Chronic low back pain (CLBP) is the most common chronic pain condition worldwide. Currently, primary care physiotherapy is one of the main treatment options, but effects of this treatment are small. Virtual Reality (VR) could be an adjunct to physiotherapy care, due to its multimodal features. The primary aim of this study is to assess the (cost-)effectiveness of physiotherapy with integrated multimodal VR for patients with complex CLBP, compared to usual primary physiotherapy care.A multicenter, two-arm, cluster randomized controlled trial (RCT) including 120 patients with CLBP from 20 physiotherapists will be conducted. Patients in the control group will receive 12 weeks of usual primary physiotherapy care for CLBP. Patients in the experimental group will receive treatment consisting of 12 weeks of physiotherapy with integrated, immersive, multimodal, therapeutic VR. The therapeutic VR consists of the following modules: pain education, activation, relaxation and distraction. The primary outcome measure is physical functioning. Secondary outcome measures include pain intensity, pain-related fears, pain self-efficacy and economic measures. Effectiveness of the experimental intervention compared to the control intervention on primary and secondary outcome measures will be analyzed on an intention-to-treat principle, using linear mixed-model analyses.This pragmatic, multicenter cluster randomized controlled trial, will determine the clinical and cost-effectiveness of physiotherapy with integrated, personalized, multimodal, immersive VR in favor of usual physiotherapy care for patients with CLBP.ClinicalTrials.gov (identifier: NCT05701891).This study is prospectively registered at  Low back pain (LBP) is the principal cause of global disability and accompanied by high health care utilization and societal costs , 2. ChroPrimary care physiotherapy is currently one of the main treatment options for CLBP, mostly consisting of pain education and exercise therapy . UnfortuTo aid the physiotherapist in providing more effective treatment for patients with CLBP, virtual reality (VR) could be of use as an addition to the current primary physiotherapy care . VR is aPrior studies have shown that immersive VR can be successfully used in the treatment of patients with CLBP e.g. , 26). Ho. Ho26]).The primary aim of this study is to assess the effectiveness of physiotherapy with integrated multimodal VR for patients with complex CLBP compared to usual primary physiotherapy care on physical functioning. Secondary aims include the effectiveness on pain intensity, pain related fears, pain self-efficacy, physical activity level, global perceived effect, problems with activities and the cost-effectiveness of physiotherapy with integrated multimodal VR for patients with complex CLBP, compared to usual primary physiotherapy care. This protocol describes the warranted steps to accomplish the aims of this study.www.sealedenvelope.com) will be used for cluster randomization. Cluster randomization was chosen above regular randomization to prevent contamination due to physiotherapists providing both interventions. Patients will be allocated to the intervention or control group that their physiotherapy practice their physiotherapist was randomized in. The flow of participants is shown in the CONSORT flow diagram . A pragmatic, multicenter, two-arm, parallel, superiority, cluster randomized controlled trial (RCT) including 120 patients with CLBP from approximately 20 physiotherapists will be conducted. Physiotherapy practices (with 2–3 participating physiotherapists per practice) will be randomly allocated on a 1:1 ratio to the experimental group that will administer blended care consisting of physiotherapy treatment with integrated, immersive, multimodal, therapeutic VR, or to the control group that will administer usual primary physiotherapy care for patients with CLBP. An online software program .This study was approved by the medical ethical review board  and is registered at n = 20) will be recruited through their practices using convenience sampling through social networks (LinkedIn and Facebook) and physiotherapist networks  and local lower back pain networks). Of each responding physiotherapist practice a maximum of two physiotherapists will be included in the trial, to achieve a heterogenous sample. Physiotherapists are eligible for participation in this study if they: (1) work within 50 km from Enschede or Nijmegen in the Netherlands, (2) have no prior experience using VR as a treatment modality in physiotherapy practice, (3) treat on average at least one new patient with CLBP per month and (4) are willing to cooperate with the study protocol.Physiotherapists (n = 120) will be newly admitted patients that visit the physiotherapist. Patients are considered to be eligible for participation if they meet the following inclusion criteria: (1) CLBP > 3 months as reason to visit the physiotherapist, (2) absence of ‘red flags’ or signs of specific LBP [Participants  notific LBP ) and sevific LBP ), (5) agwww.siilo.com/nl/; frequently used by general practitioners (GPs), physiotherapists and other healthcare professionals) or by calling the researcher. Subsequently, the researcher will send the first online questionnaires to the patient. If the patient decides not to participate, no questionnaires will be sent , and the patient will not be refused treatment by the physiotherapist.Patients visiting a participating physiotherapist practice because of CLBP are screened for study participation by the physiotherapist during the intake. If a patient is eligible, the physiotherapist provides a patient information letter and informed consent form, provides oral information about the study and asks the patient to decide within a few days to participate . In addition, the physiotherapist asks the patient’s permission to send the patient’s name and mail address to the researcher, and register this permission in their regular electronic patient file. If permitted, the physiotherapist provides the researcher the patient’s name and mail address through a fully secured app  the developed intervention and methodology of personalizing the intervention, (2) integration of VR within physiotherapy treatment and (3) practical use of VR headsets.The experimental intervention consists of  physiotherapy with integrated VR.The physiotherapy treatment will consist of 8 to 24 sessions of usual physiotherapy care as described for the control group, complemented with feedback and discussion on the patient’s VR use. Based on the patient’s experience and data on VR use, the physiotherapist can alter the treatment’s intensity, frequency and modality of (VR) treatment. Additionally, physiotherapists are encouraged to use VR for any possible homework exercises.In addition to the usual physiotherapy, physiotherapists in the experimental condition will integrate therapeutic VR in their treatment. Patients will be instructed to use VR on Pico Neo 3  head-mounted displays (HMDs), five times a week for 10 to 30 minutes at home, during the 12-week treatment period. This dosage is based on a review of CLBP trials, which found that 8–12 week interventions with a minimal duration of 20 hours were most beneficial to pain and function  and is cPhysiotherapists and patients select which of the VR modules described below are most suited to the needs and wishes of the patient, using shared-decision making. It is advised to start the first 3 weeks of the intervention with the first two modules (Reducept and SyncVR Relax & Distract) and start with the third module (SyncVR Fit) in the fourth week. Moreover, to emphasize the importance of pain education it is advised to repeat this module in week 8 and 12, as previous research has shown that repetition is crucial in pain education treatment .Reducept : Reducept contains five games, aiming to teach patients with CLBP that pain can be influenced and managed by changing their beliefs about chronic pain. This is done by a combination of pain education and different psychological therapies , mindfulness and visualization). Pain education has shown to be effective in the management of chronic pain, when incorporated within a multimodal therapy . PsycholSyncVR Relax & Distract : SyncVR Relax & Distract contains 50 videos (e.g. swimming with dolphins and city tour of Amsterdam), ten games (e.g. Sudoku and Memory) and five exercises (e.g. breathing and meditation exercises). Relaxation seems to be helpful as an added intervention for patients with CLBP, especially during regular practice , 42. On SyncVR Fit : SyncVR Fit contains 11 movement and sports exercises, including tennis, boxing and archery. Exercise therapy is a common treatment modality in CLBP and is recommended in clinical guidelines , 43. AlsThe following three VR modules will be used:The time schedule of this study is shown in Table All questionnaires used will be in Dutch and have sufficient reliability and validity. Participants will complete questionnaires at baseline (T0), 1 month after the start of the intervention (T1), directly after finishing the intervention (T3), and follow-up after 6 months (T6) and 12 months (T12). All questionnaires will be provided to the patients using an online data management system.Additionally, patients will be asked to report the following demographics at baseline: age, sex, BMI, tobacco use, duration of complaints, comorbidities, occupation, education level, diagnostic and therapeutic procedures in past 6 months, medication use, experience with VR for treatment and entertainment. After the intervention, patients are asked to report other treatments than physiotherapy for their CLBP in the past 12 weeks.Physiotherapists will be asked to report their age, gender, years’ experience as a physiotherapist and specialization before the start of the trial.The following treatment parameters will be reported by all physiotherapists after each physiotherapy treatment: modalities and duration of treatment. Additionally, physiotherapists in the experimental group will report adverse events (AEs) if necessary. These measures will give an insight in the administered physiotherapy treatment.In the experimental group, the following VR parameters will be extracted from the online dashboard: treatment modality and duration  and VAS (before and after use of Reducept).A clinically relevant between-group difference of at least 10 points on the ODI  at 3-monClinicalTrials.gov (identifier: NCT05701891). The two study arms will be compared on baseline using descriptive statistics. Means and standard deviations will be presented for continuous variables (or medians and interquartile ranges in case of a skewed distribution), and frequencies and percentages for categorical variables. We will check for outliers by inspecting histograms and boxplots, the effect of any outliers will be assessed by comparing a 5% trimmed mean to the total mean. Results will be considered statistically significant if p < 0.05 (two-sided testing).All statistical analyses will be done using SPSS version 27  and StataSE version 17 . The statistical analysis plan (SAP) is registered at Effectiveness of the experimental intervention compared to the control intervention will be analyzed on the primary outcome physical functioning. Data will be analyzed using an intention-to-treat, linear mixed-model analysis with maximum likelihood estimation (MLE), comparing both groups on clinical effectiveness at 3 months (primary end-point) and 12 months follow-up, with all follow-up time points included in the analysis. The analysis will be adjusted for major prognostic characteristics that could confound the treatment effects (e.g. pain severity), in addition to important baseline patient (e.g. age) or physiotherapist  characteristics that differ considerably between the two arms. Additionally, per protocol analyses will be carried out as described in the SAP.Similar analyses will be performed for the secondary outcome measures pain intensity, pain related fears, pain self-efficacy, physical activity level and problems with activities. GPE will be analyzed as a dichotomous variable , using logistic multilevel analysis.Besides intervention-related costs, primary and secondary healthcare costs and medication costs will be measured. Also, costs related to presenteeism, absenteeism, unpaid productivity and informal care will be measured. Cost-effectiveness of the experimental intervention compared to the control intervention will be analyzed for the 12-months follow-up period on physical functioning and pain intensity. Cost-utility of the experimental intervention compared to the control intervention will be analyzed for the 12-months follow-up period on quality of life. All patients included in the study will be analyzed, with missing data handled by using Multivariate Imputation by Chained Equations (MICE). Costs and effect differences will be estimated using Seemingly Unrelated Regression (SUR) analyses, in which their possible correlation can be accounted for. The 95% confidence intervals surrounding the cost differences will be estimated using Bias-Corrected and accelerated (BCa) bootstrapping. Subsequently, Incremental Cost-Effectiveness Ratios (ICERs) will be estimated by dividing the differences in costs by the differences in effects. Uncertainty surrounding the incremental cost-effectiveness ratios will be graphically illustrated by plotting BCa-bootstrapped cost-effect pairs on cost-effectiveness planes. Also, cost-effectiveness acceptability curves will be constructed to provide an indication of the probability of physiotherapy with integrated multimodal VR therapy being cost-effective with usual care at different values of willingness to pay .This protocol describes the rationale and design of a large, pragmatic, multicenter cluster randomized controlled trial, aiming to determine the clinical and cost-effectiveness of physiotherapy with integrated, personalized, multimodal, immersive VR compared to regular physiotherapy for patients with CLBP.Opposed to most VR studies, this VR study will be a pragmatic trial in which physiotherapists will integrate VR in their treatment of patients with CLBP, instead of providing VR as standalone treatment. Another strength of this study is the thorough monitoring of patients and their treatment, including five measurement moments for patients with a maximal follow-up of 12 months. Moreover, the VR modules in this intervention are multimodal and will be personalized to the patients’ needs.n = 10) of physiotherapists applying the experimental intervention. Moreover, due to the absence of a sham VR group, we cannot rule out a placebo effect in the experimental group.The preference for a pragmatic trial increases the external validity of the study results. However, this might to some extent compromise the internal validity , due to The results of this study will contribute to the mounting literature on the effect of VR for patients with chronic musculoskeletal pain. Also, the results are interesting for practicing physiotherapists treating patients with CLBP and could aid in the discussion to add eHealth in Dutch physiotherapy care to contest the rising healthcare costs. Last and most important, the complex subgroup of CLBP patients with severe pain and severe disability might receive more effective treatment, when the VR integrated physiotherapy treatment will demonstrate superior effects.


