Objective. This study aimed to evaluate the efficacy and safety of PRF for treating PHN involving the ophthalmic branch of the trigeminal ganglion. Study Design. An observational study. Setting. All patients received PRF of the ophthalmic branch of the trigeminal nerve, pain intensity was assessed by a visual analogue scale (VAS), and complications before and after PRF stimulation were noted. Methods. Thirty-two patients with PHN of the ophthalmic branch were treated by PRF of the ophthalmic branch with controlled temperature at 42°C for 8 min. Pain relief, corneal reflex, sleep quality, and satisfaction were assessed for all patients. Results. Thirty out of 32 patients (93.75%) reported significant pain reduction after PRF treatment. Twenty-eight of them (87.5%) were satisfied with their sleep and obtained a pain score lower than 3 following the procedure. Only two patients had a recurrence of the severe burning pain and returned to the hospital for other medical therapies 2 weeks after the PRF procedure. No patient lost the corneal reflex. Limitations. This study is an observational study and a nonprospective trial with a short-term follow-up period. Conclusion. PRF of the trigeminal ganglion of the ophthalmic branch can significantly reduce pain sensation and improve sleep quality and satisfaction for PHN of the ophthalmic branch.Postherpetic neuralgia (PHN) is a painful, long-lasting condition as a consequence of nerve damage resulting from a herpes zoster infection. Although there are many different treatments available to reduce pain duration and severity, PHN is often refractory to them and no single therapy shows an effective cure for all cases of PHN, especially for those involving the ophthalmic branch of the trigeminal nerve. Pulsed radiofrequency (PRF) is a minimally invasive procedure for pain treatment that has been practiced over the past decade. However, its clinical efficacy and safety for treating PHN involving the ophthalmic branch of the trigeminal nerve have not been evaluated.  People infected with the varicella-zoster virus are at risk of developing herpes zoster. Although most cases resolve spontaneously, the pain associated with herpes zoster does not resolve in a substantial number of patients, resulting in a chronic pain condition called postherpetic neuralgia (PHN). PHN is the most common complication of zoster infection and remains a challenging condition to treat. It has been reported that an estimated 12.5% of patients with zoster infection aged ≥50 years develop PHN three months after zoster infection onset and the proportion affected increases sharply with age . Of the Medication, nerve blocks, and chemical neurolytic blocks have been used to treat PHN of the ophthalmic branch. Unfortunately, the effects are limited and often produce intolerable side effects. In recent years, spinal cord stimulation has been found to be a useful technique for the treatment of intractable chronic neuropathic pain ; howeverForty-eight patients with PHN of the ophthalmic branch were recruited between August 2014 and February 2017 from the Department of Pain Management, the Second Affiliated Hospital of Guangzhou Medical University. Inclusion criteria were diagnosis of classic PHN of the ophthalmic branch. Patients experienced lancinating or burning pain, paresthesia, or pruritus for over three months. All patients reported moderate to most intense pain (>5) on a visual analogue score (VAS), ranging from 0 (no pain) to 10 (the most intense pain). Ten patients had facial numbness, decreased corneal reflex, or visual impairment on the symptomatic side. Anticonvulsants such as pregabalin 75 mg q12 h were used to treat lancinating pain, while tramadol 100 mg q12 h and a tricyclic antidepressant drug amitriptyline 12.5 mg qn were prescribed for easing burning pain. Patients were excluded from the study if they fulfilled one of the following criteria: noncompliance with physician's advice, infection on the skin or the deep tissue at the puncture site, the presence of bleeding tendencies, or receiving anticoagulant therapy which could not be replaced with intravenous low-molecular-weight heparin subcutaneous injection. In addition, patients with unstable, severe cardiovascular or cerebrovascular disease, such as trigeminal neuralgia secondary to cranial tumors, were also excluded. Sixteen patients were excluded based on these criteria. This study was approved by the Institute Review Board of the Second Affiliated Hospital of Guangzhou Medical University. Informed consent for participation in this study was obtained from the patients before the treatment.μg/kg i.v was administered by bolus. Following sterile prep and drape, the C-arm was positioned 15–25 degrees ipsilaterally and 30–35 degrees caudally to show the foramen ovale, located at the upper third of the mandibular ramus, inside of the condyle  was divided into the following four grades, the number of patients in each grade was counted: grade1, pain score less than 2; grade 2, pain score 3 or more on the VAS scale; grade 3, pain score 6 or more on the VAS scale; grade 4: complete relief. The number of patients in each grade was counted separately.Sleep quality was divided into the following five levels evaluated by the patients themselves: 1, good sleep; 2, relatively satisfied sleep; 3, sleep after medicine; 4, poor sleep; 5, cannot sleep. The number of patients with different sleep quality levels was counted before and 1 month after PRF.The patient's treatment satisfaction was divided into the following five grades: 1, strongly dissatisfied; 2, somewhat dissatisfied; 3, neutral; 4, somewhat satisfied; 5, very satisfied.p value < 0.05 was deemed statistically significant and p value < 0.001 was deemed statistically very significant.Statistical analyses were performed using Prism 5.0 software. The immediate postoperative VAS was analyzed using the chi-square test. We used a linear mixed model with a Toeplitz covariance structure  for the analysis of repeated measures structure; an analysis of the primary and secondary endpoints of the full analysis set, which contained unbalanced data, was conducted. A After 16 patients were excluded based on the exclusion criteria, data from 32 patients with PHN of the ophthalmic branch  were analyzed in the study. The duration of disease ranged from 0.5 years to 3 years, with an average of 1.5 ± 0.75 years. The patients' detailed information is shown in Pain was efficiently reduced in all patients after the PRF during follow-up. The number of patients in grade 3 pain relief increased gradually to 30 after three months, while the number in grade 4 was 8 in the first week and dropped to 0 at the end of follow-up , Table 2For all patients, sleep quality significantly improved after the PRF procedure, in which 87.5% (28 of 32 patients) were satisfied with their sleep and obtained a pain score lower than 3 following the procedure .Twenty-eight patients (68.75%) were satisfied after the PRF treatment during the follow-up period .Following PRF of the ophthalmic branch of the trigeminal ganglion, intolerable pain, sleep quality, and quality of life were significantly improved in nearly all PHN patients. PHN is a classic neuropathic pain that presents as lancinating and burning pain and is associated with paresthesia. The paresthesia can be expressed as allodynia and hyperalgesia , where tStudies have shown that mortality and severity of PHN are closely related to the patient's age, the severity of the rash, prodromal pain symptom, and gender . The incNerve stimulation is another method to control neuropathic pain via both central and peripheral pathways , 24–26; Thermal radiofrequency has been used for treating trigeminal neuralgia for decades and the ophthalmic branch was not a contraindication . PreviouPrevious research showed that PRF delivered at 42°C on the rat dorsal root ganglion will not induce structural changes aside from transient endoneurial edema and collagen deposition . More reIn summary, PRF of the trigeminal ganglion of the ophthalmic branch can significantly reduce pain sensation and improve sleep quality and the quality of life; therefore, it may be a candidate for PHN of the ophthalmic branch.


