Functional near-infrared spectroscopy (fNIRS) allows for ongoing measures of brain functions during surgery. The ability to evaluate cumulative effects of painful/nociceptive events under general anesthesia remains a challenge. Through observing signal differences and setting boundaries for when observed events are known to produce pain/nociception, a program can trigger when the concentration of oxygenated hemoglobin goes beyond ±0.3 mM from 25 s after standardization.fNIRS signals were retrieved from patients undergoing knee surgery for anterior cruciate ligament repair under general anesthesia. Continuous fNIRS measures were measured from the primary somatosensory cortex (S1), which is known to be involved in evaluation of nociception, and the medial polar frontal cortex (mPFC), which are both involved in higher cortical functions (viz. cognition and emotion).A ±0.3 mM threshold for painful/nociceptive events was observed during surgical incisions at least twice, forming a basis for a potential near-real-time recording of pain/nociceptive events. Evidence through observed true positives in S1 and true negatives in mPFC are linked through statistically significant correlations and this threshold.Our results show that standardizing and observing concentrations over 25 s using the ±0.3 mM threshold can be an arbiter of the continuous number of incisions performed on a patient, contributing to a potential intraoperative pain load index that correlates with post-operative levels of pain and potential pain chronification. Capturing repeated nociceptive events (pain caused by damaged body tissue) during surgery may provide a method for improving analgesia during surgical procedures under general anesthesia. Such data would also provide better strategies of reducing postoperative pain based on the assumption that repeated nociceptive barrages during surgery, if not abated, likely lead to central sensitization and an increased potential for postsurgical chronic pain . An estiOur prior work has reported that we can capture brain measures of nociceptive events under general anesthesia using functional near-infrared spectroscopy (fNIRS) . The sigHere, we evaluated patients undergoing anterior cruciate ligament (ACL) repair during which multiple surgically induced damaging events (e.g. trauma to nerves and tissue) produced nociceptive “barrages.” We used a threshold approach, which can detect when a patient is undergoing a painful event—even when in an analgesic state. Through observing differences in signals and setting boundaries for when pain events occur, an automated alert can trigger whenever the concentration of oxygenated hemoglobin (HbO) exceeds ±∆0.3 mM after standardization within 25 s can emerge  assented and consented for participation in this study.Study personnel recorded data from 24 patients, ages ranging from 12 to 25 years, who underwent arthroscopic knee surgery under general anesthesia. Five of the 24 patients were excluded from analysis for the following reasons: 1 patient’s dataset did not save; 1 patient withdrew due to medical emergency, and 3 patients had incomplete pre- and/or postsurgical data. Anesthetic data for each patient is shown in Eleven patients (58%) received regional anesthesia via adductor canal peripheral NB ropivacaine (0.2% or 0.35%) via ultrasound guidance on the ipsilateral limb. A more detailed description of regional anesthesia is given in Table 2. A catheter for infusion of local anesthetic was given to patient #17 after 6 h of surgery. A lateral femoral cutaneous NB was added to the adductor canal block in patient #5. Dexmedetomidine and clonidine supplemented ropivacaine in 1 (#7) and 2 (#s 5 and 9) patients, respectively.n = 9) or just after surgery has finished (n = 7). Ten of the 11 patients who received regional anesthesia via NB were given local anesthetic by the operating surgeon with incision (n = 8) or at the end of surgery (n = 2). Six of the 8 patients who did not receive a NB were given local anesthetic at the end of surgery.Local anesthetic  was administered by the operating surgeon in 16 patients (84%), either just before incision  was used to collect data. Changes in concentration of oxygenated (HbO), deoxygenated (HbR), and total (HbT) hemoglobin within cortical regions of interest (ROIs) were measured following the modified Beer–Lambert Law. Our group has previously described techniques for using fNIRS to measure pain/nociception under general anesthesia  and a siWe used an electroencephalography (EEG) cap to design a custom probe with a 10–20 layout to include 24 channels covering the bilateral prefrontal cortex and the bilateral somatosensory cortices. This probe consisted nine sources and 14 long-separation detectors (placed ~3 cm from the source) and 9 short-separation detectors (placed 0.8 cm from the source) ; see FigBefore entering the operating room, study staff placed the cap with probes on the patients’ heads.  A 10-min baseline scan in the preoperative setting confirmed optimal data quality and optode positions. fNIRS data were continuously collected intraoperatively, starting at anesthetic induction, and ending after final suturing at the conclusion of surgery. During this period, 1 research personnel monitored fNIRS data acquisition quality and another noted the time and type of surgical procedures. For example, the initial incision was noted down as “incision,” arthroscopic scraping was noted as “scraping,” and so on. All sources are set at the standard/power intensity at 80 dB using continuous wave 6 software. After calibration, the acquisition software indicates the concentration coming from the optodes. The light sensitivity is then adjusted to give a good signal, deemed acceptable when a certain threshold is passed. We visually confirm that there is visible contact with the scalp by ensuring that there is a heart rate between 1 and 1.5 Hz at ~60 bpm.Raw fNIRS time series data was preprocessed using scripts written in-house by our group in the MATLAB R2018b platform. We used a wavelet-based algorithm  to conveAfter preprocessing, each fNIRS channel is kept distinct for HbO, HbR, and HbT, observing which channels represent the contralateral and ipsilateral areas of mPFC and S1. Concentrations are reported every 0.04 s whose mean is taken every second to be consistent with the timings of when incisions are reported during surgery in the training stage. Of the 19 available patients, 15 are examined in this stage, while the remaining 4 form the test set that can judge the effectiveness of the algorithm. No power analysis was performed as this is a pilot study.x-axis. This window is then moved by 1 s each time until the end of surgery. If a time point corresponded with a surgical event, that point was placed in a separate “pain” set, while the remainder were left in a “nonpain” set.From the original channels, concentration changes are observed across every second from the start of operation. Hemoglobin concentration values are recorded every 0.04 s, which are then averaged into single seconds for further processing. A 10-s sliding window is then formed. From the start of surgery, the first 25 s are standardized and are then observed for maxima/minima, correlations with other channels, and area formed between the curve and the t-tests were conducted within each group and the intersection between the pain set and the center of the nonpain set. These tests were performed at the P < 0.05 significance level, with a further false-discovery rate correction for multiple comparisons at α = 0.05 when noted.The pearson’s R correlation coefficient is calculated for every second in the “pain” and “nonpain” sets, as shown in The patient timelines, shown in In past research, evoked stimuli are observed after painful events. In most cases, ∆[HbO] increases from the baseline to at least 0.3 mM, reaching our predefined threshold. The results observed through S1 do not contradict this, where the majority of first and second incisions performed on the patient provides a larger change in ∆[HbO] concentration.  are subjective. Furthermore, as noted in prior reports, there is increasing evidence that afferent nociceptive signals may continue reach the brain  As such,The real-time evaluation method used here and in our prior work related to measures of pain/nociception is using fNIRS  ImportanA spontaneous, real-time algorithm that returns feedback on deviations from the analgesic state is possible through assessing fluctuations in oxygenated and deoxygenated hemoglobin during pain. The ±∆0.3-mM threshold assigned in prior research is shown to remain effective under continuous observation while taking the negative border into account. This threshold was observed through examining what ∆[HbO] changes correspond to pain signals during surgery. This was observed for at least 2 different incisions for each patient in the training set against a control period taken furthest away from any point in time where a “painful” event is conducted. From The morphological quantities recorded in the standardized time window can then be separated based on the records of when pain does and does not occur, mitigating any potential spurious results. This 25-s window provides the maximum delay between the observation of pain events and their capture in real time such that the surgical team receives information about the state of the patient less than half a minute after procedures have occurred. State distinction requires observing small/discrete changes in hemoglobin concentrations and their correlations, which leads to the development of a robust pain detector. However, there remains a high margin of error in these current experiments. Future work will mitigate this by analyzing further signal variance through increasingly precise measurements, reducing the false positive rate (shown in the test set in The work presented here was mapped to a test set with varying degrees of success; further threshold sensitivity research can provide a stronger case for real-time pain capture. The notion that nociceptive stimuli may be captured in the unconscious anesthetized or sedated state using fNIRS is supported by our prior data relating to signals obtained for evoked pain/nociception . Here, wPaper_Border_Green_220420_SG_CerebralCortex_SupplementaryMaterial_tgac019Click here for additional data file.