Peri-implantitis is an inflammatory process affecting soft and hard tissues surrounding dental implants, causing progressive marginal bone loss. Peri-implant surgery is the treatment of choice. However, evidence about its impact on patients’ quality of life (QoL) is limited. This study aimed to assess pain and QoL in the first seven post-operative days and measure patient satisfaction at the end of this period. A prospective cohort study was conducted in patients with peri-implantitis. Patients reported pain on a visual analogue scale (VAS) ranging from 0 to 100mm every day during the first week after surgery. They then completed the OHIP-14sp questionnaire. A descriptive and inferential data analysis was used to assess the effect of surgical approach , gender and working status on pain, satisfaction and QoL.P = 0.042), and with the regenerative  or the combined approach . Forty-one patients  completed the daily pain VAS; scores ranged from 0 to 95 mm. Gender, occupation, or type of surgery had no significant effect upon its evolution. The mean total OHIP-14sp score was 16.7 (range = 5 to 33), indicating low to moderate deterioration in perceived oral health. Postoperative OHRQoL was significantly higher in working patients (mean difference (MD): 3.94;  Considering the limitations of this study, postoperative pain was mild to moderate and decreased after the third day. Surgical treatment of peri-implantitis has an impact on QoL, especially when augmentation procedures are involved. This impact is higher in working patients. Key words:Patient-centered outcomes, quality of life, peri-implantitis, peri-implant surgery, dental implants. Over recent decades, the use of dental implants for oral rehabilitation has been proven to be a reliable therapy due to its apparent predictability . HoweverClinical outcomes mainly evaluate inflammation and progression of bone loss and do not consider the patient’s opinion. Knowing the impact of these procedures from the patient’s perspective is of great importance in assessing the overall success of the treatment . The conA prospective cohort study was conducted in consecutive patients receiving surgical treatment for peri-implantitis in the course of the Master’s Degree Program in Oral Surgery and Implantology at the University of Barcelona . The protocol was approved by the Ethics Committee (CEIm) of the University of Barcelona Dental Hospital (2014/20) and the study was conducted in accordance with the Declaration of Helsinki on human studies. The STROBE Statement guidelines for cross-sectional studies were applied in the study design and data reporting . Individ- Case definition of peri-implantitisPreoperative analysis included complete medical histories and clinical examination, and examination of periapical radiographs taken with a positioner using the long-cone paralleling technique. Patients with peri-implantitis according to the definition of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions  were inc- Patients with implants with bleeding on probing and/or suppuration; increased probing pocket depths and progressive bone loss.- In cases without previous records, implants with bleeding or suppuration on gentle probing, PPD 6mm and bone level 3mm apical to the most coronal part of the rough surface of the implant.If a patient required multiple surgeries, only the first one was recorded.The exclusion criteria were general contraindications to implant surgery, radiotherapy in the head and neck area, uncontrolled diabetes, current pregnancy or lactation, alcohol abuse and previous history of peri-implant surgical treatment. Patients were excluded if they did not complete the postoperative pain visual analog scales (VAS) or the OHRQoL questionnaire.- Management of peri-implantitiset al.  a reet al. .Written postoperative instructions and drug prescriptions were given to the patients after the surgical procedure. All patients were prescribed 750 mg of amoxicillin every 8 hours for 7 days and 600 mg of ibuprofen every 8 hours for 5 days. If needed, patients were instructed to take 1g paracetamol. They were also instructed to rinse twice daily for 2 minutes with 0.12% chlorhexidine digluconate with 0.05% cetylpyridinium chloride, for two weeks.- Data samplingA trained researcher (I.P-B.) collected all the data. This included age, gender, educational level , occupation, location (maxilla or mandible), position , number of implants treated, peri-implant probing depth without prosthesis assessed at 6 sites per implant on gentle probing  and surgical approach .After surgery, the patients were asked to fill in a pain questionnaire every 24h during the first week. Pain was measured on a 100 mm visual analogue scale (VAS), with 0 mm representing “no pain” and 100 mm “worst pain imaginable”. The participants were also asked to report the daily number of rescue Tablets they took.Seven days after the peri-implant surgical treatment, all the patients completed the Spanish version of the Oral Health Impact Profile questionnaire OHIP-14sp) (sp (14). - Statistical analysisThe statistical analysis was carried out with Stata14 .The postoperative VAS score was the primary outcome variable, while OHIP-14sp and PSPSQ scores were considered the secondary outcome variables. Categorical outcomes were presented as absolute and relative frequencies. The groups were compared through bivariate analysis with Chi-square tests, or Fisher’s exact tests when Chi-square test assumptions were not fulfilled. Normality of scale variables was explored using the Shapiro-Wilk test and visual analysis of the P-P plot and box plot.Where normality was rejected, the interquartile range (IQR) and median were calculated. Where the distribution was compatible with normality, the mean and standard deviation (SD) were used. Differences between groups of scale variables were explored using parametric tests ), or nonparametric tests .To analyze the influence of gender, educational level, working status, surgical approach, and number of implants on pain evolution, a repeated measures mixed model for each categorical covariate was built. Fulfillment of the assumptions was checked by means of the graphical distribution of the residuals.P < 0.05, using Bonferroni’s correction for multiplicity of contrasts. To determine the power for surgical approach and OHRQoL, post-hoc ANOVA using Cohen’s ƒ2 test was performed.The reliability of each questionnaire was assessed with the Cronbach α coefficient. The level of significance was set at Of 45 patients treated with peri-implantitis surgery, 41 (81.1%) completed the questionnaire. The mean age of the participants was 61.5 years ± 10.5. The majority of the patients included were women (61.0%). Mean peri-implant probing depth was 4.9 mm ± 2.0. P < 0.001). Daily VAS scores with a 95% confidence interval (CI) are shown in Fig. P < 0.001; day 2 vs. days 5 to 7: P < 0.001; day 3 vs. 5 to 7: P ≤ 0.002; day 4 vs. day 6 and 7: P < 0.001; and day 5 vs. day 7: P < 0.001). The VAS pain scores did not differ between any of the grouping levels (P ≥ 0.05) (P ≥ 0.05).VAS pain scores decreased significantly over time   and the The percentage of patients who took analgesics on each day and the mean number of days of analgesic intake are shown in P = 0.041 for 2-3 implants and P = 0.014 for ≥4 implants).All the groups soon discontinued the use of paracetamol. Patients who had a single implant treated took significantly more analgesics on days 2 and 3 than patients who required treatment to several implants (P = 0.042).The impact of peri-implant surgical therapy on OHIP-14sp is reported in P = 0.044; combined vs. resective MD: 5.41 points; 95%CI: 0.48 to 10.35; P = 0.027)  .Regarding PSPSQ, 78.0% of patients were satisfied with the treatment and 87.8% would recommend it. However, 36.6% would not repeat it and only 51.2% felt that their problem had been solved. Almost a third of the patients reported the maximal level of satisfaction  16)..16).As with any other oral surgical procedure, the treatment of peri-implantitis had an impact on the patient’s quality of life. The participants reported moderate pain during the first 3 days, which decreased progressively from the fourth day. The mean total OHIP-14sp score was 16.7, and the subjects frequently reported an impact on their quality of life in the physical pain and physical disability domains. Approximately 80% of the patients were satisfied with the treatment but one third of the participants would not repeat it.To the best of authors’ knowledge, this is the first study to have evaluated changes in the quality of life during the first postoperative week in patients who have undergone peri-implant surgeries. The present study adds new and relevant data that will help clinicians in their choice of treatment. Patient-centered outcomes (OHRQoL and PSPSQ) are of the outmost importance and should be considered and discussed with patients before performing any treatment ,16. The The present outcomes suggest that the effect on the patient’s quality of life after surgical treatment of peri-implantitis is similar to other oral surgical procedures ,19. RepoWorking participants reported significantly higher OHIP-14sp scores although sick leave was uncommon. The pain and disability could well have had an impact on the patient’s working life, which might explain the higher impact on their OHRQoL in comparison with participants who were not in employment. Likewise, the surgical approach also seems to be a relevant variable. Augmentation techniques (regenerative or combined approaches) had a higher impact on OHRQoL probably because of the more extensive flap manipulation and periosteal releasing incisions, which might cause additional pain and swelling.Understanding the impact of peri-implant disease management on the OHRQoL is essential. Not only is information on patient-centered outcomes lacking, but at least 75% of patients seem to be unaware of the existence of peri-implant pathology ,16, whilEven though 80% of the patients were satisfied with the surgical treatment, more than one third of the participants (36.6%) would not repeat the treatment. This is probably related with the moderate pain experienced in the first 72 hours and with the impact on their quality of life.The success rates of peri-implantitis treatment depend on multiple factors, but the progression of bone loss can be stopped or at least slowed down in the majority of the cases . Early tOne limitation of this study is related to the limited experience of the clinicians who performed the peri-implant treatments, which might increase the impact on the OHRQoL, since more experienced surgeons are faster and are likely to achieve better outcomes. On the other hand, the fact that several clinicians were involved in the surgical procedures increases the external validity of these results. It is also important to stress that these results are limited to the first postoperative week and those variables like flap extension, implant position and the severity of the disease were not assessed. Further research should focus on the medium- and long-term impact of these treatments.Surgical treatment of peri-implantitis has an impact on the patient’s OHRQoL, especially when the patient is in work or when regenerative or combined approaches are employed. Postoperative pain was mild to moderate in the first 72 hours, showing a steady decrease from the fourth postoperative day. Patient satisfaction was high despite one third of the patients’ not wishing to repeat the procedure.