NICE guidelines and Maudsley prescribing guidelines both stipulate that patients over the age of 65 prescribed lithium or antipsychotic medication should have their bloods and physical parameters monitored regularly. There is currently no provision from the community mental health teams in Edinburgh to provide this monitoring, which falls to the patients GP. Following an initial data collection, it was found that there was no monitoring advice being provided on immediate discharge letters (IDLs) for patients discharged from two functional old age psychiatry inpatient wards at the Royal Edinburgh Hospital. This patient group often have comorbid medical conditions and therefore monitoring of their psychotropic medication is especially important. The aim of the QI project was for 100% of patients discharged from thesewards on lithium or antipsychotic medication to have appropriate advice documented on their immediate discharge letter (IDL) with regards to medication monitoring.Data were collected monthly by reviewing the notes of all discharged patients to determine the frequency at which medication monitoring advice was documented on IDLs from the two wards. A proposed new template for discharge letters which included advice on medication monitoring was discussed and agreed with the old age psychiatry team in Edinburgh. This was disseminated to the appropriate medical staff members and was included in induction packs for junior doctors. Following this a new “canned text” template was implemented to automatically populate the discharge letter with advice depending on whether they were antipsychotics/lithium/neither.IDLs for 91 patients discharged between May 2020 and February 2021 were reviewed. Baseline data showed that 0% of patients (n = 15) had appropriate monitoring advice documented on their IDL. Following initial introduction of monitoring advice to the induction pack for junior doctors, the mean frequency of completed advice on IDLs was 50.9% across 6 months. Following implementation of the canned text, the frequency of completed advice on discharge letters for February 2021 was 100% (n = 7).This QI project has been successful in improving the rate of appropriate advice for antipsychotic and lithium monitoring being provided on immediate discharge letters. It is hoped that this will help reduce adverse effects associated with antipsychotics and lithium in older psychiatric patients. Further work could be done on determining the frequency that the advised monitoring is being carried out.


Guidelines recommend that GPs give patients lifestyle advice to manage hypertension and diabetes. Increasing evidence shows that this is an effective and practical treatment for these conditions, but it is unclear whether GPs offer this support.To investigate trends in the percentage of patients with hypertension/diabetes receiving lifestyle advice versus medication.This was a trend analysis of self-reported data from the annual Health Survey for England (HSE) (2003–2017) and GP-recorded data from the QResearch database (2002–2016).The percentage of patients with hypertension or diabetes who received lifestyle advice or medication was calculated in each year. Associations between likelihood of receiving lifestyle advice and characteristics were assessed using multivariable logistic regression.trendP<0.001; QResearch 11.0% to 22.7%; trendP<0.001). For diabetes, there was a non-significant decline in self-reported receipt of lifestyle advice  and a significant increase in medically recorded delivery of this advice . Patients with hypertension who were overweight or obese were more likely to receive lifestyle advice than those of a healthy weight, whereas the opposite was true for diabetes.The percentage of patients receiving lifestyle advice was consistently lower than those receiving medication in both self-reported and medical records. There was consistent evidence of increasing trends in the percentage of patients with hypertension receiving lifestyle advice (HSE 13.8% to 20.1%; Only a minority of patients with diabetes or hypertension report receiving lifestyle advice or have this recorded in their medical records. Interventions beyond guidelines are needed to increase the delivery of behavioural interventions to treat these conditions. For example, it is possible that patients may forget advice that was given in the past, or that the advice could be so inapparent that it is not perceived as such by patients, or advice could be given by health professionals without it being recorded. One study on smoking advice found that, before the introduction of a pay for performance programme to incentivise advice giving, the prevalence of advice recalled by patient reports closely matched that from medical records. This diverged after the introduction of the incentive, with advice recorded in medical records being more common than patients recalled.16 Studying data from both sources can add validity to estimates of trends and factors that predispose to the delivery of lifestyle advice. This is what the authors aimed to investigate here.Research from several countries  has generally shown that a minority of patients with hypertension or diabetes receive lifestyle advice to help manage their condition.17 The current analysis included the years 2003–2017, inclusive. Information collected varies by year and the years 2002, 2007, 2008, 2016, and 2018 were excluded as they did not contain sufficient information on lifestyle advice. General practice records from the QResearch database of anonymised health records of patients from 1500 general practices throughout England who use the EMIS clinical computer system were also used. The data held include current patients and patients who have died or left the practice. Data were extracted from the QResearch database for patients aged 40–74 years between 2009 and 2017 18 who had a diagnosis of hypertension or type 2 diabetes .Data from the Health Survey for England (HSE) were used; this is an annual cross-sectional survey in which information on health and health-related behaviours is collected from participants in a nationally representative sample of the English population. Further information on the survey methodology can be obtained online.In the HSE analysis, hypertension and diabetes were defined as self-reported ‘doctor diagnosed’ hypertension/diabetes and/or ‘currently receiving treatments/advice’, excluding hypertension/diabetes during pregnancy. The HSE makes no distinction between type 1 and type 2 diabetes, and so the term ‘diabetes’ is used when discussing the HSE data henceforth (Supplementary Table S1).In QResearch, data from patients who had a coded diagnosis of hypertension or type 2 diabetes diagnosed between 2002 and 2016 were analysed. In this article, the term ‘type 2 diabetes’ is used when discussing QResearch data henceforth.In the HSE, individuals reported whether they were currently receiving medication for hypertension/diabetes. They were asked whether they were currently receiving any other treatments or advice for their hypertension/diabetes, and any person who reported receiving advice addressing behavioural risk factors for either hypertension or diabetes was coded as receiving ‘lifestyle advice’ (Supplementary Table S1).In QResearch, the proportion of those with a diagnosis of hypertension/type 2 diabetes who received medication within 1 year of diagnosis was analysed (Supplementary Table S2). A composite lifestyle advice variable was again generated (Supplementary Table S3) and the proportion of those coded as receiving lifestyle advice for hypertension/type 2 diabetes in the year following diagnosis calculated.19In HSE, sociodemographic variables included self-reported age, sex, social class, and ethnicity. Age was grouped into <35, 36–59, and ≥60 years. Body mass index (BMI) was calculated by trained nurses and categorised as healthy weight (BMI ≥18.5 to <25), overweight (BMI ≥25 to <30), and obesity (BMI ≥30).20 where quintile 1 indicates the least deprived and quintile 5 indicates the most deprived), ethnicity, and BMI . Data on BMI for those patients who had a BMI record within 1 year of diagnosis of hypertension/type 2 diabetes were extracted. For those with multiple BMI records, the reading closest to the date of diagnosis was used.In QResearch, information was available on age, sex, area deprivation index  who reported receiving lifestyle advice or medication in each survey year was calculated; and P-value of less than 0.05 was deemed statistically significant.In HSE, the prevalence of hypertension and diabetes was calculated each year. In QResearch, the proportion of patients who were provided with lifestyle advice and medication within 1 year following diagnosis in each study year was calculated. Stata 14SE  was used for all analyses. A . From 2003 to 2017 the prevalence of hypertension increased from 23.6% to 26.1% of adults in the survey and the prevalence of diabetes increased from 4.1% to 7.2%. The prevalence of hypertension and diabetes appeared abnormally low in 2004, so this year was excluded from subsequent analyses (Supplementary Table S5). From the QResearch database, 1 507 378 patients had hypertension and 569 036 patients had type 2 diabetes and were eligible for analysis .Demographic and anthropometric characteristics of the HSE responders can be found in Supplementary Table S4 In the HSE, the proportion of adults with hypertension who reported receiving lifestyle advice increased significantly from 13.8% in 2003 to 20.1% in 2017 and the proportion of patients reporting receiving antihypertensive medication increased significantly from 56.6% to 62.2% over the same period . AnalysiA large increase in the recording of lifestyle advice was apparent between 2009 and 2013, corresponding with changes in the Quality and Outcomes Framework (QOF) around this time. Alcohol intervention support