Patients were divided into two groups using the random number table method, TPVB group (n = 60) and normal saline group . Two-point nerve block was performed at T5-6 and T6-7 levels. Patients in the TPVB group received nerve block with 15 mL of 0.375% ropivacaine hydrochloride, while those in the control group received 5 mL of 0.9% normal saline. The numeric rating scale (NRS) scores at rest and during movement at 24 and 48 hours after surgery and the number of times the button on the patient-controlled analgesia pressed at 24 h after surgery in two groups were recorded. All patients were followed up by outpatient visits or phone visits at 1 year after surgery and assessed using Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale and Hospital Anxiety and Depression Scale (HADS). According to the inclusion, exclusion, and drop-out criteria, 108 patients were finally included, with 52 patients in the TPVB group and 56 patients in the control group. There was no statistically significant difference between the two groups in terms of age, sex, height, body weight, body mass index, ASA classification, and operation time (P > 0.05). NRS pain scores at 24 h (P = 0.0108) and 48 h (P = 0.0000) after surgery, the number of times pressing patient-controlled analgesia at 24 h after surgery (P = 0.0000), the LANSS scores (P = 0.0000), HADS anxiety score (P = 0.0000), and depression scores (P = 0.0000) at 1 year after surgery in the TPVB group were both significantly lower than those in the control group. To sum up, ultrasound-guided TPVB can effectively relieve pain at 48 hours after thoracoscopic lung cancer radical surgery and chronic postoperative pain at 6 months after V thoracoscopic lung cancer radical surgery.This study is aimed at investigating the effect of thoracic paravertebral block (TPVB) on the occurrence of chronic postoperative pain, postoperative anxiety, and depression in patients undergoing thoracoscopic radical lung cancer surgery. A total of 120 patients who underwent thoracoscopic radical lung cancer surgery in our hospital from June 2019 to March 2021 were included. There were 62 males and 58 females, with an age of 18-75 years old and a body mass index of 20-28 kg/m Pain is one of the most important causes of stress in patients undergoing surgery, which can lead to increased postsurgical stress response and various cardiovascular and cerebrovascular complications and affect the quality of life of patients following surgery . For patLung cancer is one of the most common malignant tumors all over the world, with high mortality and morbidity and a tendency to metastasize, which threatens human health and life . ThoracoThe analgesic effect of thoracic paravertebral block (TPVB) is similar to that of epidural analgesia, which can obviously reduce the incidence of chronic postoperative pain in patients undergoing thoracoscopic radical resection of lung cancer ; there aThis study investigated the effect of TPVB on the occurrence of chronic postoperative pain, postoperative anxiety, and depression in patients undergoing thoracoscopic radical lung cancer surgery, so as to provide a reference for clinical promotion of TPVB and enhancement of chronic postoperative pain management.This was a double-blind randomized controlled study. This study was approved by the ethics committee of our hospital . Written informed consent was obtained from all patients included in the study. This study complied with the Declaration of Helsinki and adheres to CONSORT guidelines.2, American Society of Anesthesiologists (ASA) I or II, operative time of <4 hours, and no surgical history, as well as no history of psychiatric and neurological diseases. Exclusion criteria were as follows: aged ≥76 years, allergy to anesthetic drugs, puncture site infection, history of chest surgery or trauma, history of chronic pain, and history of psychiatric and neurological disorders, including depressive or anxious tendencies. Drop-out criteria were as follows: patients who were lost to follow-up patients who were unable to cooperate properly with assessment, and patients who received other surgical treatment during follow-up.A total of 120 patients who thoracoscopic lung cancer radical surgery in our hospital from June 2019 to March 2021 were included. The inclusion criteria were as follows: patients who were aged 18-75 years with body mass index of 20-28 kg/mμg/kg), rocuronium (0.6 mg/kg), and sevoflurane (1–1.5%) calculated based on patients' body weight, and then, bronchial intubation was performed. After patients were turned to the lateral decubitus position, the position of the T5 spinous process was determined by manual palpation, the ultrasound probe was oriented vertically perpendicular to the midline and then moved upward to check the spinous process and confirm the structures, such as transverse process and pleura. After routine disinfection, two-point nerve block was performed at T5-6 and T6-7 levels, it is needed to confirm that the tip of the nerve block needle passed through the costotransverse ligament and entered in the paravertebral space, and there was no blood return after pulling back. For patients in the TPVB group, 15 mL of 0.375% ropivacaine hydrochloride was slowly injected at the two points. For patients in the control group, 15 mL of 0.9% normal saline was slowly injected [Patients were divided into two groups using a random number table: TPVB group and normal saline group (control group). All procedures were performed by a senior attending physician who had more than 5 years of experience in TPVB and completed more than 50 cases of TPVB alone. The physician was unaware of treatment assignments. The injectable drugs are prepared by a physician before the procedure. None of patients received preconditioning before entering the operating room. After patients entered the operating room, vital signs were monitored routinely, including heart rate, blood pressure, oxygen saturation (pulse oximetry), invasive arterial blood pressure, and bispectral index (BIS) . All patAfter surgery, all patients were treated with intravenous patient-controlled analgesia  for postoperative analgesia. The PCA was set as a basal infusion rate of 2 mL/h, a bolus dose of 2 mL, with lockout time of 15 min. When pain control was not satisfactory, patients were encouraged to self-administer bolus doses of medication by pressing the PCA button. If postoperative pain is still not effectively relieved, additional nonsteroidal analgesic drugs can be administered; if the pain is still not relieved, consultation with an anesthesiologist may be necessary .The numerical rating scale (NRS) pain scores at rest and during movement and the number of times the button on the PCA pressed at 24 h and 48 h after surgery were recorded. All patients were followed up by outpatient visits or phone visits at one year after surgery and analyzed using the LANSS scale and HADS. A LANSS score of ≥12 indicates the presence of neuropathic pain, and further treatment for chronic pain is recommended for such patients. A score of ≥11 on either HADS depression subscale (HADS-D) or anxiety subscale (HADS-A) indicates the presence of anxiety and depressive symptoms . Throught-test. Continuous variables with a skewed distribution are expressed as median (M) and interquartile ranges (IQR). Categorical data are expressed as number and percentages. Differences between groups were analyzed with the chi squared (χ2) test or Fisher's exact test. P < 0.05 was considered to indicate a statistically significant difference.Statistical analysis was carried out using SPSS software . Continuous variables with normal distribution are expressed as the mean ± SD, and comparisons between groups were conducted by using two independent sample A total of 120 patients were initially enrolled in this study. According to the aforementioned inclusion, exclusion, and drop-out criteria, 108 patients were finally included, with 52 patients in the TPVB group and 56 patients in the control group. Analgesia was generally satisfactory in patients of the TPVB group within 48 hours after surgery, and no patients required consultation with an anesthesiologist due to inadequate analgesia within 48 h after surgery.P > 0.05, There was no statistically significant difference between the two groups in terms of age, sex, height, body weight, body mass index, ASA classification, and operation time  in the TPVB group at 1 year after surgery was significantly lower than that in the control group  was significantly lower in the TPVB than in the control group at 1 year after surgery (P > 0.05). It has been reported that TPVB can effectively relieve postoperative pain in patients undergoing thoracoscopic radical lung cancer surgery, which provides good analgesia [P = 0.0108, P = 0.0000, P = 0.0000, and P = 0.0002). At 24 h after surgery, the number of times pressing PCA was also significantly reduced in the TPVB group compared with the control group (P = 0.0000).In this randomized, double-blind, controlled study, we compared patients' baseline characteristics and found that there was no statistically significant difference between the two groups in terms of age, sex, height, body weight, body mass index, ASA classification, and operation time .During one-year postoperative follow-up by outpatient visits or phone visits, we also used the LANSS scale and the HADS to assess the occurrence of neuropathic pain, anxiety, and depression, respectively, in patients of the two groups. The LANSS scale is the most commonly used reliable scale for diagnosing the degree of neuropathic pain in different diseases, the specificity reached a high of 93%, and sensitivity reached a high of 83% . In our Numerous studies have shown that TPVB can reduce postoperative pain in patients undergoing thoracoscopic radical resection of lung cancer, and the underlying mechanism has also been widely discussed. More studies choose to perform TPVB before induction of general anesthesia in patients, which can not only ensure safety during surgery and avoid serious complications but also allow determination of blocking range and exclude cases with poorer outcomes, making the conclusions more accurate . In ordeThe possible mechanisms underlying neuropathic pain include the follows: damaged nerve fibers caused by demyelination generate spontaneous and continuous ectopic discharges, resulting in peripheral sensitization; abnormal neural electrical activity continues to be transmitted to the central nervous system, leading to central sensitization . Local pChronic pain can affect patients not only physically but also mentally. In this study, the HADS was used to assess the occurrence of anxiety and depression in patients at 1 year after surgery. The results showed that the incidence of anxiety or depression was significantly higher in patients who did not receive TPVB compared with those who received TPVB. However, considering that many factors may contribute to the occurrence of anxiety and depression, evidence is inadequate to support the causal relationship between the incidence of anxiety, depression, and the incidence of neuropathic pain, as well as the use of TPVB during surgery; further investigations are needed to confirm this finding.The study still has some limitations. First, the mechanisms of chronic postoperative pain and pathological pain are complex, which can be influenced by many factors . TPVB caOur findings showed that general anesthesia combined with TPVB could significantly reduce postoperative pain in patients undergoing thoracoscopic radical lung cancer surgery. Our findings also showed that TPVB could significantly reduce the incidence of neuropathic pain, as well as the incidence of anxiety and depression symptoms at 1 year after surgery. Our findings had implications for improving clinical application of TPVB and enhancing postoperative pain management.