As part of the STAR Programme, a comprehensive study exploring long-term pain after surgery, we investigated how pain and function, health-related quality of life (HRQL), and healthcare resource use evolved over 5 years after total knee replacement (TKR) for those with and without chronic pain 1 year after their primary surgery.We used data from the Clinical Outcomes in Arthroplasty Study prospective cohort study, which followed patients undergoing TKR from two English hospitals for 5 years. Chronic pain was defined using the Oxford Knee Score Pain Subscale (OKS-PS) where participants reporting a score of 14 or lower were classified as having chronic pain 1-year postsurgery. Pain and function were measured with the OKS, HRQL using the EuroQoL-5 Dimension, resource use from yearly questionnaires, and costs estimated from a healthcare system perspective. We analysed the changes in OKS-PS, HRQL and resource use over a 5-year follow-up period. Multiple imputation accounted for missing data.Chronic pain was reported in 70/552 operated knees (12.7%) 1 year after surgery. The chronic pain group had worse pain, function and HRQL presurgery and postsurgery than the non-chronic pain group. Those without chronic pain markedly improved right after surgery, then plateaued. Those with chronic pain improved slowly but steadily. Participants with chronic pain reported greater healthcare resource use and costs than those without, especially 1 year after surgery, and mostly from hospital readmissions. 64.7% of those in chronic pain recovered during the following 4 years, while 30.9% fluctuated in and out of chronic pain.Although TKR is often highly beneficial, some patients experienced chronic pain postsurgery. Although many fluctuated in their pain levels and most recovered over time, identifying people most likely to have chronic pain and supporting their recovery would benefit patients and healthcare systems. A strength of the study is that participant-level data were collected over 5 years after total knee replacement enabling a detailed analysis of changes over time.The study cohort offered data on patient-reported outcome measures, allowing for a classification of participants according to their chronic pain status following surgery, and linked healthcare resource use to include in the analysis.This study followed pain trajectories of participants with postsurgical chronic pain which has not previously been explored.An important limitation was that many follow-up questionnaires were not returned, which generated an important level of missing data, addressed using standard methods of multiple imputation.The longitudinal study questionnaires did not ask participants about informal care, productivity losses or their use of privately funded healthcare other than physiotherapists, which may play an important role in associated costs.Total knee replacement (TKR) provides pain relief and increases function for many people with advanced-stage knee osteoarthritis, which improves health-related quality of life (HRQL). However, a distinct, important group of people report long-term (chronic) pain after their TKR.Although pain trajectories after TKR have previously been explored,Assessing clinical and cost-effectiveness is a critical step in informing decision-making about the wider implementation of new interventions. For cost-effectiveness studies of potential new interventions for CP following surgery to be carried out, our understanding of the progression of CP must be accompanied by an assessment of HRQL and costs. HRQL is affected by a number of factors including the severity of pain and its consequences and is expected to vary as people’s pain improves, worsens or fluctuates. Changes in pain are also likely to impact healthcare use, such as follow-up hospital visits, general practitioner (GP) appointments, or prescriptions of analgesia. Healthcare resource use and costs after a TKR have been previously describedThe Clinical Outcomes in Arthroplasty Study (COASt), a prospective cohort study, tested outcome prediction models’ performanceCOASt recruited patients receiving a joint replacement from the Nuffield Orthopaedic Centre in Oxford from 2010 and the Southampton General Hospital from 2011 (both in England). Patients were invited to participate after they were placed on the waiting list for a primary or revision knee replacement regardless of age, gender, body mass index (BMI) or underlying cause for the surgery. Baseline information was collected in preoperative questionnaires that covered participant demographics such as the Index of Multiple Deprivation  and patient-reported outcome measures (PROMs): HRQL  and pain and function . COASt participants were followed up with yearly postal questionnaires for 5 years postsurgery.We included COASt participants who underwent a primary TKR, returned their questionnaires 1 year after surgery and completed the OKS Pain Subscale (OKS-PS) in that questionnaire for the resource use analysis. We excluded bilateral surgeries to be able to track levels of pain of a single operated knee. We did not have information about which patients had a revision surgery, which is highly unlikely during the first years after primary, or whether they had a contralateral operation. For the pain, function and HRQL analysis we also included participants who did not complete their OKS-PS at 1 year, in which cases missing data were imputed. Patients listed for hip or knee replacement surgeries in the two participating centres (Southampton and Oxford) were potentially eligible for inclusion. Once identified, potential participants were sent a recruitment pack, consisting of a patient information sheet, a sample consent form and a recruitment letter. They were later contacted by telephone by a member of the COASt team around 2 weeks after the pack was sent to discuss study details and answer any question they might have had. The COASt team member then took verbal consent if patients were satisfied and willing to participate in the study.9Patient and public involvement (PPI) members were actively involved in the design and recruitment of the STAR programme. PPI members participated in over 20 meetings of the STAR Patient Forum to discuss and improve the participant experience. They gave feedback and recommended changes for both recruitment and study materials for the STAR trial, which was further informed by the results of this study. Findings were disseminated to study participants via regular programme bulletins and through STAR Patient Forum meetings.Pain and functional ability were measured with the OKS, a patient-reported questionnaire consisting of 12 items assessing a patient’s perspective of their joint pain and function after a TKR.The OKS-PS was used to identify those in CP, following work by some of our co-authors. The OKS-PS includes the 7 OKS questions relating to pain and is summarised by a score of 0–28.4HRQL was measured using the EQ-5D-3L questionnaire, which examines five dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. This instrument was completed at baseline (just before surgery) and annually after the TKR for 5 years. A health utility estimate, anchored at 0 representing death and with 1 representing full health, was calculated by applying a social preference tariff collected from a sample of the UK general population.12Healthcare resource use was measured using participants’ answers to questions about their visits to GPs, nurses, physiotherapists, alternative practitioners and admissions to hospitals, because of their operated knee. These questions were included in the baseline and all follow-up questionnaires and covered the preceding 12 months.The value of healthcare resources was estimated from the National Health Service (NHS) perspective by applying mean unit costs sourced from the Personal Social Services Research Unit14Lost to follow-up during the 5 years led to increasing amounts of missing data. Missing data and attrition are an important concern for longitudinal studies. It has been argued that the imputation of missing covariates data in medical research is always better than the complete case.Therefore, multiple imputation assuming data missing at random was implemented to reduce the potential biases arising from missing data. Fifty imputed datasets were generated, with missing OKS-PS and EQ-5D values replaced by imputed ones.18We characterised HRQL and pain outcomes, resource use, and costs by CP group  over 5 years by reporting the mean and SD of the imputed OKS, OKS-PS, health utility, number of healthcare visits and healthcare costs from presurgery to 5 years postsurgery. In addition, for OKS-PS and health utility we reported 95% confidence intervals. We considered presurgery as well as postsurgery to investigate whether those with CP postsurgery report distinct differences even prior to surgery.To investigate the trajectory of CP, we tracked CP-group participants’ movement in and out of CP and report the percentage that remained in CP for the entire period, recovered from CP at any point, and fluctuated between CP and non-CP over the 5 years. A participant’s CP group status at each time point was determined by their observed OKS-PS, if available, or the mean across the 50 imputed scores, if missing. Transitions in and out of CP are illustrated in a Sankey diagram.To investigate whether leaving the CP group after year 1 led to changes in HRQL or costs, we compared observed health utility and healthcare costs of CP-group participants who recovered from CP by year 2 after surgery and those who did not.All analyses were conducted in R V.4.0.335Of the 1025 knee procedures enrolled in COASt, all 580 corresponding to a TKR returned their year-1 follow-up questionnaire. We excluded 28 who did not report their OKS-PS in that questionnaire, giving a final sample of 552. Seventy  were classified as in CP 1 year after surgery using the OKS-PS. We refer to