic’s two-week study period.In the universal screening survey, probable OUD was screened for using items adapted from the myTAPS screener, a self-administered version of the National Institute on Drug Abuse Tobacco, Alcohol, Prescription medication and other Substance use (TAPS) screener [ | PMC9881516 |
Statistical analyses | pain | Descriptive statistics from survey responses were calculated for age, gender, language preference, clinic attendance, and pain experience. Aggregate data over the 1-year period from the EHR records was obtained for each clinic and combined. These counts were divided by 26 for an average 2-week estimate for comparability to the waiting room survey data collection period. Medians, 25th and 75th percentiles (Q1 and Q3, respectively), and frequencies and percentages were calculated to summarize data. Prevalence estimates and 95% confidence intervals (CIs) were calculated for the survey responses and EHR samples. Prevalence ratios comparing the survey to EHR estimates and corresponding 95% CIs were calculated. | PMC9881516 |
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Results | PMC9881516 |
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Discussion | depression, OUD, co-occurring mental health disorders, PTSD | DISORDERS | Overall, in-person screening identified a nearly three-fold higher proportion of patients (2.4%) with probable OUD and co-occurring mental health disorders compared to the EHR (0.8%). We also identified a higher proportion of each condition separately (OUD, depression, and PTSD) with the survey. To our knowledge the prevalence of OUD and co-occurring mental health disorders has not been quantified and compared using a universal screening approach in primary care clinics in other studies. It is not surprising that EHR data would underestimate these conditions as patients may not disclose symptoms or problems to providers in association with discomfort, poor help-seeking intention, trust, shame, or stigma [Our study also found large variability in treatment for OUD and co-occurring mental health disorders relative to probable diagnoses. In the universal screening sample, among those with probable OUD and co-occurring mental health disorders, almost half (46.2%) reported not receiving any treatment, and only one in five participants was receiving both medication and counseling for at least one of the conditions. Other studies have also shown low rates of treatment for OUD in PC clinics [Our results also show missed opportunities for universal screening of probable OUD and co-occurring mental health disorders in PC. Currently, the USPSTF recommends routine screening of adults for depression [This study has several potential limitations including the cross-sectional design and self-reported data obtained from universal screening. Recall and reporting bias can occur when assessing sensitive conditions, resulting in underestimation of the prevalence estimates. However, since the survey was anonymous this limitation may have been minimized. The consistency of our results showing significant differences in observed versus expected prevalence of disorders also suggests that reporting bias was low. Our sample is not likely to be representative of PC patient populations in other locations; it was limited to English and Spanish speaking patients at PC clinics in New Mexico, three of which were FQHCs. Strengths of the results include the relatively large number of patients accessed over the 2-week survey period and the use of validated screening instruments. While our research assistants reached approximately 45% of adults visiting the primary care clinics, we demonstrated acceptability of the screening questions via the high completion rate (93.9%). Assessing these conditions without anonymizing questions and providing results to the primary care provider has potential to be effective. The participating clinics in this study have a strong community presence and have a known positive, non-judgmental approach to substance use, substance use treatment, and mental health; qualities that could enhance self-reporting. One approach could be with self-administered screeners given to every patient at check-in on a regular basis. For example, the PHQ-9 is already administered to every patient at these study clinics on an annual basis. | PMC9881516 |
Conclusions | OUD, co-occurring mental health disorders | DISORDERS | This study helps quantify the potential extent of diagnostic and treatment service gaps for OUD and co-occurring mental health disorders in PC settings serving rural and socioeconomically disadvantaged patients in New Mexico. Rates of these disorders in these settings are generally higher than what is documented in the EHR (as seen in this study and in previous studies in PC and integrated health systems) [ | PMC9881516 |
Acknowledgements | opioid use disorder, co-occurring mental health disorders | The study is named Collaboration Leading to Addiction Treatment and Recovery from Other Stresses (CLARO Study). The CLARO Study Group includes the PIs and Co-Investigators, key staff (such as project directors and patient representatives), and key stakeholders. The authors appreciate the CLARO partnerships with First Choice Community Healthcare, Hidalgo Medical Services, and the University of New Mexico Health System. We acknowledge the clinicians and research staff who supported the study. We also acknowledge Michael Schoenbaum, Ph.D., from the National Institute of Mental Health and the Science Officer for U01MH121954. We thank all of the participants who provided information to help advance care and treatment of opioid use disorder and co-occurring mental health disorders. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. | PMC9881516 |
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