BackgroundStatin, a hydroxymethylglutaryl-coenzyme A reductase inhibitor, is one of the commonly used lipid-lowering drugs that is used for lowering lipid levels in the body. Muscle pain is a commonly reported adverse effect of statins, yet little is known about the prevalence of muscle pain and statin use in the general population.MethodsThe cross-sectional study was conducted in National Guard Hospital, Riyadh, Saudi Arabia. All study subjects were adult statin users aged 18 years old or above. A total of 313 patients were included in the study. The study was conducted based on a questionnaire distributed among patients according to inclusion and exclusion criteria.ResultsAmong 313 statin users, patients underwent cardiac catheterization , stress test , percutaneous coronary intervention , and coronary artery bypass graft , while 203 patients didn’t have any intervention (64.9%). Most of the study subjects were on atorvastatin .The prevalence of muscle pain was 73.5%; 95% CI = (68.4% - 78.1%). The most common sites of pain were lower limb pain , upper limb pain , and trunk pain . The common types of pain were joint pain , muscle weakness , muscle aches , and muscle cramps ; and patients who reported that they stopped statin at some point because of muscle pain were 92 (29.4%).ConclusionStatins are important for managing and preventing ischemic heart diseases. Our study found that muscle pain is highly associated with statin use with a prevalence of 73.5%, which causes many patients to tend to stop taking their medication. Therefore, preventing the side effects by adjusting the proper dose or switching to another type of statin for high-risk patients will help them to continue using the drug. Also, it is important to rule out secondary causes of myopathy such as physical activity, fracture, thyroid dysfunction, or infection. Ischemic heart disease (IHD) is a common and important disease that must be controlled. Ischemia is defined as a "restriction of blood flow and thus oxygen in a part of the body due to narrowing of the blood vessel." . CoronarNowadays statin is considered standard practice for management after acute coronary syndrome, regardless of lipid levels . Statin,Globally, there are few studies exploring this problem , 16. ForThere are many details required to be covered in the future, including identifying the dosage of statins that triggers muscles pain. Moreover, there are many subtypes of statin, so we must discover which subtype causes more serious muscle pain than others, and also whether muscle pain is associated with other comorbidities unrelated to statin use or not. These points may be used for the initiation of new studies in the future. Because there is a lack of research in Saudi Arabia about this problem, we are conducting this research to determine the prevalence of self-reported muscle pain among statin users attending National Guard Hospital, Riyadh. Moreover, we will assess the compliance of statin due to self-reported muscle pain, and we will determine which musculoskeletal regions are affected by statin muscle pain.Study design and area and settingsThis is a cross-sectional study to measure the prevalence of self-reported side effects of statins amongst the selected population, conducted in National Guard Hospital, Riyadh, Saudi Arabia.Identification of study participantsThe study about the prevalence of self-reported muscle pain included 313 patients who were using statins. It included patients on statins who were above 18 years of age with or without cardiac intervention such as cardiac catheterization, coronary artery bypass grafting (CABG), or percutaneous coronary intervention (PCI). We used the non-probability convenient sampling method as we had chosen our study population according to certain characteristics.Data collection processThe data was collected using a self-administered questionnaire to patients who are using statins and attending the National Guard Hospital. The questionnaire contained different types of questions to determine the prevalence of a specific side effect of a drug, which region of the body is more susceptible, which drug is being used, and how many patients have stopped using the drug due to this side effect. The questionnaire contained 14 questions, and they were translated into Arabic by group members. The questionnaire was reviewed by experts in the cardiac clinic to test for its content validity and reliability. Also, we used in our questionnaire some questions from Statin Experience Approved Questionnaire . After tData analysisData was entered and analyzed using SPSS Statistics v. 24.0 . The descriptive statistics were presented as frequency and percentage for the categorical variables e.g.  and the mean ± SD for numerical variables. Chi-square was used for the association between body pain and patients’ characteristics. A test was significant if p-value < 0.05.The questionnaire responders were N=313; 163 52.1%) were males and 150 (47.9%) were females . The most common sites of pain were lower limb pain , upper limb pain , and trunk pain  . Around 76.7% of female statin users and 70.6% of male statin users reported pain. This means that statin-induced myopathy is slightly more prevalent in females. In comparison to our study, there is another cross-sectional study done in 2018 which studied the prevalence of statin-induced myopathy at Punjab Institute of Cardiology, Lahore, Pakistan. The results showed that 51% of patients were myalgic . In addiNowadays statin is considered standard practice for management after acute coronary syndrome regardless of lipid level . Statin This present study shows that patients on statins have muscle pain in various body parts, manifesting most commonly in the lower limbs, upper limbs, trunk, and back. The symptoms vary in severity from mild to moderate to severe muscle pain. Other symptoms reported are muscle cramps, muscle weakness, and joint pain.Among statin users, we included patients that had one or more of these interventions, namely cardiac catheterization, stress test, percutaneous coronary intervention, coronary artery bypass graft, or those who didn’t have any intervention. A minority of patients reported that they stopped statin at some point because of muscle pain; this may affect their adherence to the medications, consequently leading to abnormalities in their cholesterol levels.Statin is important for managing and preventing ischemic heart diseases. Muscle pain is highly associated with statin use with a prevalence of 73.5%. As a result, patients tend to stop taking their prescribed medications. Therefore, preventing the side effects by adjusting the proper dose or switching to another type of statin for patients at high risk will help them to continue using the drug. Also, it is important to rule out secondary causes of myopathy such as physical activity, fracture, thyroid dysfunction, or infection.


Hypertension and thyroid nodules (TNs) are common medical problems that are increasing in prevalence globally. Hence, we conducted this study to assess the prevalence and associated predictors of hypertension in adult patients with TNs at the Royal Commission Hospital, Kingdom of Saudi Arabia (KSA).A retrospective study was conducted between 1 January 2015 and 31 December 2021. Patients with documented TNs based on the Thyroid Imaging Reporting and Data System (TI-RADS) were recruited to assess the prevalence and associated risk factors for hypertension.2. There was a high prevalence of hypertension (22.5%) in adult patients with TNs. In the univariate analysis, there were significant associations between diagnosed hypertension in patients with TNs and age, sex, diabetes mellitus (DM), bronchial asthma, triiodothyronine (FT3), total cholesterol and high-density lipoprotein (HDL). In the multivariate analysis, age (OR = 1.076 [95% CI 1.048 – 1.105]), sex (OR = 2.28 [95% CI 1.132 – 4.591]), DM (OR = 0.316 [95% CI 0.175 – 0.573]) and total cholesterol levels (OR = 0.820 [95% CI 0.694 – 0.969]) were significantly associated with hypertension.Three hundred ninety-one patients with TNs were recruited for this study. The median  age was 46.00 (20.0) years, and 332 (84.9%) of the patients were females. The median (IQR) body mass index (BMI) was 30.26 (7.71) kg/mThere is a high prevalence of hypertension in patients with TNs. Age, female sex, DM and elevated total cholesterol are significant predictors of hypertension in adult patients with TNs. A very high prevalence (50%) of TNs larger than 1 cm in patients without previously diagnosed thyroid disease has been documented in autopsy data . Althoug2.A retrospective study was conducted at the Royal Commission Hospital from 1 January 2015 to 31 December 2021. The files of adult patients (men and women) aged 18 years and older with documented TNs based on the findings of an ultrasound procedure were retrieved. The ultrasound procedures were conducted in the radiology department of the hospital. Each thyroid ultrasound procedure was performed in the radiology department by a radiology specialist, and each report was reviewed and approved by a radiology consultant. Thyroid ultrasound reports based on the American College of Radiology Thyroid Imaging Reporting and Data System (TI- RADS) were adopted to assess the TNs  28]. Me. Me28]. 2.12.1.1TNs were diagnosed according to the ACR TI-RADS classification criteria for risk assessment of malignant TNs .2.1.2BMI was calculated as the body mass divided by the square of the body height; it is expressed in units of kg/m², resulting from mass in kilograms and height in metres.2.1.3This variable included patients known to be hypertensive and receiving treatment according to their medical records during the time the thyroid ultrasound was conducted.2.1.4This variable includes those who had documentation of DM (type 1 and 2), whether they were on diet control or glucose-lowering drugs during the time of the thyroid ultrasound procedure.2.1.5This variable included patients diagnosed with bronchial asthma based on their medical records around the time of the thyroid ultrasound procedure.2.1.6This variable was defined as a 25-hydroxyvitamin D (25[OH]D) level of < 30 ng/mL; levels equal to or above this cut-off point were considered normal .2.2Data were analysed using SPSS for Windows (version 22.0). The Shapiro-Wilk test assessed the normality for continuous data; all variables were not normally distributed. Data were expressed as proportions, medians with interquartile ranges (IQRs) or numbers and proportions, as applicable. A univariate analysis was performed, with the diagnosed hypertension as the dependent variable. The independent variables were age, sex, BMI, thyroid status, DM, bronchial asthma, thyroid hormones, 25(OH)D level, haematological indices , lipid profile and TI-RADS ultrasound score. A variable was analysed using logistic regression if its univariate P-value was < 0.20, and backward stepwise likelihood ratio regression was selected for adjustment. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed, and P-values < 0.05 were considered significant.3.2 and 14.50 (12.0) nmol/L, respectively. The median (IQR) values for the thyroid hormones were as follows: thyroid-stimulating hormone (TSH), 1.72 (2.43) mmol/L; free thyroxine, 1.12 (0.45) ng/dL; and FT3, 2.69 (0.40) nmol/L. While most participants had normal thyroid functions (64%), a small percentage of patients had either hypothyroidism (28.6%) or hyperthyroidism (7.4%). The median (IQR) for total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides were 5.80 (3.89) mmol/L, 3.76 (0.80) mmol/L, 2.99 (1.71) mmol/L and 1.78 (1.11) mmol/L, respectively. The median (IQR) values for the haematological indices were as follows: white blood cell count, 7.01 (2.63) 109/L; haemoglobin, 12.60 (1.7) gm/dl; and platelet count, 276.15 (95.8) 103/dl. The patients’ percentages according to the TI-RADS ultrasound scores  were 2.6%, 18.4%, 40.7%, 36.3% and 2%, respectively (Three hundred ninety-one patients with documented TNs were recruited for the study. The median (IQR) for the patients’ age was 46.00 (20.0) years, and the majority were females (84.9%). The median (IQR) for the BMI and 25(OH)D level were 30.26 (7.71) kg/mectively . There wIn the univariate analysis, there was no association between diagnosed hypertension in adult patients with TNs and BMI, 25(OH)D level, thyroid status, haematological indices , LDH, triglycerides, TSH, FT4 and thyroid ultrasound based on the TI-RADS scoring system. However, there were significant associations between diagnosed hypertension in adult patients with TNs and age (OR = 1.099 [95% CI 1.073 – 1.127]), sex (OR = 3.14 [95% CI 1.750 – 5.634]), DM (OR = 0.160 [95% CI 0.095 – 0.27]), bronchial asthma (OR = 0.495 [95% CI 0.227 – 1.077]), FT3 (OR = 0.666 [95% CI 0.468 – 0.948]), total cholesterol (OR= 0.645 [95% CI 0.559 – 0.745]) and HDL (OR = 0.420 [95% CI 0.316 – 0.558]), In the multivariate analysis, bronchial asthma, FT3 and HDL were not significantly associated with diagnosed hypertension in adult patients with thyroid nodular diseases. However, there were significant associations between hypertension in adult patients with TNs and age , sex , DM  and total cholesterol levels  see .4.The current study documented a higher prevalence of hypertension (22.5%) in adults with thyroid nodular diseases in the KSA. The prevalence of hypertension in patients with TNs in this study was higher than that obtained recently in the KSA 16.8%)  and slig.8%  and 5.This study was retrospective and involved only one centre. Other factors, such as thyroid antibodies, iodine levels, blood pressure control, duration of hypertension, nutritional patterns, smoking, alcohol consumption, exposure to radiation, genetic analysis and environmental factors, were not assessed.6.There is a high prevalence of hypertension in adult patients with thyroid nodular disease. Age, female sex, DM and a high level of total cholesterol are significant predictors of hypertension in patients with TNs in the eastern region of the KSA.