those classified as in CP 1 year after TKR as the CP group, and those not in CP 1 year after TKR as the non-CP group.Observed and imputed data showed similar mean health utility and OKS-PS scores . Observe10.1136/bmjopen-2021-058044.supp1Supplementary dataThe CP and non-CP groups had different mean health utility estimate scores before surgery  althoughThere were similar patterns in pain progression, measured with the OKS-PS . The nonThe groups’ average annual number of visits to physiotherapists, hospital doctors, nurses and alternative practitioners differed by healthcare specialist, but showed similar patterns. The CP and non-CP groups made similar numbers of visits before surgery; numbers surged for both groups during the 12 months after surgery, especially for the CP group. Visits then progressively decreased over the rest of the follow-up period for both groups. Although most physiotherapy visits were to NHS practitioners, during the first year postsurgery the CP group reported an average of four visits to NHS physiotherapists and three visits to private physiotherapists, whereas the non-CP group respectively made 2.2 and 0.6 visits. The groups’ number of visits to Accident and Emergency, readmissions to the same hospital, and admission to any other hospital all showed similar patterns over time as the visits to non-GP healthcare professionals.Participants in the two groups had similar mean healthcare costs in the year before surgery: £430 (SD=611.41) for the CP group and £322 (SD=337.22) for the non-CP group. Mean health utility remained stable for those who remained in the same CP group between years 1 and 2, while those who moved into CP saw their health utility drop and those who recovered from it reported a clear improvement .The groups’ healthcare costs followed similar patterns to their health utility scores . ParticiOur analysis of data from COASt found that, on average, TKR led to large HRQL improvements, with health utility scores improving from 0.447 before surgery to 0.742, 1 year after surgery. This improvement is consistent with what has been reported in previous studies,1–3 5Our characterisation of pain and function, HRQL, and healthcare resource use and costs by participants with and without CP 1 year after surgery suggests that these groups are distinct. However, CIs are wide and overlap. Study participants in the non-CP group reported rapid, significant improvements in OKS-PS, OKS and EQ-5D over the 5 years after surgery, whereas those with CP improved much less and much more slowly. It’s not surprising that the pain, composite pain and function, and HRQL measures changed in similar ways, given their close association.Two-thirds (64.7%) of participants with CP recovered and were no longer in CP within 5 years after surgery. This result suggests that CP after TKR is not a permanent condition and can improve with time as patients access routine care. There can be many reasons for these changes. They could be linked to individual characteristics, day-to-day life, or the severity of the original condition. Qualitative work from the STAR (Support and Treatment After Replacement) programme suggests that acceptance and self-management could potentially play a role, although this is an area that needs more research.39 40Most of those who recovered from CP did so during the second year after surgery. One possible explanation for the prolonged recovery period from postsurgical pain may be in relation to the different pain mechanisms which are involved in OA.46–49et alOnly 4.4% of participants reported OKS-PS scores that indicated CP for all 5 years after surgery. Brander One-third (30.9%) of participants reported fluctuating OPS-PS scores that classified them as experiencing CP at only certain points during the study period. Relief from CP may not always be permanent, which is consistent with the variability in temporal fluctuation in knee pain seen without surgical intervention.Participants in CP after the first year after surgery who recovered by the second year improved their health utility more than those who stayed in CP, but not as much as those who were not in CP in either year. Improved OKS-PS is a sign of less pain. As it is likely associated with improved mobility, self-care and conduct of usual activities, it would be expected to lead to improved EQ-5D scores. However, participants switching CP groups also reported changes in use of healthcare resources that separated them from the CP group and brought them closer, although not directly in line with, participants without CP. These findings suggest progressive improvement as people come out of CP. The OKS-PS cut-off used to identify CP may therefore be sensitive enough to identify distinct groups as they transition between CP categories.Our results suggest that under current clinical practice, many patients leave CP over time by gradually improving. Identifying these patients early will allow clinicians to provide them with tailored support to make that transition as quickly as possible. Better understanding which patients remain in CP or only recover after many years of struggling with pain will also help clinicians to design interventions to improve and manage these patients’ pain, allow them to continue with their lives with the least interference possible.This study has several potential limitations. As our analyses used data collected from patients recruited from two hospitals in Southampton and Oxford, the findings are not necessarily generalisable to the rest of the country. However, the participants’ health gains after TKR agreed with those reported by the NHS PROMs programme,Our categorisation of CP was made using an OKS-PS cut-off score. As pain is a complex construct, it might not be appropriate to dichotomise it via a threshold on an instrument designed to measure improvement after knee replacement, rather than capturing the diverse dimensions of the pain experience. However, the use of this cut-off point to identify people with and without CP effectively distinguished between groups with significantly different health outcomes (including HRQL), resource use and healthcare costs,The questionnaires used in COASt resulted in many study limitations, only some of which could be mitigated against. Many follow-up questionnaires were not returned, which generated an important level of missing data. It is difficult to know the direction of the impact this may have had as participants may not return questionnaires for multiple reasons, including both being very dissatisfied with their surgery or doing so well they could not be bothered to respond. We addressed this issue by applying multiple imputation to reduce bias and improve our study’s power.54The questionnaires did not allow us to identify specific interventions received by participants after TKR, only unspecified hospital readmissions. We were, therefore, unable to identify whether the improvements observed were due to any particular interventions or treatments. Moreover, lacking specific intervention details was a limitation to estimate costs to the NHS, but we addressed this by using average unit costs weighted by their relative use in the NHS.14As the resource-use questionnaires asked patients to report events that had occurred over the previous 12 months, they were potentially subject to recall bias. However, we are confident that most hospitalisations are sufficiently significant events for participants to have recalled them all. However, this may not be the case for less significant events such as a routine GP visit. Due to the potential bias from the self-reported resource use and the influence from factors not available for this study, the costs estimation should be used with caution and considered a broad estimate.The questionnaires did not ask participants about informal care, productivity losses, or their use of privately funded healthcare other than physiotherapists. Although these issues are relevant for TKR patients, excluding this information was consistent with the perspective adopted for this analysis, that is, that of the healthcare payer (NHS).This study’s main strength is the rich longitudinal dataset used. Unlike the national PROMs programme, which only collects PROMs before and 6 months after surgery, COASt collected data for 5 years after TKR. It also offered data on both PROMs and healthcare resource use, allowing us to explore the patterns in both.Further research building on our findings is warranted. Identifying how best to assess presurgical and postsurgical factors may help to provide more detailed understanding of variation in and potential predictors of CP and the likelihood and speed of recovery. We believe that including measures such as neuropathic pain, catastrophising, sleep disturbance, anxiety, depression, pain medication intake, self-prescription and physical activity, among others, would help build a comprehensive, informative picture. In the meantime, clinicians can reassure patients that, though many fluctuate in their levels of pain, CP after TKR is generally not permanent and that improvement over the 5 year after their primary is likely for many, if not most.We identified a significant, rapid improvement in HRQL for people undergoing a TKR. This overall trend, however, appears to hide the slow and gradual improvement experienced by people with CP 1 year after their primary. They differed from those not in CP in terms of their progression of pain and function, HRQL, healthcare resource use and costs. Our study suggests that the majority of people with CP after the first year eventually recovered by the fifth year after TKR, reducing their need for healthcare. Further research is needed to understand the reasons for this difference in progression as well as who is most likely to develop CP after TKR and how best to support patients in their long-term recovery, benefiting patients, their families and healthcare systems.