or referral was the most commonly delivered individual component of the lifestyle variable with 12.6% of patients with hypertension receiving this in 2016 (Supplementary Table S6).In the HSE, the proportion of adults with diabetes who reported receiving lifestyle advice decreased over time, although this trend was not statistically significant (45.0% to 27.9%) and the proportion of those taking medication did not change significantly (77.9% to 79.0%) . AnalysiWeight management support or referral was the most commonly delivered type of lifestyle advice, with 23.9% of patients with type 2 diabetes receiving this in 2016 (Supplementary Table S6).For patients with hypertension in the HSE, adults aged under 35 were more likely to report receiving lifestyle advice than patients over 60 whereas females and patients of white ethnicity were less likely to report receiving advice than males or those from other ethnic backgrounds. Patients receiving antihypertensive medication or who were overweight were more likely to receive lifestyle advice than the comparator group .. Furthermore, patients over 35 years of age, those who were receiving medication, or who were overweight were also more likely to have a record of lifestyle advice than the comparator group  appear to be dominated by a spike from 2009 to 2013 corresponding with the introduction of a QOF encouraging provision of lifestyle advice, which is not reflected in the self-reported data.For patients with diabetes, the evidence was inconsistent, with a decline in patients reporting receiving advice but an increase in reports of advice being provided based on medical records. Associations between lifestyle advice and participant characteristics were mixed but provide evidence of differences by age, sex, ethnicity, and minor differences by socioeconomic status. For patients with hypertension who were overweight or with obesity, advice was more common, whereas for diabetes it was less common than for patients with a healthy weight.To the authors’ knowledge, this is the first study using self-reported and healthcare records to examine changes in the provision of lifestyle advice for hypertension and diabetes in England. This allowed the examination of the relationship between what a healthcare professional reports delivering and what a patient reports having received. The disparities between the two sources may suggest a need for further support to aid the implementation of lifestyle advice. A strength of this analysis is large sample sizes provided by the HSE and QResearch databases with adequate power to investigate changes in trends and associations with various sociodemographic factors.21 Relevant information was not available for every year in the HSE  and 60.8% and 33.0% of patients with hypertension and type 2 diabetes, respectively, in the QResearch database do not have a recent BMI recorded.There are, however, several limitations. The fact that the results are not wholly consistent may reflect limitations in the methods employed. It is possible that not all interventions relating to lifestyle advice have been captured in the electronic healthcare records, potentially leading to an under-recording of lifestyle advice provision, for example, the current study did not include codes for referral to diabetes structured education that may include some aspects of lifestyle advice. It may also be that patients are receiving lifestyle advice from other sources such as support groups, which may not have been recorded in their medical records.22 Finally, self-reported information in the HSE may be biased if participants do not recall information appropriately or because of social desirability bias.In the HSE data, the current study defined hypertension and diabetes based on self-reported data from participants, rather than direct measurements of blood pressure and glycated haemoglobin (HbA1c) obtained during a nurse visit. The QResearch population is broadly representative of the national population and thus findings ought to be similar to the data obtained from the HSE. However, the questions asked of the two populations were slightly different, with HSE participants being asked if they are currently receiving lifestyle advice whereas in QResearch this advice is recorded within 1 year of diagnosis. The ambiguity of the question asked in the HSE may lead to some under-reporting of receiving lifestyle advice, dependent on the participants’ interpretation of ‘currently receiving’. Furthermore, as the HSE does not make a distinction between type 1 and type 2 diabetes, it is likely that the populations in the diabetes analysis are subtly different. Type 1 diabetes is estimated to account for around 8% of all diabetes diagnosis in the UK and, for this patient cohort, lifestyle advice is not indicated as a treatment, beyond general health improvement measures.23,24 Research from the Netherlands has shown that lifestyle advice was provided in only 40% of hypertension-related primary care consultations,14 and data from Australia showed that less than a third of patients with hypertension received advice to reduce salt intake.15 In one study in the UK of uncomplicated stage 1 hypertension, only a third of patients received lifestyle advice, whereas half were prescribed antihypertensive medication.11 For those with type 2 diabetes, studies from Ghana and the US found that just over half of patients receive some form of lifestyle advice.12,13This study contributes new evidence to the growing body of literature suggesting that the prevalence of receiving lifestyle advice for hypertension or diabetes is low, despite lifestyle advice being recommended in clinical guidelines as the first-line intervention for both conditions.25 as well as changes to QOF indicators in April 2009 that encouraged advice for physical activity, smoking cessation, safe alcohol consumption, and healthy diet.26 There was a marked decline in 201427 after this indicator was removed. The trend in patients’ reports of hypertension-related advice did not change during this period. The impact of this QOF indicator on the recording of lifestyle advice for patients with hypertension has previously been shown in a time series analysis from the Clinical Practice Research Datalink.11In the recording of lifestyle advice provision by healthcare professionals, there was a marked increase in the proportion of patients with hypertension recorded by GPs as receiving lifestyle advice between 2009 and 2013. This coincides with both the introduction of the NHS health check programme in April 200928 Again no corresponding change is noted in patient reports from the HSE. These examples imply that changes in QOF indicators influence GP recording behaviour, but the apparent lack of corroboration from patients’ reports raises concerns that this may not reflect improved performance in delivery of meaningful or helpful support for behavioural management of these conditions.11Furthermore, the decline in the recorded delivery of lifestyle advice for patients with type 2 diabetes from 2013 may partly be explained by the retirement of a QOF indicator supporting the need for patients to have a dietary review by a suitably qualified professional in the preceding 12 months.9 This result contrasts with a previous study in the US where increasing BMI was positively associated with receiving advice to exercise more among those with diabetes.29 However, a smaller study from Ghana of 378 patients with type 2 diabetes found no significant association between receipt of weight management counselling and weight status.13 It may be that these patients are referred instead to structured educational programmes such as Diabetes Education and Self-Management for Ongoing and Newly Diagnosed (DESMOND) and X-PERT where they receive lifestyle advice. Read codes for these types of diabetes education programmes were excluded from the analysis as they are general educational programmes where healthcare professionals in primary care could theoretically refer patients without directly discussing lifestyle advice.The finding that individuals with diabetes who were overweight or with obesity are less likely to receive lifestyle advice is unexpected, especially given the growing attention to the importance of weight management to treat type 2 diabetes.30 Another study using NHANES data found that males and white patients who were overweight or with obesity but no chronic health conditions were less likely to receive lifestyle counselling than other ethnicities.31 It is important to ensure that inconsistencies in the offer of lifestyle advice do not contribute to health inequalities.There is relatively little research investigating the likelihood of receiving lifestyle advice for chronic diseases in relation to demographic characteristics and, as observed in the current study when comparing trends for hypertension and diabetes, the evidence is inconsistent. A previous US study using data from the National Health and Nutrition Examination Survey (NHANES) found that males and black patients were more likely to receive lifestyle counselling for hypertension than females and white patients.Despite clinical guidelines recommending lifestyle advice and clear evidence showing the benefit of lifestyle modification to treat diabetes or hypertension, only a minority of patients with hypertension or diabetes in England are receiving lifestyle advice whereas a much larger proportion of them are receiving medication for hypertension or diabetes.Although increasing somewhat, most patients are still missing out on opportunities to improve the management of their condition and reduce the risk of cardiovascular disease. Guidelines and evidence by themselves, and probably the QOF, have proved insufficient to change clinical behaviour and further support for effective implementation is needed to realise the potential benefits.