Complete relief of pain due to irreversible pulpitis is challenging to obtain with analgesic medications. The high incidence of an inferior alveolar nerve block (IANB) failure makes it difficult for practitioners to perform endodontic treatment without implementing other anesthetic techniques, especially mandibular molars. The aim of this study was to compare efficacies of two different quantities of paraformaldehyde based pulpal medicaments to relieve the pain and control hyperemic pulp post-failure of IANB and supplementary technique in patients experiencing this symptomatic irreversible pulpitis in the permanent mandibular tooth.Eighty-two participants with severe pain pre-operatively  were enrolled, and pain responses were recorded at different time intervals using the Heft Parker visual analogue scale. To the patients experiencing pain even after the administration of the standard IANB and supplemental intraligamentary injection, one of the two paraformaldehyde based pulpal medicaments was placed in the pulp chamber and sealed. Participants were recalled after 24–48 h (second visit) to assess pain and bleeding reduction.p < .05). Hence judicious use within a recommended period, pulpal medicaments can be considered safe.Results showed a significant decrease in pain severity and bleeding score post medicament placement (Paraformaldehyde based pulpal medicament can be used as an alternative to manage pain in patients having severe irreversible pulpitis and hyperalgesia. Adequate local anesthesia (LA) is crucial in dental treatment, especially in managing irreversible pulpitis. Posterior teeth are routinely anesthetized in the mandibular arch using the inferior alveolar nerve block (IANB) technique. Unfortunately, IANB is proven to have substantial failure rates ranging between 43%–83% . The reaThese failures may be overcome by administering supplementary techniques . AlthougThe American Association of Endodontists divides pulpotomy/pulp amputation into necessary amputation and mortal/devitalization/mummification/amputation . The mumTo the best of the authors’ knowledge, there are no documented cases of systemic distribution of formocresol in humans. Hence, in the present investigation two pulpal medicaments containing different quantities of paraformaldehyde with lidocaine are used to compare its efficacy after the failure of IANB and supplemental intraligamentary injection in patients experiencing symptomatic irreversible pulpitis in the permanent mandibular tooth.This study was designed as a prospective, two-arm, parallel-group, double-blind, randomized clinical trial that adhered to the Consolidated Standards of Reporting Trials (CONSORT) guidelines . The resThe study was conducted in the Department of Conservative Dentistry, and Endodontics and patients were allocated into two groups with an allocation ratio of 1:1. All included patients  signed ahttps://biostat.app.vumc.org/wiki/Main/PowerSampleSize).With a type I error of 0.05 and statistical power of 80%, the minimum sample size was 60 participants to categorize a clinically significant difference of 30% in post-endodontic pain and bleeding incidence between the experimental groups. The number was escalated to 82 candidates participating in this investigation to account for exclusions and dropouts. Power and sample size calculation were estimated using PS software Version 3.1.2 (The diagnosis of symptomatic irreversible pulpitis was made based on the following: (a) patient’s chief complaint of severe pain that was sharp, piercing or shooting in nature, lingers even after the hot or cold stimulus and subsiding on intake of medications. (b) Patients giving a history of nocturnal pain and referred pain to the ear and with the clinical examination of deep caries and radiographic examination of radiolucency involving enamel, dentin and pulp with no peri-apical radiolucency. Pre-operative (PO > 114 mm) pain response of 82 patients was recorded using the VAS  by the iA standard IANB of 1.8ml was administered by investigator LM to 82 patients using 0.55 × 25 mm/24 × 1needle size, 2 ml syringe  and 2% lidocaine with adrenaline . The access cavity preparation under a rubber dam was initiated after fifteen minutes of anaesthesia administration using Endo Access bur  and Endo-Z bur .The operator RB blinded to the present study, continued endodontic treatment for patients who recorded no pain either to the IANB or IANB with intralingamentary injection. The adjuvant supplemental intraligamentary injection of 0.2 ml on each side of the tooth  was administered with ligajet intraligamentary jet injector (Micro Mega) using 30 gauge needle and cartridge containing lignocaine hydrochloride 2% with adrenaline 1:80000 by the investigator LM. The needle was inserted in the periodontal ligament and advanced until resistance was felt. Only those patients who failed to obtain pulpal anesthesia and still experienced pain or discomfort during access cavity prepration, the case was transferred to the principal investigator (NS) and was included in the trial.The patient was assigned randomly to one of two study groups: Group C  or Group D  using Excel software . Caustinerf by Septodont  and D-Pulp by Ammdent contain lidocaine and paraformaldehyde in its composition. However, the quantities of paraformaldehyde in D-Pulp is 460 mg in 1gm and in Caustinerf it is 180 mg in 1 gm. In both groups, after recording the bleeding score or BS1 , the minuscule quantity of Caustinerf or D-pulp was placed in the pulp chamber. Next, the tooth was sealed with the premixed thick zinc oxide-based temporary filling material . The patient was advised to take an analgesic medicament  if they experience pain within 24–48 h.Participants were recalled after 24–48 h (2nd visit) and asked about their pain status and intake of prescribed medication. Radiographic examinations with intraoral radiograph revealed similar findings in the periapical region as in first visit. Those patients who reported not taking painkillers after the first visit were sent to the second investigator, who was blinded to the investigation for further assessment. The second investigator (SB) was blinded to randomization, did rubber dam isolation of the involved tooth and removed the temporary restoration and pulpal medicament. After access opening and complete removal of the pulp in pulp chamber with an Endo-Z bur , Access Opening (AO) visual analogue score was recorded.A #10K file was introduced in each canal of the mandibular molar, and participants were asked to rate their pain once more using Heft Parker VAS which was recorded as canal instrumentation or CI. Also, the bleeding score of each canal was recorded as bleeding score 2 or BS2. Ability to enter the pulp chamber and instrument the root canal without pain (VAS rating of 0) or mild pain   and comfIn this study, pain assessment before the application of pulpal medicament was recorded at three-time points: pre-operative (PO), post local anaesthetic administration (LA), caries excavation (EX) and at two-time points following the application of pulpal medicament (after 24–48 h): during complete access opening (AO), and canal instrumentation (CI).The bleeding score was recorded at two-time points: before applying pulpal medicament as bleeding score 1(BS1) and after applying pulpal medicament after 24–48 h as bleeding score 2 (BS2).Follow-up appointments were scheduled for all the patients after six months of completion of root canal therapy. Radiographic examinations of all treated patients in the first visit, second visit and six months after completion of root canal therapy were performed by investigator NS using the parallel technique. The following equipment was used: intraoral radiograph films , dental X-ray unit , Automatic Dental X-ray Film Processor . Assessment of periapical status was achieved by a consensus panel of two pre-calibrated experienced endodontists. Treatment was contemplated successful based on the following features: the absence of periodontal ligament widening, internal resorption, external resorption, furcation radiolucency, or periapical radiolucency.http://www.spss.co.in). The Shapiro Wilk test was used to check the normal distribution of quantitative data. The data was not normally distributed (p < 0.001) for all variables, so non-parametric tests were used. The qualitative parameters like bleeding were compared using the Chi-square test. The quantitative variables were compared using the Mann Whitney test between groups. The Wilcoxon sign rank test was used for the repeated measure of pain scores before and after the procedure. An alpha error was set to 5%, and a p-value of less than 0.05 was considered statistically significant.For statistical analysis, these data were scrutinized, coded, and entered into IBM SPSS statistics 24.0  were randomized . Age andp > 0.05). During postoperative complete access opening (AO) and canal instrumentation (CI), there was a significant decrease in the mean VAS score between Group C and Group D ( Group D .p < 0.05). Similarly, in group D, both AO and CI visual analogue scores have higher mean pain scores for first molar teeth than the second molar teeth. However, the difference was not statistically significant (p > 0.05).p − 0.243) and CI (p − 0.129) in group C. In Group D as well VAS = 0 during AO (0.288) and CI (0.141). In group C, before deroofing, mean VAS of 5.75 ± 10.64 and 17.50 ± 32.40 during the AO and CI procedure was recorded, respectively. In cases where partial deroofing was possible during AO, mean VAS of 7.87 mm ± 13.943 mm and 16.13 ± 22.25 during CI was recorded. There was no statistically significant result between before or partial deroofing in both groups.In p = 0.000). There was the presence of visible bleeding (96.9% of Group C patients and 96.4% of Group D patients) in the first visit (BS1). Post administration of pulpal medicament, there was a statistically significant reduction in bleeding from the pulp chamber in the second visit (BS2) in Group C,93.8% and Group D 89.3% had no bleeding (p = 0.533)  .The recall rate was 100% for patients. At 6-month recall, all patients who received pulpal medicament were clinically asymptomatic.Two experienced, independent investigators evaluated the postoperative periapical radiographs. Kappa values for inter-examiner agreement on outcome diagnosis using periapical radiography (PA) was 0.86–0.92 . All trePain perception and intervention effectiveness are influenced by various psychological factors . HyperalSeveral devices like Stabident, X tip, and Intraflow inject the local anesthetic solution into the cancellous bone adjacent to the tooth. However, these devices are technique sensitive and cause more discomfort to already stressed patients in inexperienced operators’ hands. These devices functioning depends mostly on locating and drilling the perforation sites, which might not be well accepted by patients. These devices are not only expensive but also have high maintenance costs. When not appropriately assembled, anesthetic solutions often leak from these devices .Alternative aesthetic solutions are available which are used for IANB for treatment of irreversible pulpitis. Mepivacaine, prilocaine and articaine are a few of such alternatives for lidocaine. However, a recent network meta-analysis revealed no difference in the efficacy of these alternatives, as mentioned above, when compared with lidocaine .The simplistic approach of using pulpal medicament overcomes the problems associated with the failure of IANB in irreversible pulpitis cases. Nevertheless, several case reports and review papers have assessed its