Neck pain and functional impairment are common complications of traffic accidents (TAs); however, the effects of manual therapy on these symptoms have rarely been studied in the literature. Thus, this randomized controlled trial aims to assess the effectiveness and safety of non-resistance manual therapy (NRT)—a treatment combining mobilization and pressure release techniques—on acute neck pain caused by TA.This study will use a two-armed, parallel, assessor-blinded randomized controlled trial design and will be conducted in the Daejeon Jaseng Hospital of Korean Medicine in South Korea. One hundred twenty patients will be recruited and randomized into an integrative Korean medicine treatment (IMKT) + NRT group and IMKT group in a 1:1 ratio. The primary outcome is a change in the numeric rating scale for neck pain immediately after treatment on hospital day 5 compared to those at baseline. The secondary outcomes are numeric rating scale for radiating arm pain, visual analogue scale for neck pain and radiating arm pain, cervical active range of motion, neck disability index, Patient Global Impression of Change, Short Form-12 Health Survey, and Posttraumatic Stress Disorder Checklist for DSM-5.The findings of this study on the effectiveness and safety of NRT will be helpful for patients with TA-induced neck pain in clinical practice and will provide evidence for developing relevant healthcare-related policies.This protocol has been registered at Clinicaltrials.gov (NCT04660175). Some clinical guidelines recommend active exercise, passive joint mobilization, heat, ice and massage, electrotherapy, simple analgesics, and nonsteroidal antiinflammatory drugs for treating acute (≥12 weeks of onset) whiplash associated disorders.Traffic accidents (TAs) are a common cause of neck pain, and cervical injury and relevant heterogeneous disorders caused by acceleration and deceleration of vehicles are collectively referred to as the whiplash syndrome. In Korean traditional medicine, neck pain is generally treated by acupuncture, electroacupuncture, herbal medicine, Chuna manual therapy, pharmacopuncture, bee-venom pharmacopuncture, cupping therapy, and Doin therapy.In Korea, many patients suffering from whiplash associated disorder seek Korean medicine treatment, although it is not covered by auto insurances. According to auto insurance medical cost statistics, Korean traditional medicine accounts for 48% of all medical costs. Cervical nonresistance manual therapy (NRT) is a type of Chuna therapy comprising joint mobilization and pressure release techniques. Mobilization techniques are used in osteopathy and chiropractic therapies. Manual therapy using a pressure release technique is also performed in various countries worldwide.–11Chuna manual therapy is an advanced form of traditional Korean manual therapy that incorporates various forms of manual therapies used in other countries.,12–14 However, well-designed randomized controlled trials (RCTs) on these manual therapies are lacking. This parallel-group RCT aims to assess the effectiveness and safety of NRT on TA-induced neck pain. The hypothesis is that additional NRT with integrative Korean medicine treatment (IKMT) is superior to IKMT alone.Many studies have suggested that compared to treatments for acute whiplash injury that involve joint fixation, treatments that do not involve joint fixation, such as movement within range of motion (ROM) and mobilization, are more effective in the long term.22.1This is a protocol for a two-arm parallel RCT that will be conducted in the Daejeon Jaseng Hospital of Korean Medicine. This protocol was approved by the Institutional Review Board at the Daejeon Jaseng Hospital of Korean Medicine prior to patient recruitment (JASENG 2020-10-007). Further, the protocol has been registered at Clinicaltrials.gov (NCT04660175), and the progress of the study will continue to be updated. One hundred twenty inpatients of Daejeon Jaseng Hospital of Korean Medicine with TA-induced acute neck pain who will meet the inclusion criteria and sign an informed consent form will be enrolled. The patients will be recruited within the hospital. Once enrolled, the patients will complete seven visits from hospital day 1 and complete six surveys during their hospital stay and one survey after discharge.2.22.2.11.Age 19 to 70 years2.TA-induced acute neck pain that developed in the last 7 days3.Hospitalization due to acute neck pain4.Numeric rating scale (NRS) of neck pain ≥55.Voluntary signing of a written informed consent form to participate in the clinical trial2.2.21.Diagnosis of a severe disease that could cause acute neck pain 2.Progressive neurological defect or severe neurological symptoms3.Pain caused by soft tissue diseases and not the spine 4.Other chronic diseases that may hinder the interpretation of the effects or outcomes of treatment 5.Current use of steroids, immunesuppressants, antipsychotic drugs, or other drugs that may affect the study outcomes6.Pregnancy, plan to conceive, or breastfeeding7.Cervical surgery or procedure in the past 3 weeks8.Severe mental disorder9.Less than 1 month since participation in another clinical trial, plan to participate in a study within 12 weeks of enrolment, or plan to participate in another clinical trial during the follow-up period10.Failure to sign the consent form to participate in the study11.Other reasons that hinder participation in the clinical trial as determined by the investigators2.3The participants will be randomized into the experimental group and control group. The control group will receive acupuncture, Chuna therapy, pharmacopuncture therapy, and herbal medicine treatments during their hospital stay, while the experimental group will receive NRT in addition to IKMT. All interventions will be performed by Korean medicine doctors with at least 1 year of clinical experience who have been trained for the trial and are familiar with the study procedure.2.3.1For the experimental group, four sessions of NRT will be administered from hospital day 2 to 5, and IKMT will be administered daily. Each session of NRT will last for about 10 minutes.During the NRT, the patient will be seated, and the therapist will apply pressure to the cervical treatment point while firmly supporting the patient's head and progressively extending the neck to move the joint. The therapist will apply pressure to the posterior neck with the thumb and other fingers while supporting the occipital region with the dorsum of the hand.st and 2nd metacarpal bone; and place the other hand on the patient's forehead. Then, light flexion and extension will be repeated within the ROM of the cervical spine without pain. The weight of the patient's head will add weight to the hand supporting the head and, thus, will transfer pressure to the thumb and index finger, and compression and relaxation will be repeated based on the transferred pressure. During the treatment, the therapist will comfort the patient by assuring them that the treatment does not cause pain so that the patient can relax the neck muscles. Once the targeted area is adequately flexed and extended over a sufficient period of time, the pressure points will be moved to the central and lower neck to repeat the procedure. The range of cervical extension increases at the lower neck area .With the patient seated on a chair, the therapist will place the thumb and index finger on the areas around the articular pillar in the upper cervical region with tense muscles or on the acupoints GB20, BL10, GB21, or SI15; support the back of the patient's head with the 12.3.2This group will receive acupuncture, Chuna therapy, pharmacopuncture therapy, and herbal medicine treatments during their hospital stay.2.3.3The participants will not be prevented from seeking additional treatment for pain during the study period. They will be instructed to notify the investigator immediately they develop an adverse event or receive additional treatment, which will subsequently be recorded in detail.2.41.In the case of participant who have been found to have a disease that could affect the decision of the study result that was not discovered at baseline assessment.2.During the clinical study period, when the participant or participant's legal representative requests to discontinue the study, or the participant withdraws consent.3.Confirmation during treatment.4.Existence of a problem in performing medical or oriental medical treatment for neck pain.5.In case the continuation of participation is not appropriate due to the judgment of the researcher.2.52.5.12.5.1.1It is a measure of the patient's subjective neck pain. Patients are instructed to choose a number from 0 to 10 that best represents the degree of their current pain .2.5.22.5.2.1,16It is a measure of patients’ subjective radiating arm pain. Patients are instructed to choose a number from 0 to 10 that best represents the level of their current discomfort .2.5.2.2,17The VAS is a 100-mm line with one end indicating no pain and the other end indicating the worst imaginable pain, and patients are instructed to choose a point on the line that indicates their level of pain, which represents their neck pain and radiating arm pain in the past week.2.5.2.3The maximum active ROM for the cervical spine  without pain are measured.2.5.2.4,18Functional status will be assessed using the NDI. The NDI was developed as an index for the severity of neck disability. The NDI comprises 10 items, and each item is scored on a scale from 0 to 5. The total possible score is 50. The total score is divided by the number of answered items to compute the average score.2.5.2.5The PGIC allows patients to subjectively assess the level of their improvement on a seven-point scale as follows: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.2.5.2.6The SF-12 is a questionnaire for health-related quality of life (HRQoL), and it comprises 12 items in 8 domains . The questionnaire is completed in about 5 minutes, and a higher score indicates a better HRQoL. The SF-12 is used to assess functional health and well-being of patients and healthy individuals. The Korean version of the SF-12 was validated by Kim et al based on 1000 Korean people for assessing HRQoL.2.5.2.7The PCL is one of the most widely used self-reported scales for post-traumatic stress disorder. For patients involved in a TA, it is used to assess the level of post-traumatic stress disorder caused by trauma from TAs. We will use the Korean version of the PCL that has been adapted and validated by Kim et al.2.5.3The types and doses of drugs taken during the study period (drugs prescribed for current illness or rescue drugs) will be examined based on the questionnaires. The patients will also be instructed to record the frequency of other treatments, such as physiotherapy and injections.2.5.4AEs refer to undesirable and unintended signs, symptoms, or diseases that occur post-procedurally during the clinical trial , and they do not have to be causatively associated with the procedure. The investigators will assess the causality between the treatment modality and each AE based on the 6-level World Health Organization-Uppsala monitoring center causality assessment system . In addition, all AEs will be categorized into three severity levels based on the Spilker classification system (Mild (1): does not significantly impair daily activities (function) nor require additional medical intervention; Moderate (2): significantly impairs daily activities (function) and may require additional medical intervention but will resolve; Severe (3): severe AE that requires intense medical intervention and leaves sequela).2.6At the screening visit, the participants will be enrolled after signing a written consent form, and those who qualify per the inclusion/exclusion criteria will proceed with the trial. The detailed timeline is shown in Table 2.7α) was set at 0.05 (two-tailed), type 2 error (β) at 0.2, and power at 90% to calculate the sample size. The sample size was determined with reference to a previous pilot study. The Cohens’ d was 0.63, and the correlation between the baseline and endpoint measurements was assumed to be 0.5. A total of 41 participants were needed per group. Based on a 30% potential withdrawal rate, the target number of participants was set to 60 for each group.The null hypothesis of this study is that there will be no differences in the improvement of acute neck pain between the experimental group and control group after the additional use of NRT by the experimental group, and the null hypothesis will be tested using analysis of covariance as the primary analysis. The significance level  will be provided to the investigators, including the assessor and physicians, and they will be trained for the assessments and data entry based on the SOP. Only the investigator who is responsible for data management can access the data recorded on the case report form. The investigators will be in touch with the patients for 12 weeks for the follow-up assessments, and the patients will be allowed to ask study-related questions at any time during the study period by contacting the investigator through the investigator's contact information provided prior to the beginning of the study. Patients who have to discontinue the study will be followed up upon providing consent for follow-up.2.11In this study, both the intention-to-treat and per-protocol analyses will be performed, with intention-to-treat as the primary analysis. In the per-protocol analysis, participants who receive at least three sessions of treatment will be analyzed separately. The NRT + IKMT group and IKMT group will be compared, and the aim is to evaluate the superiority of NRT + IKMT.Missing values will be processed through a mixed model for repeated measures in the primary analysis, and multiple imputations and the last observation carried forward will be performed for sensitivity analysis. For the Kaplan-Meier curve and log-rank test, the patients who drop out will be right censored, and regarding intermittent censoring, we will assume that no event occurred during the specified time period.t test or Wilcoxon-rank sum test depending on the distribution pattern. Categorical variables will be presented as frequency (%) and will be analyzed using chi-square test or Fisher's exact test.The sociodemographic characteristics of the participants and treatment expectancy will be evaluated by group. Continuous variables will be presented as mean (standard deviation) or median (quartile), and the two groups will be compared using the Student The endpoints of this clinical trial are the changes in the continuous outcomes  at each time point from the baseline. A linear mixed model will be used as the primary analysis, and a random intercept model, which includes subject the random effects. Fixed effects will include baseline outcomes and clinically important covariant factors that are statistically significantly differ between groups at baseline as the covariates. In addition, time, group allocation, and the time and group interaction will be included in the model to examine the differences in the amount of change over time between the groups. For sensitivity analysis, we will perform analysis of covariance on the multiple imputations and last observation carried forward sets with the same covariates as those in the primary analysis and the group set as the fixed factor.To compare the number of changes for each outcome within the study period (during treatment and the entire study period) in both groups, we will calculate the areas under the curve at each time point following randomization. The time from randomization to the point at which NRS reduces by more than half of the score will be compared using the Kaplan-Meier survival analysis, and the curves will be compared using a log-rank test. Additionally, we will use the Cox Proportional Hazard Model to compare hazard ratios. We will perform subgroup analyses and compare the degree of pain improvement between the NRT + IKMT group and the IKMT group.P < .05.The significance level will be set at .05 for all analyses. All statistical analyses will be performed using the SAS 9.4  or R version 4.1.1  software, with the statistical significance set at 2.12We will monitor the data to ensure participants’ safety and the integrity of the study data. During monitoring, case records and evidence documents will be compared, and participants’ safety data will be reviewed. The initial monitoring will be performed during participant screening and enrolment, and at least two rounds of monitoring will be performed during the study period. The number of monitoring rounds can be adjusted upon discussion among the investigators. Interim analysis will not be performed during this clinical trial.2.13The study protocol, case report form, and informed consent form will be submitted to the Institutional Review Board, and the study will be initiated once it is approved. An amendment of the documents will be approved by the Institutional Review Board in advance, and the documents will be continuously updated. All participating investigators will undergo clinical trials and relevant training and will familiarize themselves with the protocol and SOP. Prior to beginning the trial, the investigators will provide the participants with an information sheet outlining the purpose of the study, timeline, and information to be collected to obtain their informed consent, and a copy of the information sheet will be provided to the participants.2.14Before the start of the study, the researcher will provide the patients with appropriate information about the study for a sufficient time and fills out the study consent form. The signed consent form of the researcher and the participant is kept by the researcher and a copy is provided to each participant.2.15All personal data of the participants will be managed rigorously per the Personal Information Protection Act, and all data collected from the consenting participants will be processed anonymously. If the study data are provided to any third organization for professional data analysis, the data will be de-identified and given arbitrary identification codes. All information regarding this clinical trial, including participants’ personal information, will be retained for 3 years following the completion of the study, after which they will be discarded in accordance with the established protocol.2.16Participants can contact the sub-investigator at any time regarding a study-related injury or for other medical purposes using the contact information provided in advance. If a participant develops an injury directly due to the study procedure, we will provide the best medical interventions and compensation per the designated trial-related insurance.3,24 Technically, NRT is a technique that combines joint mobilization and pressure release techniques. Mobilization is effective for the whiplash syndrome, which is characterized by impaired cervical flexor and extensor functions due to neck injury and pain caused by acceleration and deceleration of a vehicle. Mealy et al reported that patients with a whiplash injury who underwent repetitive and passive movements within tolerable ranges had better outcomes than had their counterparts who simply rested or had cervical braces for the first 2 weeks. These authors utilized small movements within limited amplitudes, with smaller amplitudes for spasms and larger amplitudes for stiffness. A pressure release technique is a common technique used in manual therapy, and Pecos-Martin et al improved the pressure pain threshold and strength of the levator scapulae by applying 60 to 90 seconds of pressure on nuchal muscles.NRT can enhance impaired functions and alleviate pain in patients with acute neck pain caused by a TA by helping them overcome the fear of pain and movement and retraining them using muscle stabilization and coordination.One limitation of this study is that the participants and physicians administering the intervention cannot be blinded due to the nature of the intervention. To address this issue, the assessor will be blinded. This RCT aims to evaluate the effectiveness of NRT in a real-world clinical setting. Considering that the target patient population is patients hospitalized after a TA and that these patients are generally treated through IKMT comprising acupuncture, Chuna therapy, pharmacopuncture, and herbal medicine, we used an add-on design for the interventions, where the control group will receive an IKMT while the experimental group will receive NRT in addition to IKMT. Further, to enroll patients with acute neck pain, we included TA within the past week as one of the inclusion criteria. Helping patients act normally by controlling their pain and fear would facilitate early recovery from residual pain. Consequently, NRT will be one of the viable treatment options for patients involved in a TA, which will present practical benefits for healthcare-related policy makers and clinicians.This study will shed light on the effectiveness and safety of early NRT on acute neck pain caused by a TA. Preventing the chronic progression of pain by effectively reducing pain in early stages will ensure the quick return of patients to their normal lives.Conceptualization: Suna Kim, Kyoung Sun Park, Jinho Lee, In-Hyuk Ha.Data curation: Da-Hyun Kyeong.Investigation: Suna Kim, Da-Hyun Kyeong, Min-Kyung Kim, Chang-Yeon Kim.Resources: Min-Kyung Kim.Supervision: Kyoung Sun Park, Yun Jae Lee, Jinho Lee, In-Hyuk Ha.Writing – original draft: Suna Kim.Writing – review & editing: Kyoung Sun Park, Yun Jae Lee.


Chronic pelvic pain (CPP) is an intricate condition with multiple etiologies that lead to indefinite pain mechanisms. Physicians and researchers are challenged in its treatment, and the combined therapy of pharmacologic and non-pharmacologic treatment has been recognized as a multidisciplinary approach cited by guidelines and adopted in clinical practice. As an alternative therapy for CPP, non-pharmacologic therapies benefit patients and deserve further study. This study reviews the literature published from January 1991 to April 2022 on non-pharmacologic therapies for CPP in adult women. Based on a survey, this review found that the most commonly used non-pharmacological therapies for CPP include pelvic floor physical therapy, psychotherapy, acupuncture, neuromodulation, and dietary therapy. By evaluating the efficacy and safety of each therapy, this study concluded that non-pharmacological therapies should be included in the initial treatment plan because of their high degree of safety and low rate of side effects. To fill the lack of data on non-pharmacologic therapies for CPP, this study provides evidence that may guide treatment and pain management. In severe cases, CPP, identified as a symptom rather than a disease, involves non-cyclical pain accompanied by dyspareunia and dysmenorrhea.CPP is estimated to affect 5.7% to 26.6% of women in the world.,4 In the US, CPP causes almost 15% female off-work and a 45% decrease in working productivity. CPP in the US accounts for 10% of gynecologic clinic visits and 40% of laparoscopies,,6 which cost $880 million annually. If combined with the cost of treating individual conditions related to CPP, the cost is estimated to reach $289 billion.Chronic pelvic pain (CPP) in women, defined by the American College of Obstetricians and Gynecologists, is pain derived from the pelvis, lasting for more than 6 months, which results in negative psychology, dysfunctional sexuality and behavior, and lower urinary tract symptoms.,7 According to the American College of Obstetricians and Gynecologists guidelines, CPP may be caused by multiple factors that interact with each other, including visceral etiologies, neuromusculoskeletal disease, and psychosocial status. CPP is related to both gynecological and non-gynecological disorders such as endometriosis, intra-abdominal adhesions, irritable bowel syndrome (IBS), and interstitial cystitis/painful bladder syndrome.,7,8However, the etiology of CPP is poorly understood, because not only 1 factor or disorder is attributed to pain. Pharmacologic and surgical therapies are the most popular options for treating CPP, but they are not cost effective and have always been reported to have side effects such as bloating, drowsiness, and constipation.,9,10 Current guidelines advise the use of a multidisciplinary team (MDT) approach to improve therapeutic effect.,3,7 Previous studies have noted that the early use of non-pharmacologic therapy could complement CPP treatment in terms of alleviating pain and avoiding drug addiction.,3Considering the complicated causes and limited options for CPP treatment, physicians must have to focus on reducing symptoms in advance of curing the patient completely. Meanwhile, it alleviates psychological symptoms, such as depression and anxiety.