Essential oils have been used for centuries for their calming properties. This alternative medicine therapy is gaining popularity in the inpatient setting for symptom management including pain, anxiety, nausea, and insomnia. The purpose of this project is to evaluate the effectiveness of aromatherapy complement as an alternative and/or treatment for pain and anxiety ion the acute care setting at on Health and Hospital System, The target population for this study was patient who were receiving care in the Surgical Services inpatient units including burn patients.This study included all surgical patients admitted to one hospital and this is an analysis of the burn cohort enrolled thus far in this study. All adult burn patients that met inclusion criteria were included to evaluate the impact of aromatherapy on the administration of pain and anxiety medications (PANX). After introducing the patient to the study and obtaining informed consent a Lavender-Sandalwood scented aromatherapy sticker was placed on the patients' gown. The aroma last from the sticker last for twelve hours and could be replaced upon patient request. The stickers were used for a total of three days. Survey data was collected to describe the experience with the sticker as well as PANX medication administration and demographic information. Pain scores were recorded for each patient before PANX administration within the 72 hour time period after surgery or burn wound care procedures.To date a total of fourteen patients were enrolled in the study mean age was 44 years old, 71% of the patients were male and the mean TBSA was 5%.Two patients withdrew one because the scent gave them a headache and one because there were no study logs completed. Each of the twelve patients used a total of 6 stickers over the 3 days of the intervention. Prior to the start of the study the average pain score was 8.6 (range 7-10). On day one of the intervention the mean pain score was 4.75 (range 3-8), day two 4.25 (range 2-8), and on day three 4.3 (range 0 - 9). Post intervention pain scores were 5.75 (range 0-9). Comparison of the pain scores pre and post intervention were statistically significant t= -2.904(95% CI = -4.85 to -0.81) p = 0.0082. Of note patients reported that sleep was improved while using the aromatherapy sticker.Aromatherapy may provide a natural alternative to reduce opioid pain medications and improve sleep in the burn patient thereby improving long term outcomes.


Dry socket and post-extraction pain are typical discomforts experienced by patients after tooth extraction. In this study, we inserted gauze coated with oxytetracycline-hydrocortisone ointment into the extraction socket immediately after lower third molar extraction and then evaluated the occurrence of dry socket and post-extraction pain compared with gauze non-insertion.This retrospective study was carried out on patients undergoing lower third molar extraction in the Department of Oral Surgery at Shizuoka Prefectural General Hospital in Shizuoka, Japan from November 2018 to October 2019. A comparison was carried out between a gauze-insertion group and a non-insertion group. The occurrence versus non-occurrence of dry socket was determined, and degree of pain was assessed based on a visual analogue scale (VAS) and on patients reporting the number of loxoprofen sodium oral analgesic tablets (60mg/tablet) that they had taken. Dry socket was defined as patient-reported spontaneous pain that did not subside 1 to 3 days postoperatively. Spontaneous post-extraction pain was recorded four times: on the operative day, on the first postoperative day (POD1), on POD3, and during suture removal (POD7).The occurrence of dry socket was lower in the gauze-insertion group than in the non-insertion group . The results also showed that both VAS-defined pain level and the number of analgesic tablets taken were lower in the gauze-insertion group than in the non-insertion group on POD3 and POD7.Inserting gauze coated with oxytetracycline-hydrocortisone ointment into the extraction socket immediately after third molar extraction reduces the occurrence of both dry socket and post-extraction pain. Dry socket occurs when a clot becomes partially or completely detached from the extraction site before the wound has healed , 2. It iThe methods of preventing dry socket that have been studied include administering chlorhexidine gel  or plateSome research has focused on the most common treatment for dry socket, which involves inserting ointment containing antibacterial or steroidal agents into the extraction socket and then covering the site with a surgical pack . A studyHydrocortisone is an adjuvant used in complex surgical procedures that is well known for its potent anti-inflammatory properties . In the This retrospective study was carried out on patients who underwent lower third molar extraction in the Department of Oral Surgery at Shizuoka Prefectural General Hospital from November 2018 to October 2019.Two groups of patients were studied. In the gauze-insertion group, surgical gauze containing X-ray contrast medium  was coated with oxytetracycline-hydrocortisone ointment  and inserted into the socket immediately after tooth extraction, followed by suturing. The non-insertion group did not receive this treatment prior to suturing. Gauze containing X-ray contrast medium was used in order to allow the gauze to be identified by imaging in the event that it came loose from the socket and was accidentally swallowed. From November 2018 to March 2019, the decision whether to insert gauze was made independently by the attending physician for clinical need; however, from April 2019, only gauze-insertion procedures were performed. Patients were excluded from analysis if they had simultaneous extraction of adjacent teeth or if they had taken medication for the extraction site prescribed by a physician outside our hospital.This study was approved by the ethics committee of Shizuoka General Hospital (SGHIRB#2019013). The procedure in which gauze coated with oxytetracycline-hydrocortisone ointment is inserted into the socket immediately after extraction was certified by the Clinical Ethics Committee for Medical Procedures of Shizuoka General Hospital based on the 1980 notification on off-label use from the Director of the Health Insurance Bureau at the Ministry of Health, Labour and Welfare of Japan .chiken-sougou@shizuoka-pho.jp). All requests must be accompanied by a plan detailing the analysis to be carried out on the data and will be subject to approval by the hospital’s Steering Committee.All data were fully anonymized before being accessed for this study. For retrospective studies using anonymized data, the Japanese Ethical Guidelines for Medical and Health Research Involving Human Subjects do not require information on the nature of future data disclosure to be included in informed consent agreements. Following these guidelines, the purpose and methods of this study were disclosed to potential participants on the hospital website, along with the recognition of their right to decline to participate in the study. Therefore, due to ethical limitations, the raw data for this study cannot be made freely available in the manuscript, supporting information files, or public repositories. Researchers seeking to access the dataset can file a request with the Clinical Trials Management Office at Shizuoka General Hospital  . A full-G.B. Winter classification, impaction condition, and maximal mouth opening were assessed by a doctor. The Winter classification had two indexes representing the difficulty of tooth extraction: class classification  and position classification  . ImpactiPrior to surgery, patients completed a questionnaire on smoking and inflammation history. The smoking history included whether the patient had ever smoked. The inflammation history included the presence or absence of gingival pain and swelling around the lower third molar to be extracted prior to the first visit. This questionnaire is routinely carried out for patients undergoing third molar extraction at Shizuoka General Hospital.A diagnosis of dry socket was determined by the doctor who had carried out the surgery when patients reported spontaneous post-extraction pain that did not subside 1 to 3 days postoperatively , 3.Spontaneous post-extraction pain was measured in the following manner. After surgery, patients returned to hospital on the first postoperative day (POD1), at which time they were given a form on which to record their pain responses and were instructed by their doctor on how to use it. Degree of pain was assessed based on two measures: A visual analog scale (VAS) that ranged from 0 (no pain) to 10 (worst pain), and the number of loxoprofen sodium analgesic tablets (60 mg/tablet) taken by patients. Responses for both measures were entered by patients for the operative day, POD1, POD3, and the day that the sutures were removed (POD7).Continuous variables are presented as mean and standard deviation, and categorical variables are presented as frequency and percentage. The Wilcoxon rank-sum test and the chi-square test were used to compare the background of the gauze-insertion group and the non-insertion group and to compare variables related to the occurrence of dry socket.Comparisons of outcomes between the two groups were conducted using a logistic regression analysis for the binary outcome of the occurrence of dry socket and a linear regression analysis for the continuous outcome of the VAS value of spontaneous pain perception. In the logistic regression analysis, odds ratio (OR), 95% confidence interval (95% CI) based on the Wald test, and corresponding P-value were calculated. In the linear regression analysis, least-square means, 95% CI based on the Wald test, and corresponding P-value were