effects, yet the findings were conflicting, contradicting and controversial . These pA standardized study protocol can aid in eliminating the confounding effects of intraoperative and postoperative variables on the use of pulpal medicaments . TherefoRandomization is a method of regulating and decreasing potential bias by maintaining an equilibrium of known and unidentified prognostic factors in the participants of the experimental groups while removing selection or allocation bias . BlindinThe present study utilized the Heft-Parker visual analogue scale. This visual analogue scale is a composite metric scale comprised of 6 category scale descriptors arranged unevenly on a horizontal line of 170-mm, offering patients several signals that may improve communication . PatientIn this present trial, a head-to-head comparison was made to illustrate the pulpal medicaments’ efficacy. Two pulpal medicaments used in this study to control pain and bleeding in severely hyperalgesia patients with symptomatic irreversible pulpitis were Caustinerf by Septodont  and D-Pulp by Ammdent. Both the pastes contain lidocaine and paraformaldehyde. However, the concentration of paraformaldehyde is more than twice in D-Pulp (460 mg in 1 gm) compared to Caustinerf (180 mg in 1 gm). Additionally, 1 gm of Caustinerf also contains two antiseptics: parachlorophenol (80 mg) and camphor(130 mg). The Caustinerf was clinically more effective than D-Pulp in reducing postoperative pain though statistically, there was no difference.The pulpal medicament is most effective in complete de-roofing cases . The reaThe pain score was slightly higher in the mandibular first molar than in the second molar. It could be because, in the Indian population, the most common root canal morphology encountered in the second mandibular is two mesial canals and one canal in the distal aspect . In contOn the contrary to postoperative pain, there was no significant difference in the bleeding status post-operatively in mandibular first and second molar as both the mandibular molars have similar average pulp volume . This stFrom the results obtained, both the groups showed a significant reduction in pain and bleeding status 24 to 48 h after placing a minuscule quantity of pulpal medicament. Caustinerf has less concentration of paraformaldehyde, and pain control was either equal or more than D-pulp, clinically. Therefore, clinicians can prefer the use of Caustinerf over D-pulp. It can be concluded from the above trial that judicious use of paraformaldehyde containing pulpal medicament can reduce pain and pulpal hyperaemia during a subsequent endodontic procedure, especially in mandibular molars with a clinical diagnosis of irreversible pulpitis with cold hyperalgesia. This short duration of pulpal medicament does not result in any radiographic periapical changes.The present investigation is, to our knowledge, the only double-blind, randomized trial of this intervention in severely symptomatic irreversible pulpitis. The relatively small sample size is a limitation of this study. Secondly, the use of devitalizes is considered for endodontic pain management protocol, and formaldehyde-based products are not in use in many countries. However, the present study suggests the use of it can be an alternative, painless method of achieving painless endodontic therapy. However, it cannot negate that any potential subsequent more extensive randomized controlled trials should use more patient-centred endpoints such as increased follow up periods and additional diagnostic aids like CBCT to evaluate any periapical changes.Within the limitations of the present study, it can be concluded that both medicaments (Caustinerf and D-Pulp) exhibit comparable effectiveness in postoperative pain reduction in the treatment of irreversible pulpitis in mandibular molars.10.7717/peerj.13397/supp-1Supplemental Information 1Click here for additional data file.10.7717/peerj.13397/supp-2Supplemental Information 2Click here for additional data file.


BackgroundFunctional gastrointestinal disorders (FGIDs) are syndromes identified based on a group of symptoms defined according to the criteria of the Rome Foundation. The most commonly observed disorders among the pediatric population are functional abdominal pain disorders and functional constipation. This study aims to identify the patterns of FGIDs among children in Makkah, Saudi Arabia.MethodsA retrospective cohort study was conducted at pediatric gastroenterology clinics from 2015 to 2019 in a tertiary centre in Makkah, Saudi Arabia. The FGID outcomes were compared with the patient's gender, age, and other characteristics using Statistical Package for the Social Sciences  software to analyze the data.ResultsOne hundred and fifty-two participants met the inclusion criteria, with a mean age of 5.49 ± 3.27 and an average weight of 20.68 ± 12.15 kg. Male patients account for 59.2% of the total population. The prevalence of abdominal pain was 17.84%, while constipation was 50.93%. There was a statistically significant association between abdominal pain and independent variables such as family history (p=0.004) and age, particularly in older children . A statistically significant correlation was found between constipation with gender (p=0.032) and family history (p<0.001).ConclusionThe prevalence of functional constipation and abdominal pain increased with age among children in Makkah City, with constipation being significantly more prevalent than functional abdominal pain. There is a significant relationship between age and family history with abdominal pain, whereas gender and family history are associated with a greater likelihood of constipation. Functional gastrointestinal disorders (FGIDs) refer to a group of conditions characterized by persistent, recurrent gastrointestinal symptoms with no identifiable organic etiology . The traThe pathophysiology of FGIDs is complex; nevertheless, several mechanisms are involved, including dysregulation of the brain-gut axis, dysbiosis, altered mucosal and immune functions, and visceral hypersensitivity ,5. AdditThe diagnosis of FGIDs is primarily clinical and based on the Rome IV criteria . Rome IVIn this study, we aim to evaluate the pattern, prevalence, and patient characteristics of functional constipation and abdominal pain among children attending the outpatient gastroenterology clinic at a tertiary hospital from 2015 to 2019 in Makkah, Saudi Arabia.A retrospective observational cohort study was conducted from 2015 to 2019 at pediatric gastroenterology outpatient clinics in a single tertiary centre in Makkah, Saudi Arabia. This study's main objective is to evaluate the pattern, prevalence, and patient characteristics among children diagnosed with FGIDs. Pediatric patients up to the age of 12 years were assessed for eligibility to participate in this study. Children meeting the Rome IV case definition criteria for FGIDs were analyzed and included in the study. Exclusion criteria include patients over the age of 12, those who did not meet the case definition for FGIDs, and those with incomplete data in their medical records. The Institutional Review Board at the Security Forces Hospital approved this study .Study tool and data collectionEligible patients' electronic medical records were reviewed and assessed for inclusion and exclusion criteria. Demographic data, clinical presentation, past family history of FGIDs and organic diseases, relevant laboratory tests, and imaging were collected and recorded in Excel-formatted data collection sheets. We compared the dependent variables of functional abdominal pain and constipation in children with concomitant characteristics, including gender, age, and family history.Statistical analysisAfter proper translation and coding, the data were entered into SPSS for analysis . The frequency of cases identified for each category and sub-category were expressed in numbers (n) and percentages (%) of the total sample. Then χ2 (Fisher’s exact) test was used to measure any association between cases and different categorical variables . Binomial logistic regression was conducted to χ2 (Fisher’s exact) test significant variables to identify the risk associated. The odds ratio and 95% confidence interval were obtained from regression analysis. P-values <0.05 were considered significant.The baseline characteristics of the patients are summarized in Table A total of 269 FGID patients visited the hospital during the 2015-2019 study period. Only patients who met ROME IV criteria were included in the study. Table There was a statistically significant association between abdominal pain and individual independent variables, including age category and family history. Table There was a statistically significant association between constipation and individual independent variables, including gender (p=0.032) and family history (p<0.001). Table Binomial regression analysis showed a statistical association between functional abdominal pain, age category, and the family history of patients. In addition to that, constipation was also found to be significantly associated with the gender and family history of the patients who participated in the study. Age group 5-12 years had a higher risk  of getting abdominal pain considering the 1-3 year age group as reference. Patients with an FGID family history had a 4.12-fold  increased risk of abdominal pain when compared to those without a family history. Compared to female patients, male patients had a higher chance of experiencing constipation . Patients who had a family history of FGID had a lower risk of getting constipation compared to others .Functional disorders such as abdominal pain and constipation are common health problems in children; in some countries, FGID problems affect one-third of children . EpidemiThe prevalence of abdominal pain increased linearly with age, increasing by approximately 6% per year . Twenty-One striking finding noted in our study was that male patients had a higher proportion of abdominal pain than female patients. This finding contradicts the results of a large meta-analysis that found a higher prevalence of functional abdominal pain disorders in female patients than in male patients 15.9% vs 11.5%) [.5% 11,1.Our study found that functional constipation was the most common FGID among the study population. This finding is consistent with other studies published in numerous regions worldwide ,17,18. TThe prevalence of FGIDs was significantly higher among the parents of children with FGIDs (64% vs 30.7%) compared to the parents of children without FGIDs, highlighting that FGIDs are genetically determined and influenced by environmental factors . In our Our present investigation had a few limitations. First, even though this study was conducted in a tertiary institution, a single institution may pose challenges regarding sample representation. Second, the retrospective design of this study makes it impossible to exclude recall bias. Third, some patients may have been missed because we are collecting data based on diagnosis codes.FGID is a common source of complaints among children and adolescents. Despite decades worth of clinical observation and research, it is still a challenging clinical entity with significant variations in its methodological approaches. According to the findings of this study, functional constipation was significantly more prevalent than functional abdominal pain among children in Makkah city. Furthermore, age and family history are significantly associated with functional abdominal pain, whereas gender and family history are significantly associated with functional constipation.