–14 A prospective study showed that more than 50% of patients with CPP are likely to pursue non-pharmacologic therapies. Therefore, this study reviews non-pharmacologic therapies for CPP in women, including pelvic floor physical therapy, psychotherapy, acupuncture, neuromodulation, and dietary therapy  focuses on mitigating tenderness of the muscles in the pelvic floor, back waist, abdominal wall and hips.,19,20 Obviously, PFPT suits the patients with pelvic floor muscle dysfunction, and is especially effective in treating recurrent tenderness in contracted pelvic floor muscles.,17,21The rationale behind PFPT is to invigorate blood flow in the pelvic floor area, ease and stretch contracted muscles, release rigid articulations, and increase elasticity of the soft tissues. As a result, pelvic floor muscle function is expected to be restored, with pain reduced as much as possible. A pilot randomized controlled trial in women with pelvic floor myalgia suggested that PFPT reduces pain more significantly than levator ani muscle trigger-point injections. Another clinical trial showed that myofascial physical therapy benefits women with pelvic floor tenderness. A randomized controlled trial concluded that group-based multimodal physical therapy based on the biopsychosocial model eases pelvic pain more significantly than primary-care physical therapy.Although clinical experience indicates that PFPT is effective, evidence-based reports are rare in the literatures.Considering the limited therapeutic effect of PFPT, patients with CPP should be advised in the initial treatment to be aware of the potential etiology, illness duration, possible delayed discomfort effect and time commitment.,24 who experience negative emotions such as depression, anxiety, catastrophizing and post-traumatic stress disorder.,24 Psychotherapy is an effective, safe, and noninvasive treatment for women with CPP that can change the cognition, mood, and behavior of patients. Cognitive behavioral therapy (CBT), a psychotherapy for CPP in women, is effective and widely used in treating chronic pain conditions .Psychological factors play an important role in triggering CPP, especially in women CBT guides patients to acknowledge pain and alter thoughts and behaviors to deal with pain.,10,26 To restructure cognitions and modify patients’ behavior or lifestyle, CBT leverages techniques such as time-based pacing, sleep hygiene, muscular relaxation, training in meditation, stress managements, and appropriate communication with physicians, friends and family.,14,25As a goal-directed psychotherapy,,28 CBT decreases the severity and frequency of pain symptoms by reducing stress and by altering catastrophic cognition. A 1-year follow-up study indicated that CBT combined with gynecologic care could reduce psychological symptoms, pain, and related dysfunction in chronic pelvic viscera and muscle,30 and the effect could last for 9 months. Similarly, a randomized controlled trial reported that psychotherapy with somatosensory stimulation reduced pelvic pain, relieved constipation, and improved the quality of life of patients with endometriosis-associated pelvic pain.Although the mechanisms by which CBT benefits patients with chronic pain are still uncertain, some studies have hypothesized that CBT changes the gray matter responsible for pain management in the brain. Mindfulness focuses on improving sensations of pain and related responses, instead of reducing pain itself. Moreover, mindfulness benefits from chronic pain, fibromyalgia, and IBS.,32–35 Another pilot study showed that 8-week mindfulness produces significant improvements in daily pain scores from baseline and thus improves the quality in CPP patients. Therefore, psychotherapy is effective in treating CPP complicated by psychological disordersBesides CBT, another psychotherapy of mindfulness could also promote tolerance of pain by reducing depression and stress in CPP patients.,37–39 In addition, acupuncture has been approved by the FDA for the treatment of tumor pain. A systematic review of 6 randomized trials showed strong evidence of the effectiveness of acupuncture in reducing pain and decreasing opioid use in patients with chronic musculoskeletal pain.Acupuncture, identified as an independent treatment modality, has been widely accepted for managing pain, including muscular and myofascial pain, lumbar and pelvic pain in primigravida, and chronic prostatitis/CPP symptom.,41 Acupuncture can balance homeostasis by stimulating sympathetic neurons and somatic afferent fibers of neurons. Acupuncture can also form a cutaneous microcurrent to promote tissue growth. Unlike morphine, which develops drug tolerance in patients with chronic pain, multiple sessions of acupuncture do not inhibit the reaction to needling. Acupuncture may promote endogenous opioid release and strengthen gate control in the pain pathways.The mechanism of acupuncture analgesia is not clear, but studies have shown that neuroendocrine, immunological, and cardiovascular reactions can be triggered by acupuncture that penetrates the peripheral system, producing mechanical signals and generating cascaded effect. Another randomized sham-controlled trial also showed that Japanese-style acupuncture is safe, effective, and non-addictive for treating endometriosis-related pelvic pain in women. Studies also indicate that Ashi acupuncture is as effective as local anesthetic injections in easing pain in women with CPP, and manual acupuncture plus usual care is more acceptable, safe, and effective than usual care alone. In addition, a randomized controlled trial concluded that neurogenic acupoint cupping, a traditional antient treatment, could significantly reduce inflammation, pelvic pain, and improve quality of life in women with CPP. These studies suggest that acupuncture is an effective and safe non-pharmacological therapy for CPP in women.A 3-arm randomized controlled pilot study concluded that meridian balance method acupuncture plus electroacupuncture treatment could relieve pain and improve physical and emotional functions in women with CPP.,47 Peripheral neuromodulation includes percutaneous tibial nerve stimulation (PTNS), transcutaneous electrical nerve stimulation (TENS), sacral neuromodulation, and pudendal neuromodulation. Peripheral neuromodulation stimulates peripheral Aβ-fibers and suppresses Aδ-fiber nociceptors, thus reduces pain. A study believes that Neuromodulation can alter nerve conduction and attenuate pain sensation by stimulating microcurrent. Central neuromodulation, such as transcranial direct current stimulation (tDCS), alleviates pain by producing microcurrents that promote neuronal excitability and activate descending inhibition systems.Various peripheral and central neuromodulation therapies have been widely studied for chronic pain control.,50,51 A prospective study showed that PTNS could decrease pain and improve quality of life in women with CPP. A randomized trial showed that PTNS is an effective therapy, with minimal invasion and a long-term efficacy of 6 months.PTNS was performed by inserting a 34-gauge needle approximately 3 to 4 cm above the medial malleolus and 1 cm posterior to the tibia, along the running direction of the tibial nerve, placing the adhesive electrode on the medial heel, and then adjusting the stimulation amplitude, typically 30 min per session for consecutive 12 weeks.,47 A prospective study showed that TENS is a safe, economical, and useful intervention for reducing pain. A feasibility study proved that TENS is effective for long-term stability.TENS suppresses pain by delivering a low voltage and low electric current from removable skin electrodes. Incorporated with pelvic floor physical therapy, TENS has been identified as the most frequently used noninvasive therapy.,53 A case report showed that sacral neuromodulation decreases the severity and frequency of CPP over a period of 19 months after implantation. A single-cohort pilot study reported that pudendal neuromodulation could relieve pain to different extents. Central neuromodulation of tDCs is usually applied in treating psychiatric conditions, but a double-blind sham-controlled crossover study showed that it benefits women with CPP by reducing pain and improving quality of life.Sacral and pudendal neuromodulation plants a programmable stimulator subcutaneously to deliver stimulation to sacral or pudendal nerves, decreasing somatic and sympathetic signals.Despite the variety of neuromodulations that relieve the symptoms of CPP, more high-quality evidence is needed to clarify its function and rationale. Patients are encouraged to consume gluten-free and anti-inflammatory foods, with low sugar and salt, meanwhile avoiding acidic or pungent foods. However, limited evidence in the literature supports its efficacy in the treatment of CPP in women. A cohort study showed that a gluten-free diet alleviates CPP in 75% of subjects over a follow-up period of 12 months. A systematic review found that persistent diet-control and clear diet intervention by experienced dieticians is critical in CPP treatment. Unlike other non-pharmacological treatments, dietary therapy is expected to be performed by patients on their own.As a self-care management regimen, dietary therapy can potentially benefit patients with CPP.In the initial treatment of CPP, it is crucial to clarify all possible etiologies because only a single etiology-treatment hardly relieves pain, which could disappoint patients and physicians. Regardless of the therapies used, pharmacologic, non-pharmacologic, or surgical therapy, no single definite approach can cure CPP; therefore, a multidisciplinary approach should be adopted.Non-pharmacologic therapy should be planned and applied initially and at each stage of CPP treatment. It is beneficial to first consider psychotherapy, as it is a representative non-pharmacologic intervention that modulates the thoughts and behaviors of patients, especially in women with negative emotions. By virtue of the specialty and safety of non-pharmacologic therapy, this study suggests introducing non-pharmacologic therapy as early as possible in treatment. Non-pharmacologic therapy contributes to a multidisciplinary approach with multiple choices of pain management. While evidence of non-pharmacologic therapy is increasing in the literature, more evidence-based studies with quantitative analysis are needed.All the authors listed have made an intellectual and substantial contribution to the work and supported it for publication.Data curation: Xinlu Wang, Yuanjie Sun.Formal analysis: Zhishun Liu.Investigation: Xinlu Wang, Hangyu Shi.Resources: Xinlu Wang, Lili Zhu.Supervision: Shuai Gao.Writing – original draft: Xinlu Wang, Zhishun Liu.Writing – review & editing: Xinlu Wang, Yu Chen, Zhishun Liu.