calculated. Multivariate models were adjusted by variable in relation to the differences between the two groups and to the occurrence versus non-occurrence of dry socket. A P-value of < .05 was considered statistically significant. All analyses were performed using SAS version 9.4 .A multivariate logistic regression analysis adjusting for sex, the class classification of the G. B. Winter classification, and maximal mouth opening indicated a lower incidence of dry socket in the gauze-insertion group .The degree of spontaneous post-extraction pain was evaluated with two measures: the VAS and the number of loxoprofen sodium oral analgesic tablets (60 mg/tablet) taken. The above results suggest that insertion of gauze coated with oxytetracycline-hydrocortisone ointment into the extraction socket immediately after third molar extraction reduces both the occurrence of dry socket and the degree of post-extraction pain. Dry socket was defined as the occurrence of spontaneous pain that did not subside 1 to 3 days after surgery, and the degree of spontaneous post-extraction pain was measured by VAS and by the number of oral analgesic tablets taken by patients. We found that the occurrence of dry socket was lower in the gauze-insertion group (0.9%) than in the non-insertion group (19.6%) (p<0.001). We also found that both the VAS value and the number of tablets taken was lower in the gauze-insertion group than in the non-insertion group on POD3 and POD7, indicating that spontaneous post-extraction pain was suppressed.Dry socket results from the detachment of the blood clot from the extraction socket. This detachment can be caused both by the enhancement of the fibrinolytic system in the socket and by mechanical stimulation . HyperacOxytetracycline-hydrocortisone ointment consists of a combination of hydrocortisone and oxytetracycline hydrochloride. Hydrocortisone has a local anti-inflammatory effect, and oxytetracycline hydrochloride has an antibacterial effect and also suppresses fibrinolysis of the socket . The addSeveral studies on preventing the incidence of dry socket and post-extraction pain have been reported. A study on the preventive effect of chlorhexidine on dry socket reported that the incidence of dry socket was 7.5% for the topical administration of chlorhexidine gel into the socket and 25% for rinsing of the mouth with chlorhexidine mouthwash . In seveA common treatment for dry socket is to insert ointment containing an antibacterial steroidal agent into the extraction socket and then cover the area with a surgical pack. One study showed that applying gauze coated with chlortetracycline ointment to the socket immediately after extraction was effective in preventing dry socket, but not in reducing pain . In the The present study has several limitations. First, it was an observational study, and the assignment of patients to the gauze-insertion and non-insertion groups was not randomized. We tried to improve the exchangeability between groups by adjusting for patient background factors. We did not investigate additional factors that might affect dry socket, such as bone mass, flap range, and operation time, but these factors are covered by the G. B. Winter classification , 22. TheThis study suggests that inserting gauze coated with oxytetracycline-hydrocortisone ointment into the extraction socket immediately after lower third molar extraction reduces the occurrence of both dry socket and spontaneous post-extraction pain.


Rotator cuff tendinitis has been treated using various methods including physiotherapy, steroid injections and recently platelet rich plasma (PRP). Most of these methods aim at giving symptomatic relief rather than addressing the pathology. There is no clear consensus over the benefit of using PRP for tendinitis. We decided to do a prospective clinical study to demonstrate the efficacy of PRP and study the functional outcome in the treatment of rotator cuff tendinopathy.Patients with shoulder pain for more than three months not responding to NSAIDs or physiotherapy with a diagnosis of rotator cuff tendinitis, confirmed by MRI, were included in the study. Patients with rotator cuff tear or any other shoulder pathology were excluded. We included a total of 30 patients who received 5ml of landmark guided PRP injection in the subacromial space followed by a six-week exercise program. Patients were followed-up at 3, 6 and 12 weeks. and were assessed clinically using the VAS, SPADI and Constant and Murley Score.VAS score of patients improved from a pre injection score of 7.4 to a score of 1.9 in the 12th week. The mean SPADI score and Constant score improved from a pre injection score of 73.33 and 39.57 to a post injection score of 18.1 and 86.47, respectively.Platelet Rich Plasma injections showed good to excellent early results, in patients with rotator cuff tendinopathy with improvement in VAS, SPADI and Constant scores. Conservative treatment measures for cuff tendinopathies have given variable results, because most of these measures aim at giving symptomatic treatment rather than addressing the pathology3.Traditional treatment methods include non-steroidal anti-inflammatory drugs, corticosteroid injections, ice, rest, and bracing or immobilisation and physiotherapy4.Corticosteroid injections are uselful in only acute and subacute tendinits and some reports have said that they cause an inhibition in collagen synthesis which may lead on to tendon failureThe inadequacy of these therapies in some cases calls for new research. Research in the last decade has improved our knowledge about the tendon biology and pathology, resulting in the development of biological interventions for the disorders of the tendons.5. Therefore, treatment should not only target pain reduction, but also provide an environment where healing is stimulated, promoting tissue regeneration and ultimately pain relief without any recurrences.The primary goal is to get pain relief and to increase the functional capacity of the involved tissue. In tendinitis there is a lack of inflammatory response as reported in histological studies resulting in poor tendon healing6. Platelet Rich Plasma (PRP) therapy is the readily available autologous “bedside” injectable orthobiologic, which is gaining widespread use. It increases healing potential, mediates inflammatory processes and reduces pain through the release of mediating amines. PRP has become an important prophylactic alternative in pain medicine and in the treatment of chronic tendon pathology7.Along with new insights regarding tendinopathies, a promising new era of biologically based cellular therapy has emerged. Orthobiologics involve the inclusion of biology and biochemistry in the development of bone and soft tissue replacement materials for skeletal and tissue healing8.Platelet-rich plasma is an autologous biomaterial obtained by centrifuging whole blood. PRP may be defined as a fraction of autologous plasma with platelet concentration above the baseline. Platelets are responsible for promotion of hemostasis, formation of new connective tissue and revascularisation. Thus peritendinous injection of PRP acts by limiting damage and promotes healing mechanisms in the tendons involved. It acts by its anti-inflammatory, anabolic and milieu interior altering mechanism through release of growth factors present in the platelets11. We decided to do a prospective clinical study to demonstrate the efficacy of PRP and to evaluate the functional outcome in the treatment of rotator cuff tendinopathies.Various studies have shown the positive effects of PRP in different clinical situations and it is a safe strategy to deliver the natural mixture of biologically active molecules within the tendon compartment to induce positive changes in the tendon microenvironmentPatients who presented to the outpatient clinic with shoulder pain and diagnosed as rotator cuff tendinopathy were enrolled in our study. Our inclusion criteria were patients more than 18 years of age; pain more than three months refractory to conservative treatment, rotator cuff tendinopathy as diagnosed by clinical examination and ultrasound/MRI. We excluded patients with concomitant rotator cuff tear, arthritis or bony lesions of shoulder, patients with inflammatory disease e.g., rheumatoid arthritis and patients who had local pathologies like skin lesions or infection.The study was carried out after approval from our institutional ethics committee. The period of our study was from November 2015 to October 2017. We included a total of 30 patients who met our inclusion and exclusion criteria. From all patients a detailed clinical history of the patient was elicited. For all patients, a general physical examination was done, and the shoulder involved was examined. Tenderness if any, the range of motion, impingement signs, and rotator cuff power was recorded. Plain antero-posterior radiograph, axillary view radiographs and Ultrasound or MRI of the shoulder was taken in all patients. Patients were asked to fill the patient information sheet and were explained in detail about the study and informed written consent was obtained. The baseline SPADI (shoulder pain and disability index) score, Constant and Murley score and the VAS score were assessed and then patients were planned for intra-articular injection.Under all aseptic precautions, about 20ml of blood was drawn from the antecubital vein of the patient and centrifuged to get 5ml to 6ml of platelet rich plasma. 