To assess whether persistent idiopathic dentoalveolar pain (PIDAP), a diagnosis of exclusion, exhibits common features that can facilitate its diagnosis. PIDAP is defined by the International Classification of Orofacial Pain (ICOP 6.3.) as ‘Persistent unilateral intraoral dentoalveolar pain, rarely occurring in multiple sites, with variable features but recurring daily for more than 2 h per day for more than 3 months, in the absence of any preceding causative event’.In this observational study, participants fulfilling the new ICOP diagnostic criteria of PIDAP were included, covering 16 years of consecutive data. A systematic, retrospective assessment of patients utilizing the new PIDAP criteria on complaints of chronic tooth pain in a referral‐based endodontic practice was undertaken. Non‐idiopathic cases were excluded on the basis of clinical and radiologic findings. A modified neuropathic pain questionnaire was used to describe the painful sensations. Furthermore, allodynia in the periodontal space and sensory changes in the oral mucosa were assessed using a periodontal probe.Amongst the 160 patients assessed, 78 (63 women) fulfilled the strict PIDAP criteria. Pain history of PIDAP included no nocturnal awakening (85%) and a ‘pulling/dragging’ pain quality (59%). In 69% of the patients with PIDAP, pain was associated with a root filled tooth at the same site. In 14% of the cases, no endodontic treatment was performed in the affected quadrant. Mechanical allodynia in the gingival sulcus was observed in 91% of patients with painful teeth or implants.In this observational study, PIDAP mainly affected females and was associated with undisturbed sleep and periodontal allodynia. Dental pain is a relatively common condition with a significant socioeconomic impact .The new International Classification of Orofacial Pain (ICOP) classification emphasizes the difference between neuropathic and idiopathic pain that can result in persistent dentoalveolar pain. The latter was the subject of this observational study. In this context, ‘Idiopathic’ is defined as ‘arising spontaneously or from an obscure or unknown cause’ , a trained endodontist and a physician with a focussed interest in pain, between January 2003 and June 2019. The use of this censored data for publication was approved by the local ethics commission . The majority of patients were referred from other endodontists within Germany because of ongoing pain after treatment , mucogingival lesions, internal or external resorption or possible lesions of endodontic origin resulted in the exclusion of the patient from the study group Table . PatientAll pain interviews and clinical examinations were conducted by the principal investigator. After their dental examinations reported here, the patients diagnosed with PIDAP were referred to headache and facial pain clinics or specialized pain therapists.The medical history was obtained using a health questionnaire that included questions pertaining to current health status Appendix  and the All patients completed a pain questionnaire for atypical or persistent tooth pain. This questionnaire Appendix  consisteThe area or tooth producing the most pain, as indicated by the patients, was recorded. All patients underwent the same intra‐ and extraoral examinations. Basic clinical examinations were performed as described in standard endodontic texts  using a periodontal probe  and applying light pressure. Patients were not asked before probing whether they had experienced any pain. Patients who had a reaction indicating that they might have felt pain were asked to state explicitly whether or not the touch was painful. The reaction was then compared with the corresponding reaction to the same procedure on the contralateral side. The original painful procedure was then repeated, and the patient was asked to comment on any differences compared with the non‐painful contralateral side. Probing of the gingival sulcus was performed in all quadrants.The periodontium was tested for bleeding on probing or pathological pocket depths (>3.5 mm) circumferentially. Patients presenting with one or more of these symptoms in the painful region were excluded from this study Figure . All teehttps://www.iasp‐pain.org/resources/terminology/) or as an unpleasant sensation (dysesthesia). If at least one of these symptoms was present, it was noted as a sensory change in the gingiva in the painful quadrant.The attached gingiva and mucosa in the painful quadrant were tested by touching them lightly with a periodontal probe and asking the patient for comparison to the contralateral side. The patient's reactions were also noted. No sensation, less sensation, painful sensations, or an unpleasant sensation in the painful quadrant compared with the contralateral side were classified as numbness, hypoesthesia or allodynia according to the IASP terminology (https://rstudio.com/products/rstudio/download/) were used to perform a descriptive statistical analysis. Normally distributed data sets (Shapiro–Wilk test) are presented as means and standard deviations, whilst non‐parametric data are presented as medians and ranges.The RStudio software tools  met the inclusion criteria for this study and were diagnosed with PIDAP. The site of pain was the teeth of 75 patients, implants in one patient or edentulous post‐extraction sites in two patients Table . The paiIn 25 cases in the PIDAP group, the persistent pain was preceded for more than 6 months by root canal treatments or other dental procedures that are listed to be relevant to a diagnosis of PTTNP in the ICOP classification, such as extractions, oral surgery, dental implants, orthognathic surgery and other invasive procedures. In 12 cases, persistent pain preceded the root canal treatment, and in 24 cases, no root canal treatment or other invasive dental procedures were performed on the tooth. In 12 cases, the root canal treatment preceded the beginning of persistent pain for less than 6 months, but since sensory changes were found in other quadrants as well, these cases met the criteria for PIDAP, not PTTNP Appendix . Cases iOther chronic pain conditions reported by patients with PIDAP included chronic back pain , irritable bowel syndrome (3), migraine (4), fibromyalgia (2) and tension headache (1). A history of depression was reported in nine cases and psychosis in one. The most frequently reported medical conditions were thyroid disorders (21), including 12 cases of Hashimoto's thyroiditis. Eleven patients had cardiovascular and respiratory disorders. Other disorders or diseases were present in very small numbers of patients. Twenty‐one patients reported no other health problems besides the existing persistent intraoral pain.Drugs taken on a regular basis included l‐thyroxin (18), contraceptive medication (4), drugs used for chronic pain treatment (8), psychotropic drugs (3) and cardiovascular drugs (10).The pain had been present for an average period of 2.7 years before the examination . A group of 17 women had pain persisting for more than or equal to five years. The maximum pain intensity during the 2 weeks prior to assessment ranged from 2 to 10 on the NRS‐11 scale . The mean average pain score in the same period was 3.8 (median: 3), and the mean NRS‐11 scores for female and male patients were 3.8 and 4.1, respectively.Sixty‐six of the 78 (85%) patients stated that the pain did not wake them at night. Furthermore, 64 (82%) patients experienced pain‐free intervals on waking in the morning before the pain set in. Pain was present during the daytime for more than 2 h in all patients.Patients generally used more than one term to describe the nature of their pain. The most frequently used adjectives were as follows: ‘pulling/dragging’, reported by 46 of 78 patients (59%); ‘pressing’ by 41 (52%); ‘burning’ by 33 (42%); ‘tingling’ by seven (9%); ‘electric’ by three (4%); and ‘stabbing’ by 14 (18%). Forty‐three (55%) patients reported experiencing pulsating or throbbing pain at the affected site from time to time. When describing the quality of their pain in more words, patients frequently used non‐standard, figurative expressions that differed from more common ways of describing toothaches, such as ‘like being stabbed with a knife’, ‘like a wound’, ‘like dead tissue that is nevertheless painful’, ‘as if the tooth were to explode’ and ‘as if the bones were moving’.Pressure to the periapical bone exerted by digital palpation was never painful, nor could pain be elicited by vertical tapping on a tooth with an instrument in any case. Discomfort was elicited by horizontal tapping in six patients. Mechanical allodynia of the gingival sulcus was found in 68 of 75 teeth and in one implant. Thus, allodynia in the periodontium/peri‐implant mucosa was observed in 69 of 76 patients with painful teeth or implants (91%). In two of the cases in which the pain affected the edentulous region, this sign could not be tested. The painful section invariably consisted of only part of the gingival sulcus and never included its entire circumference. The same symptoms could frequently be elicited in the sulcus of the adjacent teeth or in the antagonistic or contralateral quadrants. An allodynic area in the gingival sulcus of the neighbouring teeth was present in 53 cases. More than one quadrant was affected in 39 cases: two quadrants in 22 cases, three quadrants in 11 cases and all four quadrants in six cases.The gingiva and mucosa of all patients were checked for sensitivity changes to touch by using the tip of a periodontal probe to slightly touch the gingiva and mucosa in the painful quadrant, first on the non‐painful contralateral side and then on the affected painful side. In 9 cases, patients reported numbness near the site of the pain after repeated comparisons with the non‐painful contralateral side. None of the patients had been aware of this numbness before the examination. Twenty‐eight patients showed sensitivity changes other than numbness in the painful quadrant beyond the gingival sulcus; mechanical allodynia was present in five patients. Seven patients reported reduced sensitivity to touch (hypoesthesia) and 15 reported discomfort when touched with a periodontal probe compared to the non‐painful side. In seven patients, more than one sensitivity change in the fixed gingiva was present concurrently.The painful sensation sometimes increased as a result of the examination, especially on contact with the gingival sulcus. A total of 32 patients reported an increase in pain levels after completion of the examination.In this observational study, strict PIDAP criteria were applied to illuminate the condition from the dentist's perspective. This allowed the identification of PIDAP features that have not been described previously, including the absence of nocturnal pain and the presence of allodynia in otherwise healthy periodontal sites.Until recently, the nomenclature for the conditions under investigation was not standardized , chronic pain conditions (23%), and depression (10%) were reported by the patients. Because this information was questionnaire‐based, its completeness and accuracy were not assured. It was only included to describe the group of patients under investigation in more general terms. Nevertheless, the relatively high frequency of thyroid disorders in this cohort warrants further research. An examination of a large sample of self‐reported chronic pain   has also been described in neuropathic pain. In this regard, mechanisms similar to those of ‘wind‐up’, a progressive, frequency‐dependent increase in excitability, may play a role   had this sensory abnormality, often not only in the painful tooth but also in other teeth and quadrants. Neurophysiological research on this topic has shown that trauma to one dental nerve may alter the processing of pain in neighbouring teeth and other quadrants  and to identify characteristics of specific groups that may be due to changes in the pain processing system typical of PIDAP.Nevertheless, this observational study was limited by the fact that it was not a cross‐sectional study, and the pain and treatment history depended on the patient's memory. As a result, no conclusions can be drawn regarding the prevalence of the conditions under investigation. Furthermore, there was a selection bias because patients were mostly seen in endodontic clinics Figure , which rThe focus of the current work was on how PIDAP patients presented in endodontic practice, and which were the key features of their condition from a dental perspective. In a future study, an attempt will be made to follow the PIDAP patients identified here to assess how their pain was managed.PIDAP is normally a diagnosis of exclusion, but common features may exist;No nocturnal awakening due to pain was reported by most patients with PIDAP;The sulcus around the affected tooth/implant was painful upon light touch of the periodontal probe in a significant proportion of PIDAP patients;PIDAP mainly affected females;The five most frequent pain descriptors were ‘pulling/dragging’ (59%), ‘pulsating’ or ‘throbbing’ (55%), ‘pressing’ (52%) and ‘burning’ (42%).Persistent idiopathic dentoalveolar pain is mainly diagnosed by exclusion. For clinicians, the typical features of PIDAP can help to better differentiate this type of pain from odontogenic and other possible pain conditions. The identification of allodynia in the gingival sulcus of affected teeth/implants appears to be a common PIDAP feature easily detected by the dentist, as is the information that the pain does not wake the patient at night. In view of the rarity of PIDAP, special networks or centres are needed to generate a sufficient number of cases whose evaluation can provide the basis for an improvement in the diagnosis and treatment of patients with persistent toothaches.The use of data pertaining to this observational study was approved by the local ethics committee .The authors have stated explicitly that there are no conflicts of interest in connection with this article.Appendix S1Click here for additional data file.Appendix S2Click here for additional data file.Appendix S3Click here for additional data file.