Introduction: The advent of laparoscopic techniques in repairing inguinal hernia has significantly improved outcomes of inguinal hernia surgery. However, acute and chronic postoperative pain after fixation of mesh with tacks and the cost of tacking devices are major hindrances to the widespread use of laparoscopic transabdominal preperitoneal (TAPP) repair in resource-poor settings. This study sought to introduce a method of mesh fixation that will reduce the cost of laparoscopic TAPP repair and might help reduce postoperative pain.Objective: To compare outcomes in the early postoperative period like pain, seroma, hematoma, urinary retention, and neuralgia after fixation with suture versus the tack fixation of mesh in laparoscopic TAPP repair of inguinal hernia. st June 2019 to 31st May 2020. A total of 144 patients between ages 18 and 60 years with an inguinal hernia on any side and having an American Society of Anaesthesiologists (ASA) score of I/II were included in this study. Patients with a recurrent hernia, large scrotal hernia, strangulated and obstructed hernias, ASA III and ASA IV, prostatism, and chronic cough were excluded. Seventy-two patients were in Group A (tack fixation group) while 72 were in Group B (suture fixation group). Separate investigators were assigned to collect pre-operative and post-operative data from both groups, recorded on specially designed proforma.Subjects and methods: This study was conducted from 1Results: The age range was 18 to 60 years with a mean age of 46.53 years ±10.01 S.D in Group A and 46.19 ±9.58 S.D in Group B. In Group A 98.6% of patients were male, and 1.4% were females while in Group B 100% of patients were male. It was found that mean pain in Group A was 4.88 ±0.887 and 5.29± 0.777 at 6 hours and 24 hours respectively. Mean pain in group B was 3.43 ±0.962 and 4.11±0.703 at 6 hours and 24 hours respectively. Moreover, mean pain in Group B was significantly less than mean pain in Group A both at 6 hours and 24 hours intervals with a p-value < 0.001. The early postoperative complications were not significantly different in both groups. Conclusion: In TAPP repair, suture fixation of mesh is less painful than tack fixation. However, there is no significant difference in the rate of other early postoperative outcomes like seroma, hematoma, urinary retention, and neuralgia. Further multicentric studies with a longer duration of follow-up are needed to validate our results. Historically, different techniques have been used in the repair of inguinal hernia. Among the many techniques introduced to decrease recurrence and complications associated with hernia repair, laparoscopic techniques have become widely available all over the world. Since the beginning of laparoscopic hernia repair in the early 1990s, many advancements have taken place leading to widespread acceptability of laparoscopic hernia repairs. As a result of the improvements in surgical techniques, prosthetic materials, and a better understanding of their use, the surgical outcome has improved significantly. The problems associated with hernia surgery are postoperative pain, prolonged hospital stay & recurrence. Compared to open surgery the laparoscopic technique is associated with a short period of stay and early return to work .TAPP  repair and TEP  repair are the two most commonly performed procedures for the repair of laparoscopic hernia. In TAPP repair, a peritoneal flap is raised after gaining entry into the abdominal cavity, and the preperitoneal space is used for placing the mesh. Different materials are used for the fixation of mesh against the anterior abdominal wall including transfascial sutures (absorbable and non-absorbable), titanium tacks, fibrin glue, and synthetic sealants, all of which have advantages and disadvantages -5. TitanSince early postoperative pain has become an important factor in the evaluation of different laparoscopic techniques, this study intends to compare early postoperative pain in tack fixation versus vicryl fixation in addition to seroma, hematoma, urinary retention, and neuralgia.During the literature review, two studies were found comparing early postoperative pain in suture fixation versus tack fixation of mesh in TAPP repair, these studies show lesser postoperative pain and analgesic consumption with suture fixation compared to tack fixation -5. The mThis study would primarily compare the early postoperative pain after suture fixation versus fixation of mesh with tack in TAPP repair in addition to other early postoperative outcomes. As there are not enough studies on this topic both in international as well as local journals, our study is intended to clarify the controversy of whether suture fixation of mesh in TAPP repair causes lesser postoperative pain or vice versa. This study was conducted in the Surgical 'C' unit, Khyber Teaching Hospital, Peshawar, from 01/6/2019 to 31/05/2020. The total sample size was 144 (72 in each group) with an allocation ratio of 1:1. The sampling technique was consecutive non-probability sampling. Institution Research and Ethical Review Board (IREB) Khyber Medical College Peshawar approved this study with an approval number 214/ADR/KMC.All patients between 18 and 60 years with unilateral inguinal hernia, diagnosed on physical examination, presenting to the Surgical 'C' unit at Khyber Teaching Hospital who opt to undergo laparoscopic hernia repair and had no comorbidity that contraindicates general anesthesia and laparoscopic surgery were included in this study. Patients with a recurrent hernia, large scrotal hernia, strangulated and obstructed hernias, American Society of Anaesthesiologists (ASA) III and ASA IV, prostatism, and chronic cough were excluded.After approval from the independent ethics committee of the Khyber Teaching Hospital, all patients meeting the inclusion criteria were admitted from OPD in the Surgical ‘C’ unit, Khyber Teaching Hospital Peshawar. A clinical diagnosis of hernia was made on physical examination. All patients with a reducible swelling in the inguinal region and positive cough impulse were diagnosed as having inguinal hernia that was confirmed on ultrasonography. The purpose of the study was explained to all patients, and written informed consent was obtained from them.A detailed history was taken from all patients followed by their clinical examination and routine investigations. All the patients were randomized into two groups by the block randomization method. Patients undergoing tack fixation of mesh were placed in group A and those undergoing suture fixations were placed in group B Figure .An investigator was assigned to collect preoperative data. All the preoperative information including age, gender, weight, years of education, and the group assigned was recorded on a predesigned proforma. A surgeon trained in advanced laparoscopy and an expert in laparoscopic TAPP repair performed the procedure.Surgery was performed using general anesthesia. Transabdominal Preperitoneal Mesh Hernioplasty (TAPP) was carried out in all patients. In this technique, three laparoscopy ports are used that give access to intraperitoneal space from where preperitoneal space is approached by raising peritoneal flaps, and dissection is done in the inguinal region to separate the hernial sac from its contents. Then mesh is applied and is fixed to the anterior abdominal wall using different techniques such as titanium tacks, fibrin glue, and sutures, and the space is closed again by stitching together the peritoneal flaps. In our study, the suture fixation group underwent mesh fixation by taking three stitches with vicryl 2/0 against the anterior abdominal wall and coopers ligament for anchoring the mesh. Taking stitches in the triangle of doom and the triangle of pain were specifically avoided. The tack fixation group underwent mesh fixation with three titanium tacks taken against the anterior abdominal wall and coopers ligament. Taking tacks in the triangle of doom and triangle of pain was specifically avoided. Post-operatively all patients were administered the same analgesics; injection ketorolac 30mg three times a day and tablet diclofenac sodium 50mg as required.Post-operative pain was compared at 6 hours postoperatively and 24 hours postoperatively by recording the mean pain score on the visual analogue scale (VAS). Data were analyzed using SPSS version 23.0 . Mean ± SD was calculated for quantitative variables like age, visual analogue score, years of education, and body weight. Frequencies and percentages were calculated for categorical variables like gender in both groups (suture fixation and tack fixation). Independent samples t-test was used to compare VAS among both groups at two different intervals (6 hrs and 24 hrs). The mean pain score of both groups was stratified by age, gender, years of education, and weight to see effect modifiers using an independent sample t-test. A p-value ≤ 0.05 was considered significant.The study had 144 participants who presented with inguinal hernia ranging in age from 18 to 60 years (mean age of 46.36 years). The study groups were found statistically similar in terms of demographics  was significantly less than the mean pain in Group A (4.88 ± 0.887). The mean postoperative pain score at 24 hours in group B (4.11± 0.703) was also significantly less than that in Group A (5.29 ± 0.777)  repair and totally extraperitoneal (TEP) repair are the two commonly used laparoscopic techniques of inguinal hernia repair. After dissecting the hernia sac, both techniques use the preperitoneal space for mesh placement. Thereafter, the mesh is secured against the anterior wall of the abdomen. The crucial step in an inguinal hernia repair is the fixation of mesh which is associated with vascular and neurological complications ,17. MostBased on the findings in the above citations, it is evident that postoperative pain and neuralgia can be expected after TAPP repair. In order to tackle the problem of postoperative pain and neuralgia after fixation of mesh with titanium tacks, different methods are being used such as changing the orientation of endotacker to vertical while placing tacks and applying a smaller number of tacks ,17,28. FIn our study, we compared pain following suture fixation of the mesh versus tacker fixation. In our study, the early postoperative pain was found to be significantly less in suture fixation as compared to tack fixation (p<0.001). This proved our hypothesis that the mean pain after suture fixation and tack fixation are not equal. Another study by Kleidari et al. showed that the in-hospital mean pain score recorded on the morning after surgery was not significantly different between suture fixation and tacker fixation. However, Kleidari et al. found that mean pain at day one and day six after discharge was significantly less in the suture group than in the tacker group which supports our findings . AnotherOguz et al. reported that the statistical comparison of the patients in whom tacker was used for fixation did not affect VAS 1 (VAS on the first postoperative day). Conversely, VAS 1 was significantly lower in patients where sutures were used for peritoneal closure than in patients where tacker was used for peritoneal closure (p = 0.027) . The finOn the other hand, studies comparing fixation of the mesh with suture against tack fixation in ventral hernias showed no difference in postoperative pain between the suture and tack fixation p=0.38 ,10.Strengths and limitationsThe strength of our study is that no significant difference existed between the two groups with respect to age, sex, weight, educational status, and the number of tackers used for mesh fixation. Also, our study was double-blind with neither the patient knowing which technique they underwent nor the investigators as different investigators were assigned to collect preoperative and postoperative data. Also, a single surgeon was assigned to carry out all the operations, so that the operative technique and surgical skill of the surgeon did not act as an effect modifier.The limitation of our study is that it is a single-centered study. Also, the sampling technique used was non-probability consecutive sampling. Moreover, while comparing the mesh fixation methods, only early outcome variables were studied.In laparoscopic transabdominal preperitoneal repair, suture fixation of the mesh is less painful than tack fixation of the mesh. However, there is no statistically significant difference in the rate of other early postoperative complications. Further multicentric studies with a longer duration of follow-up are needed to validate our results. In addition, other important outcome variables such as chronic pain, hernia recurrence, and incidence of mesh migration need to be compared in both techniques.