1ml of the sample was sent to check for the platelet count to establish platelet concentration. The PRP without any buffering or activating agent was taken in a syringe. Using sterile aseptic precautions 5ml of prepared PRP was injected 1cm below and lateral to the posterolateral corner of the acromion into the subacromial space around the rotator cuff tendon. Sterile dressing was applied at the injection site. The patient lay supine for about 15 minutes without moving his shoulder. Patients were strictly observed for complaints such as pain, swelling and redness following injection. For pain ice pack application was given and patients who had severe pain were given either oral Acetaminophen or Tramadol. Patients were taught and told to do rotator cuff strengthening exercises from the 1st week onwards.Patients were followed at 3rd, 6th, and 12th week. At each follow-up patient were assessed clinically for pain relief and range of motion. VAS score, SPADI score and Constant and Murley Score were recorded at each visit. Adverse reactions if any were noted.The power analysis indicated a beta of 100%. Data was collected using a semi structured proforma. The data was analysed in the study using SPSS version 23. All the outcome variables had at least once a not normal distribution at some point in the timeline found by applying Shapiro Wilk test. A p value of less than 0.05 indicated not normal distribution. To compare the mean scores collected pre injection and post injection, Friedman’s test was employed due to non-parametric nature of data and presence of four related groups. A p value of <0.05 was considered as statistically significant.A total number of 30 patients with rotator cuff tendinopathy were selected based on our inclusion and exclusion criteria. None of our patients were lost to follow-up. Majority of patients were between 30-50 years (43.3%), 36.7% of patients were more than 50 years and 20% of the patients were less than 30 years old .Majority of patients were males 17 (56.7%) and rest 13 (43.3%) of patients were females. Right shoulder was affected in 20 (66.7%) patients and left in 10 (33.3%).The mean platelet count was 223.2±41.4×103⁄ μL in the whole blood samples and 994.9±210.3×103⁄ μL in the PRP samples. A 4-fold increase was seen in the number of platelets in PRP compared with whole blood.The mean Visual Analog Scale score of patients improved from a pre injection score of 7.4±1.19 to a score of 1.9±1.09 in the 12th week. The magnitude of VAS had decreased significantly post injection with P value of less than 0.05 and with a strong effect size  .The pre injection mean SPADI score was 73.30 ± 9.02. Post injection SPADI at third, sixth and twelfth weeks were 55.76 ± 12.52, 38.56 ± 15.91 and 18.10 ± 10.65, respectively. The magnitude of SPADI had decreased significantly post injection with P value of less than 0.05 and with a strong effect size  .The pre injection mean constant and Murley score was 39.57 ± 17.02. Post-injection mean, Constant, and Murley score at third, sixth and twelfth weeks were 56.80 ± 14.36, 70.17 ± 14.68 and 86.47 ± 8.59, respectively. The magnitude of Constant and Murley score had increased significantly post injection with P value of less than 0.05 and with a strong effect size  .Over time the pre-injection VAS median of 7.5 had decreased to 6, 3.5, and 2 in 3rd, 6th, and 12th week, respectively . Pre injPre-injection, majority of the patients (76.7%) had a Constant Murley score less than 50 . The pre12. The treatment of tendinopathy is aimed at addressing these etiological factors.Rotator cuff tendinopathy has a multifactorial origin, which may include both intrinsic, and extrinsic factors. The intrinsic factors include degeneration of the cuff, which is age related and vascularity changes in the tendon substance. Extrinsic factors like biomechanical and anatomic dysfunctions, which can lead on to impingement, overuse, and overload of the tendons8. We evaluated our results and compared them with those obtained by various other studies in literature.PRP injections have been used over the past 10 years for chronic tendon injuries because of its properties that help in collagen synthesis, proliferation of tendon cells and improved vascularisation of the tendonet al12, Mautner K et al9, Wesner et al10, Scarpone et al11 who had average age of 45.5 years, 48.6 years, 44.6 years, 46.2 years, respectively. Thus, rotator cuff tendinopathy is more common in the middle age, as compared to rotator cuff tears, which is more common in the elderly.In our study, rotator cuff tendinopathy was more common in the 4th and the 5th decade with a mean age of 43.3 years. The average age in our study was comparable to the studies of Kesikburun et al11 in their study of PRP for chronic tendinopathy had a higher male preponderance with 15 male and only 4 female patients. The higher male preponderance could be because males are more likely to be involved in heavy physical activities like manual labour, sports activities etc. Most of the males in our series of patient were either manual labourers or farmers.Our study had a male preponderance with 17 male and 13 female patients. Scarpone et al9 did a retrospective study where they studied 180 patients. Platelet rich plasma injection for chronic tendinopathy was given in all these patients. In their study the mean VAS score improved from 7 to 2 at the end of 6 months, whereas in our study mean VAS score reduce from 7.4 to 1.9 at 12th week. They reported as moderate improvement in pain symptoms (>50%) with multiple PRP injection for chronic tendinopathy, our study had good results with single PRP injection. There was significant improvement in pain in most of our patients and they were able to get back to their activities of daily living.Mautner et al10 did a randomised control trial on patients receiving PRP and reported clinical improvement in pain (>1.5/10 on VAS), disability score (>15 points DASH change), and tendon pathology while those receiving placebo injections did not. In the observational cohort, statistically and clinically significant improvements in pain and disability were observed.Wesner et al11 in their prospective open label study on 18 patients who received a single PRP injection, concluded that PRP resulted in safe, significant, and sustained improvement in pain and function. Twelve participants were “completely satisfied”, five patients were “satisfied”, and one participant was “unsatisfied”. The mean VAS score improved from 7.5 to 0.5 at 12th week. Our results were similar with mean VAS 7.4 to 1.9 at 12th week, as they had good improvement in VAS scores and majority of patients were satisfied.Scarpone et al12 did a comparative study of PRP versus Saline injection in 40 patients with rotator cuff tendinopathy. In their study the SPADI score, which was 77.5 reduced to 27.6 at the end of the 12th week in the patients who were treated with PRP. In our study the mean SPADI score reduced from 73.3 to 18.1 at the end of 12th week. We had better reduction in SPADI score. In their study mean VAS score reduction was from 8 to 3 at 12 weeks and in our study mean VAS score reduced from 7.4 to 1.9 at the 12th week. They concluded at one year follow-up, a PRP injection when compared to placebo was no more effective in improving the quality of life, pain, disability, and shoulder range of motion in patients with chronic rotator cuff tendinopathy who were treated with an exercise program.Kesikburun et al13 in their meta-analysis of randomised controlled clinical trials in which they included 18 studies, found that there is good evidence to support the use of a single injection of highly cellular leucocyte rich PRP under ultrasound guidance in tendinopathy. The preparation and the technique of intra tendinous injection technique of PRP have a clinical significance.Jane Fitzpatrick et al14 in their randomised controlled trial compared dry needling vs PRP in patients with supraspinatus tendinosis in 39 patients. They reported that the platelet rich plasma injection leads to a reduction of pain and disability progressively, in comparison with dry needling. The mean SPADI index at 6 months was 17.7 ±3.7, for the PRP injection group and 29.5 ± 3.8 in the dry needling group (P<0.05). They concluded that PRP injections are safe and useful for rotator cuff disease. In our study the mean SPADI score was 18.1 at the 12th week.Rha We used only a single injection of PRP. Serial injections are one of the controversial topics in PRP injection. A second injection can be performed at one to two months if no therapeutic effect is seen, but in most of our patients a single injection was effective.All our injections were landmark guided, given by a single surgeon trained in shoulder arthroscopy. Ultrasound guide may improve the accuracy of the injections, but the added cost was the reason we did not give the injections guided by ultrasound.PRP is an evolving treatment modality gaining momentum in primary care, rehabilitation, and sports medicine applications. PRP may provide a minimally invasive outpatient treatment for refractory rotator cuff tendinopathy thus providing a less expensive alternative modality to surgery with a reduced potential for operative side effects and adverse events. Physiotherapy is an important part of the treatment, post PRP injection. Further studies with a larger number of patients will prove the efficacy of PRP in rotator cuff tendinopathy. Our study fortunately had no complication like needle breakage, local inflammation, or infection, except for the pain at the injection site for 24 to 48 hours.The limitations of our study were that we had a smaller sample size and no controls, we did not do a post injection ultrasound or MRI to evaluate the tissue regeneration and healing. This may be, carried out in subsequent research efforts. Future studies with a longer follow-up are being planned.Platelet Rich Plasma injections showed good to excellent early results, in patient with rotator cuff tendinopathy with improvement in VAS, SPADI and Constant scores. It can be recommended for patient with rotator cuff tendinopathy not responding to physiotherapy.