Urolithiasis causes severe acute pain and is commonly treated with opioid analgesics in the emergency department (ED). We examined opioid analgesic use after episodes of acute pain.Using data from a longitudinal trial of ED patients with urolithiasis, we constructed multivariable models to estimate the adjusted probability of opioid analgesic use 3, 7, 30, and 90 days after ED discharge. We used multiple imputation to account for missing data and weighting to account for the propensity to be prescribed an opioid analgesic at ED discharge. We used weighted multivariable regression to compare longitudinal opioid analgesic use for those prescribed vs not prescribed an opioid analgesic at discharge, stratified by reported pain at ED discharge.Among 892 adult ED patients with urolithiasis, 79% were prescribed an opioid analgesic at ED discharge. Regardless of reporting pain at ED discharge, those who were prescribed an opioid analgesic were significantly more likely to report using it one, three, and seven days after the visit in weighted multivariable analysis. Among those who were not prescribed an opioid analgesic, an estimated 21% (not reporting pain at ED discharge) and 30% (reporting pain at discharge) reported opioid analgesic use at day three. Among those prescribed an opioid analgesic, 49% (no pain at discharge) and 52% (with pain at discharge) reported using an opioid analgesic at day three.Urolithiasis patients who received an opioid analgesic at ED discharge were more likely to continue using an opioid analgesic than those who did not receive a prescription at the initial visit, despite the time-limited nature of urolithiasis. Urolithiasis is an acute painful condition with increasing prevalence globally.15Overall opioid prescribing in the United States has decreased since 2012 as efforts have been underway to limit access to these medications in response to the opioid epidemic.Our objective was to determine whether ED patients with urolithiasis, a time-limited, acute pain condition, who were discharged with an opioid analgesic prescription were more likely to report opioid analgesic use after the ED visit than patients who did not receive a prescription at the end of the ED visit. We specifically aimed to compare prescription opioid analgesic use after the ED visit according to two groups of patients: those who were still in pain at the time of ED discharge vs those who were no longer reporting pain. Using existing data from a randomized controlled trial,We analyzed data collected as part of a parent randomized controlled trial  that was initially designed to compare diagnostic techniques for urolithiasis.What do we already know about this issue?Over the past decade opioid analgesic prescribing has declined in the US overall, but prescribing for urolithiasis, a severe acute pain, has been slow to decrease.What was the research question?Does an opioid analgesic prescription at ED discharge affect continued use after an ED visit for urolithiasis?What was the major finding of the study?Urolithiasis patients discharged with a prescription were 1.8 to 3.6 times more likely be using opioids at 3 and 7 days than those discharged without an opioid prescription.How does this improve population health?Although urolithiasis is acute and expected to resolve quickly, further limiting prescription of opioid analgesics might prevent their prolonged use after urolithiasis.The parent trial enrolled 2,759 adult ED patients with suspected urolithiasis  for whom treating physicians ordered diagnostic imaging. The parent trial invited ED patients with suspected urolithiasis who were between 18–75 years of age, not pregnant or obese, and had no history of nephrectomy, renal transplant, or dialysis to participate in the study.For our primary analysis, we defined four cohorts based on two exposure variables at the time of ED discharge: receipt of an opioid analgesic prescription ; and pain . The four cohorts were as follows: 1) reported no pain at ED discharge and did not receive an opioid analgesic prescription; 2) reported pain at discharge but did not receive an opioid analgesic prescription; 3) reported no pain at discharge but received an opioid analgesic prescription; and 4) reported pain and received an opioid analgesic prescription at discharge.At each follow-up , trained research coordinators asked participants whether they were currently taking an opioid analgesic to treat the pain due to the original condition that brought them to the ED when they enrolled in the trial.We described characteristics of the study sample, providing the count and percentage for categorical variables and median and interquartile range IQR) for continuous variables. Because receipt of an opioid analgesic prescription at ED discharge was not randomly assigned, we enacted statistical measures to reduce confounding by factors that might have influenced which patients received opioid analgesic prescriptions. Using the population of patients with suspected urolithiasis , we used inverse propensity score weightingFor this adjustment we estimated the conditional probability of receiving an opioid prescription at ED discharge, given covariates previously identified to predict that probability in this population: urolithiasis diagnosis; gender; age; education level; race/ethnicity; self-rated health; health insurance status; pain level at ED arrival; duration of pain prior to arrival; calendar time; and presence of a prescription drug monitoring program (PDMP) in the state at the time of the visit.Next, we imputed values to substitute for missing data on opioid analgesic use at follow-ups with chained equations31In the multiple imputed data sets, we first focused on the subpopulation of urolithiasis-diagnosed participants not missing reported pain at ED discharge (n = 892). In this subpopulation we used generalized estimating equations to account for within-subject correlation due to repeated follow-ups, and we constructed multivariable generalized linear models with a logit link to estimate the odds of using an opioid analgesic at follow-up for each of the four cohorts. We created a dummy variable to index each follow-up to capture any non-linear pattern of using an opioid analgesic after ED discharge and allowed the responses to change over time for participants who were prescribed vs not prescribed an opioid analgesic at discharge by including an applicable interaction term. The inverse probability weights were then used to adjust for factors that influenced which patients received an opioid analgesic prescription at ED discharge.This final model produced estimated odds ratios (OR) of using an opioid analgesic at each follow-up visit comparing those with and without an opioid analgesic prescription at ED discharge, stratified by whether or not the participant reported any pain at the end of the ED visit. Additionally, for each of these four cohorts, stratified by opioid analgesic prescription and overall we used the multivariable model to estimate the adjusted percentage with a 95% confidence interval (CI) of participants who reported using an opioid analgesic at each follow-up.In a sensitivity analysis, we repeated the analysis in the larger subpopulation of participants with suspected urolithiasis and complete data on pain at ED discharge .Of the 2,759 participants enrolled in the STONE trial, we excluded 12.5% (n = 346) who were admitted to the hospital, had a cancer or psychiatric diagnosis, or were missing baseline characteristics . Of the In multivariable analysis using inverse probability weighting to adjust for the probability of receiving an opioid analgesic prescription at ED discharge, there were significant differences in opioid analgesic use at follow-up between cohorts. Regardless of whether participants had pain at the end of the ED visit, those who were prescribed an opioid analgesic were more likely to report using one, three and seven days after the visit . For exanot prescribed an opioid at discharge, an estimated 21% of those with no pain and 30% of those with pain reported using an opioid analgesic at the three-day follow-up interview. In contrast, for the cohorts that were prescribed an opioid analgesic, 49% of those not reporting pain at discharge and 52% of those in pain at discharge reported using an opioid analgesic 3 days after the visit  of those receiving an opioid analgesic prescription at discharge reported using an opioid seven days after the visit, while only 18.0% (12.0–26.1%) of those without an opioid analgesic prescription at ED discharge reported using one. At day 30 and day 90, the difference between groups was not statistically significant. Overall, in the total population of acute renal colic patients in this study, an estimated 12.5% (9.4–16.4%) reported using an opioid analgesic to treat that pain 30 days later, and 4.3% (2.6–7.1%) were still doing so 90 days after the initial ED visit.In the sensitivity analysis including the larger population of participants with suspected urolithiasis, the association between receiving an opioid analgesic prescription at ED discharge and using that prescription was slightly stronger for both those reporting pain at the time of ED discharge and no longer experiencing pain, especially at day 3 . AppendiThirty days after an ED visit for urolithiasis, 7–17% of patients in our study sample reported using an opioid analgesic to treat the pain that prompted their visit . If presIn our sensitivity analysis including all participants with suspected urolithiasis, we observed similar trends , but morOur study is not the first to find ongoing opioid analgesic use after acute pain more likely for patients prescribed an opioid analgesic. In one study of ED patients with a broad array of acute painful complaints, 17% of patients who filled their opioid analgesic prescription continued receiving it one year later.34A recent retrospective study shared a similar concern for patients with acute urolithiasis.This analysis is subject to several limitations. As with all longitudinal studies, this investigation had missing data on reported pain at ED discharge and opioid analgesic use at follow-ups. A smaller number of baseline characteristic data was missing; however, excluding this small portion of participants (3.3%) should not meaningfully have changed our results. Unfortunately, nearly one third of the sample was missing reported pain at ED discharge. We believe that pain at the end of the visit was important information needed to answer the research question about whether participants who receive an opioid analgesic prescription at discharge were more likely to continue using an opioid analgesic after the visit, and that 892 participants was sufficient to build our multivariable models. The point when patients were leaving the ED proved to be a difficult time for study staff to obtain information from patients, so missingness at this time point might not be related to the exposure or outcome in this study. We chose to omit those participants without pain data at ED discharge from this analysis and not attempt to impute reported pain at discharge in addition to our outcome.One quarter of follow-up observations were missing reported opioid analgesic use, the outcome for this analysis. Omitting this missing information could result in biased estimates, as this data was not missing completely at random. To overcome that limitation, rather than assume the missing data was similar to that observed, we elected to use multiple imputation with chained equations to fill in values for those missing observations,31Another potential limitation of this study is that overall opioid analgesic prescribing has changed since the data was collected in 2011–2013. However, opioid analgesic prescribing for acute painful conditions such as urolithiasis has decreased very slowly compared to overall prescribing.Finally, the parent study did not collect information on exposure to opioid analgesics prior to the ED visit, opioid use disorder, or existing chronic pain or mental health conditions. These factors could have influenced both physician prescribing and opioid analgesic use at follow-up, and thus could have affected our results. Cotta et al were able to control for an existing prescription and still found that patients who received an opioid analgesic prescription at the initial visit for urolithiasis were more likely to refill a prescription than those not receiving a prescription at the initial visit.32It is not well established whether having opioid use disorder means a patient is more, perhaps due to requesting the medication, or less, if the physician is aware of the patient history, likely to receive an opioid analgesic prescription. The parent study also did not track how many pills of opioid analgesics were prescribed or refills received, which would both be confounding variables. Related to refills, it is not known whether participants who reported using an opioid analgesic 90 days after the initial ED visit received a refill, a new prescription, or were using remaining pills from the original prescription.In this secondary analysis of a longitudinal study of acute urolithiasis ED patients, one eighth of our sample reported using an opioid analgesic 30 days after the visit. We found that those prescribed an opioid analgesic at ED discharge were more likely to report using opioid analgesics a week after the visit than those who did not receive an opioid prescription. Of great importance, opioid analgesic use continued for those who had reported that their pain was relieved at the end of the ED visit. The most current practice guidelines for managing pain due to urolithiasis suggest reserving opioid analgesics as a last resort. Yet opioid analgesics are still often prescribed for urolithiasis, and our study findings show they are prescribed at ED discharge even when a patient’s pain has resolved by the end of the visit. Especially given evidence that NSAIDs are more effective at pain reduction for urolithiasis, further limiting prescription of opioid analgesics at ED discharge might prevent their prolonged use.


Several factors such as neck pain intensity, disability, anxiety, depression, female sex, or a previous history of headache are associated with post-whiplash headache. However, the possible role of psychosocial factors contributing to the presence of headache or worsening of headache after a whiplash trauma remains unclear. To address this gap in knowledge, there is the need to assess psychosocial factors concerning headache shortly after a whiplash injury.To evaluate psychological features, pain and disability in people with acute whiplash associated disorders (WAD) and compare these features between those with and without headache.Case-control study.A secondary care traumatology center.Forty-seven people with acute WAD were recruited; 28 with headache, and 19 without. All participants completed self-reported questionnaires including Visual Analogue Scale (VAS) for neck pain intensity, the Neck Disability Index (NDI), Pain Catastrophizing Scale (PCS), Tampa Scale Kinesiophobia-11 (TSK-11), and State-Trait Anxiety Inventory.P < .001), neck disability (P < 0.001), pain catastrophizing (P < .001), kinesiophobia (P < .001), and anxiety state (P = .007) and trait (P = .05) were higher in those with headache when compared to those without. In addition, high levels of neck pain (P = .025), moderate levels of neck disability (P < .001), moderate levels of pain catastrophizing (P = .015), and moderate (P = .002) and severe (P = .016) levels of kinesiophobia were related to the presence of headache.Neck pain intensity (The level of neck pain intensity and disability, kinesiophobia, catastrophizing, and anxiety were all greater in people with acute WAD who presented with a headache compared to those without headache. A whiplash injury is defined as the acceleration-deceleration mechanism that produces a transfer of energy to the neck, usually provoked by a rear-end car collision, which can lead to a variety of symptoms and clinical manifestations, known as whiplash associated disorders (WAD) , 2. WhipAccording to the International Headache Society (IHS), “headache attributed to whiplash” is a headache that appears within 7 days after the accident, or a previous headache that worsens in this period of time after the accident . Indeed,Several factors such as neck pain intensity, disability, anxiety, depression, female sex, or a previous history of headache are associated with post-whiplash headache . HoweverA case-control study was carried out involving patients with acute pain attributed to a whiplash injury due to a traffic accident who were attending the Clinica San Vicente, Madrid, Spain, from September 2020 to February 2021. Ethical approval was granted by the applicable institutional human research ethics committee from University Rey Juan Carlos, Madrid, Spain (Ref: 1003202108121). All participants gave their written informed consent to participate in this study. The study was conducted according to the Declaration of Helsinki and is reported in accordance with STROBE guidelines Consecutive patients with a diagnosis of WAD were recruited from the Traumatology Department of the Clinic. By the nature of the Traumatology Clinic, we only collected victims of the accidents. After being diagnosed by a physician, who informed patients about the study, those who agreed to participate provided written informed consent and were referred to the Physiotherapy Department.Inclusion criteria consisted of Grade II WAD, as defined by The Quebec Task Force on Whiplash-Associated Disorders , 2 betweThe sample size estimation was performed using the Grammo calculator v.7.12. Based on the analysis of variance of means and estimating an alpha risk of 5% (0.05), a beta risk of 20% (0.20), a unilateral contrast, a typical deviation of 10% (0.10), a minimum clinical difference of 20% (0.2) in Neck Disability Index in neck pain disorders ; good construct validity when compared to Global Rating of Change (P < .001)) and is commonly used to assess disability in people with WAD [with WAD .Tampa Scale Kinesiophobia-11 (TSK-11). The Spanish version of the TSK-11 was used to measure fear of movement . This tool is composed of 11 items and scores range from 1 (strongly disagree) to 4 (completely agree). The total score can range from 11 to 44, with higher scores reflecting greater kinesiophobia. The TSK-11 has good test-retest reliability (ICC (95% CI) 0.81 (0.71 to 0.88)) and a highly significant correlation with change scores on the TSK  [ < .001) , 19.Pain Catastrophizing Scale (PCS). The Spanish version of the PCS was used  [ = 0.84) . This sc = 0.84) The State-Trait Anxiety Inventory. The Spanish version of this questionnaire  was used to assess anxiety; good construct validity since negative correlation was found with Short Form Health Survey-12 mental health (rho=−0.6752) [−0.6752) . This qut-test was applied for paired variables when the data had a parametric distribution. The Mann-Whitney U test was used to analyze data with a non-parametric distribution. The χ2 test was used to compared qualitative variables. Independent variables were age, sex, height, weight, and days from the accident to evaluation. The correlation of variables was performed through odds ratio; dependent variables were classified as mild, moderate and severe: VAS , NDI , TSK-11 , PCS , Anxiety State and Trait . The confidence level used was 95% (0.05), and the power of the study was 90% (0.1).The statistical analysis was carried out using IBM-SPSS Statistics 24 software. The Kolmogorov-Smirnov test was applied to test the distribution of the data. Student’s Forty-nine people were recruited and, after the exclusion of two, 47 patients remained and participated in the study . Among tP < .01) and Trait (P = .05) , NDI, TSK-11, PCS, and Anxiety State  .We also performed both type of analyses by excluding those patients from headache group who presented a previous headache condition (n = 5). This, however, did not influence the results.This is the first study to assess differences in psychological features, neck pain intensity and disability between patients with acute WAD grade II presenting either with or without headache. Our findings demonstrate that the level of neck pain and disability, kinesiophobia, and catastrophizing are greater in those patients with WAD who have headache.It has been reported that headache can occur in up to 60% of people shortly after a whiplash injury [The influence of psychosocial factors on symptoms in people with WAD has been frequently evaluated , 25 and Unique to the current study, we found that the presence of high levels of neck pain, moderate levels of neck disability and pain catastrophizing, and moderate/severe levels of kinesiophobia were associated with the presence of headache. Psychological features can be evident in many patients with WAD and, according to our results, especially in those with headache. Since treatments addressing these factors have shown promising results , and psyIt is relevant to note that the participants completed the questionnaires at the Traumatology Clinic which is where they were going to be evaluated for possible economic compensation; although they were advised that the information collected in our study was not related to their legal case and would not be used, this still may have influenced their answers. Additionally, this study only evaluated pain intensity, disability, psychological factors, and headache status in the short term. Future studies should address the interaction between all these factors and long-term health status.A further consideration is the sample size and a larger sample size may have resulted in the trend observed for anxiety to become a significant result. Previous work has shown that anxiety is among several psychological variables which strongly predict the transition from acute to chronic pain , 35 as wMoreover, although our exclusion criteria were developed to avoid the inclusion of patients with concussion, this condition is highly variable in its presentation and usually very similar to whiplash symptomatology. Therefore, some patients with mild concussion could be included in our sample .Finally, we did not collect data regarding TMD symptomatology, which can be common in people who have sustained a whiplash injuries and for people with headache , 39.The level of neck pain intensity and disability, kinesiophobia, catastrophizing, and anxiety were all greater in people with acute WAD grade II who presented with a headache compared to those without headache. People with headache were eight times more likely to have severe neck pain, more than 34 times more likely to have at least moderate neck disability, 10 times more likely to have moderate levels of catastrophizing and more than 10 times more likely to have moderate or severe levels of kinesiophobia. Further research is encouraged to determine whether the presence and extent of headache influences longer term outcome.Ethical approval was granted by the applicable institutional human research ethics committee from University Rey Juan Carlos, Madrid, Spain (Ref: 1003202108121).E.A.L. was the lead researcher, formulated the focus of the study and conducted the study. C.B.U. performed the statistical analysis. J.M.O. contributed to manuscript development. D.F. contributed to the formulation of the study and the development of the study. C.R.B. was the director of the study and contributed to statistical analysis. E.A.L. drafted the manuscript, and C.B.U., J.O.M., D.F., and C.R.B. revised the manuscript. All authors approved the final version of the manuscript.pnac038_Supplementary_DataClick here for additional data file.