Chronic pain is highly prevalent in treatment-seeking opioid-dependent patients; therefore, this comorbid presentation is an important clinical consideration for both addiction and pain specialists. The objectives of the present study were to examine whether the direction of causal attribution of opioid dependence disorder and chronic pain resulted in two distinct clinical populations, and, if so, to compare treatment received during the 5-year follow-up period.n = 252). A range of health- and addiction-related instruments were used at study inception. Treatment characteristics were obtained for the follow-up period from national health registers.Participants comprised opioid-dependent patients with chronic pain who reported a perceived causal relationship, in either direction, between the development of these two conditions  were characterised by poorer pain-related health, more illicit cannabinoid use (p = 0.031), more frequent illicit use of opioid analgesics (p = 0.025) and they were in receipt of higher doses of prescribed opioid analgesics. Those reporting that opioid dependence disorder caused pain  were characterised by poorer overall physical health (p = 0.002), more severe psychiatric symptoms and more overall drug use (p = 0.001).Those reporting that pain caused opioid dependence disorder (Two distinct clinical populations were identified, determined by how participants perceive the causal relationship between opioid dependence disorder and chronic pain. These two populations have differing clinical profiles and treatment requirements: those reporting that pain caused opioid dependence disorder were characterised by poorer pain-related health and more illicit use of drugs with analgesic properties; and those reporting that opioid dependence disorder caused pain were characterised by more overall use of substances, multiple substance use and more intravenous substance use and poorer general health. Identifying the causal direction, where such a relationship exists, could help addiction and pain services to develop more effective, individualised treatment strategies. Patients in OAT with comorbid CP are associated with greater medical and psychiatric health burdens3 in addition to relatively severe and enduring substance dependence.5 Different disease trajectories leading to this comorbid presentation may be associated with clinical subgroups that have differing OAT and analgesic requirements and distinct profiles of medical and psychiatric morbidities that may impact on the effectiveness of standardised treatment strategies.Chronic pain (CP) is reported in up to 68% of opioid-dependent patients in receipt of opioid agonist therapy (OAT); examined the relative temporal onset of chronic, non-arthritic pain and substance use disorders (SUDs), which included alcohol, in 632 participants. They found that 56% (n = 351) reported that the onset of SUD preceded that of pain, 38% (n = 243) reported that the onset of pain preceded that of SUD and the remaining 6% (n = 38) reported that the onset of both conditions occurred within the same year. Ilgen’s work involved a national survey of the general population. In contrast, the present study involved a treatment-seeking sample of people diagnosed with opioid dependence disorder (ODD), and asked about their beliefs about the causal relationship in the development of CP and ODD rather than inferring this relationship based on temporal patterns. For comparison, an ICD-10  diagnosis of opioid dependence (OD) generally corresponds to a Diagnostic and Statistical Manual of Mental Disorders  diagnosis of either moderate or severe opioid use disorder. This issue is discussed in greater detail in the ‘Method’ section.In the only published study to address this so far, Ilgen et al.9 or addiction-like behaviour borne out of a desire to control unmanaged pain.11 Conversely, pain may develop in patients with ODD as a result of opioid-induced hyperalgesia, which is more evident in patients with ODD than in patients with CP, or due to the higher risk of physical injury15 and the sequelae of substance use. In a comprehensive examination of this topic, Manhapra et al. suggest that patients with CP who are prescribed long-term opioid analgesia may develop an iatrogenic syndrome, referred to as complex persistent opioid dependence (CPOD). CPOD is considered as a clinical condition distinct from opioid use disorder with comorbid CP. In contrast to the clinical presentation of patients with opioid use disorder , CPOD is characterised by poor pain control, declining function, psychiatric and medical instability, and aberrant behaviours. As the authors further highlight, people with CPOD require different treatment approaches to those with a primary diagnosis of opioid use disorder and are likely to feel alienated by such a diagnosis. The principal aim of the present study was to establish whether patients whose ODD led to CP presented with different clinical profiles and treatment requirements from patients whose CP led to ODD. Two hypotheses were examined:While the onset of ODD and CP may be unrelated, some patients may develop ODD as a result of analgesic opioid exposureAmong people who had both ODD and CP, two clinically distinct groups would be identified based on the patient-attributed direction of the causal relationship between CP and ODD;The characteristics associated with treatment for ODD and CP would differ between these two groups at both study inception and during the follow-up period.Participants were drawn from the cohort of patients treated in an NHS  Substance Misuse Service in a Scottish Health Board area. Patients are accepted for treatment within this service if, on assessment, they are diagnosed with OD in accordance with the World Health Organization’s ICD . To avoid confusion, the term, ‘opioid dependence disorder’ (ODD), has been used throughout, since the abbreviation for ‘opioid dependence’ (OD) is commonly understood to indicate overdose. An integral component in obtaining a diagnosis of ODD is that patients must demonstrate increasing tolerance to opioids and a physical withdrawal state on cessation of opioids. On acceptance into treatment, patients commence OAT, which, at the time of the present study, comprised methadone maintenance therapy exclusively. OAT opioid prescriptions were administered by the NHS Substance Misuse Service; however, opioid analgesic prescriptions, where applicable, were administered by other NHS services, largely within the primary care setting. For comparison, there are two ICD-10 codes that correspond to a DSM-V diagnosis of OUD: (1) F11.1 (‘opioid abuse’); and (2) F11.2 (‘opioid dependence’). Generally, the former corresponds to a DSM-V diagnosis of mild OUD, and the latter corresponds to DSM-V diagnoses of moderate or severe OUD. The present study used the 12-month threshold since, in a clinical population familiar with persistent, debilitating conditions, this was considered as the best indication of truly ‘chronic’ pain, an approach that has been used in other studies.18 Those that reported having had pain for less than 12 months were excluded from the study since they were considered to form a small, relatively heterogeneous group. No participants were lost during the course of the study: as discussed below, since only anonymised data were used, participants were not required to consent to participation.Participants recruited to the present study were those with CP who were in treatment in the service and who reported a perceived causal relationship, in either direction, between the development of CP and ODD. Patients who reported no causal relationship were excluded from the study since they were considered to form a relatively heterogeneous group, characterised by the absence, rather than presence, of clinical characteristics in common. Three temporal thresholds have been established to identify CP: 3, 6 and 12 months. was designed to assess the sensory and reactive dimensions of pain. The BPI-SF has demonstrated adequate validity and reliability in patients with CP and in patients receiving OAT. In the current sample, the BPI-SF evidenced excellent internal consistency (Cronbach’s α = .91). Following the administration of the BPI-SF, three additional questions were asked: (1) ‘For how long have you had your current pain problem?’; (2) ‘Do you believe that your pain problem was taken seriously by your doctor?’ and (3) ‘Do you believe that your pain problem caused your ODD, that your ODD caused your pain problem, or that they are unrelated?’.The 9-item Brief Pain Inventory – Short Form (BPI-SF) was designed for research purposes in populations with drug and/or alcohol problems. This instrument was used to determine illicit use of specific substances, frequency of use  and route of administration  and intramuscular). The specific illicit substances listed in the MAP are heroin, methadone, benzodiazepines, cocaine powder, crack cocaine, amphetamines and cannabis. There is also an opportunity to list other illicit substances used, including the frequency of use and the route of administration. Finally, the use and non-use of specific substances reported in the MAP was verified by performing urinalyses. It is important to note that, while the term, ‘illicit’, is used throughout this article, a proportion of patients may have been engaging in nonmedical use of substances (i.e. use of prescribed medication in a non-prescribed manner), which would apply, largely, to some patients misusing opioid analgesics and benzodiazepines that had been prescribed to them for therapeutic purposes. Scores on the MAP physical and mental health subscales range from 0 to 40, and higher scores are associated with poorer health. The MAP has demonstrated adequate validity in substance users; however, its psychometric properties have not been examined in CP samples. In the current sample, the MAP demonstrated good internal consistency (Cronbach’s α = .88).The 60-item Maudsley Addiction Profile (MAP) was designed as a screening tool to indicate any psychiatric condition. The Likert-type scoring method was used and a threshold of ⩾24 was applied . It has been shown to have the ability to accurately detect diagnoses in accordance with the Composite International Diagnostic Interview (CIDI). The GHQ-28 has demonstrated adequate validity within opioid-dependent populations; however, its psychometric properties have not been examined in CP samples. In the current sample, the GHQ-28 demonstrated good internal consistency (Cronbach’s α = .89).The 28-item version of the General Health Questionnaire (GHQ-28) assesses the level of psychological global distress. Total scores range from 0 to 136, and a threshold of ⩾34 was used to indicate clinical status. The CORE-OM has demonstrated adequate validity within a healthy volunteer sample; however, its psychometric properties have not been examined in CP or opioid-dependent samples. In the current sample, the CORE-OM demonstrated acceptable internal consistency (Cronbach’s α = .80).The 34-item Clinical Outcomes in Routine Evaluation – Outcome Measure (CORE-OM) was designed as a diagnostic screening tool to identify social phobia in accordance with DSM-IV criteria. Using receiver operating characteristic analysis, the authors identified that the optimal balance between sensitivity and specificity (both >80%) was achieved using a diagnostic threshold of 7.38 . The SPDQ has demonstrated adequate validity within a sample of undergraduate students; however, its psychometric properties have not been examined in CP or opioid-dependent samples. In the current sample, the SPDQ demonstrated good internal consistency (Cronbach’s α = .86).The 16-item Social Phobia Diagnostic Questionnaire (SPDQ) was designed to measure patient satisfaction with OAT treatment. Total scores range from 0 to 40, and higher scores represent greater treatment satisfaction. The TPQ has demonstrated adequate validity within an OAT sample; however, its psychometric properties have not been examined in CP samples. In the current sample, the TPQ demonstrated acceptable internal consistency (Cronbach’s α = .78).The 10-item Treatment Perceptions Questionnaire (TPQ)https://www.gov.scot/collections/scottish-index-of-multiple-deprivation-2020/). In accordance with SIMD recommendations, quintiles 1–2 were used to indicate relative socioeconomic deprivation and quintiles 3–5 were used to indicate relative socioeconomic affluence.Demographic data were obtained from the NHS Community Health Index (CHI) dataset. These data comprised gender, age and socioeconomic status using Scottish Index of Multiple Deprivation (SIMD) quintiles : community-dispensed prescribing; general hospital admissions (SMR01); and psychiatric hospital admissions (SMR04).Safe Haven, and anonymised prior to release to the research team for analysis via a secure web link.The study was incepted on 1 January 2005, and the BPI-SF, substance use profiles and psychiatric assessment instruments were completed by all patients. Five-year follow-up data spanning 2005–2010 were obtained from the electronic health registers and linked at using the Community Health Index (CHI) number, a unique NHS patient identification code. Data were linked electronically by the Health Informatics Centre (HIC) Services, Dundee, a Scottish government-certified 3033 focusing on the issue of equianalgesic dosing . Buprenorphine was not available for conversion in the equianalgesic calculator so the Monthly Index of Medical Specialities (MIMS) conversion ratio was used, whereby, a multiplication factor of ×80 was applied to buprenorphine doses to identify morphine-equivalent doses.Morphine-equivalent doses were established using an online equianalgesic calculator based on the American Pain Society guidelines and critical review papersonline Supplemental material 1).All anxiolytics prescribed in the present study were of the benzodiazepine class and 98% were diazepam; hence, all doses were converted to diazepam-equivalent doses. A wide range of conversion ratios are documented, and the ratios used in the present study (based on mode average) are detailed in the supplementary material  was used to undertake statistical testing. Chi-square and univariate ANOVA analyses were used to examine group differences (CP→ODD vs ODD→CP) across a number of demographic, substance use, pain-related functioning, psychiatric functioning and general functioning measures. Among demographic characteristics, chi-square was used to examine proportional differences in gender and socioeconomic status. Univariate ANOVA was used to examine differences in age. Among substance use characteristics, chi-square was used to examine proportional differences in any illicit heroin, methadone, opioid analgesic, benzodiazepine and cannabinoid use in the past, as well as across all illicit substance use. Chi-square was also used to examine proportion stabilised in OAT treatment, proportion experienced excessive hyperhidrosis in the past 4 weeks, and prior engagement in IV drug use within the past 4 weeks. Univariate ANOVA was used to assess group differences in mean number of days used in the past 30 days for each substance and mean injecting risk score. Among pain characteristics, chi-square was used to examine proportional differences in multiple sites of pain, pain interference, receipt of prescribed opioid analgesics and the perception that pain problems were taken seriously by the treating physician. Univariate ANOVA was used to assess group differences in mean duration of pain, pain intensity and opioid analgesic dose. Among psychiatric assessment characteristics, chi-square was used to examine proportional differences in meeting clinical thresholds on specific assessment instruments . Univariate ANOVA was used to assess group differences in mean scores on the GHQ-28 subscales  and the CORE-OM subscales . Among medical and psychiatric treatment characteristics, chi-square was used to examine proportional differences in receipt of prescribed medication and inpatient treatment. Univariate ANOVA was used to assess group differences in mean number of hospital admissions.p ⩽ 0.025).Since multiple comparisons can result in Type I errors , the familywise error rate was controlled, using a manual Bonferroni’s correction. The familywise error rate  was divided by the number of tests associated with one single hypothesis to establish the critical value (α) for individual tests. Where the critical value was adjusted, this was recorded in the text or table footnotes. This relates specifically to assessments of patients meeting clinical thresholds on the GHQ-28 and the CORE-OM, since it could be argued that they measure similar constructs. Clinical thresholds associated with the total scores on these instruments provide an indication of psychiatric diagnostic status. They were considered to be a family of tests and, therefore, the alpha was adjusted accordingly .Ethical approval was not required for the present study, since all data were anonymised and accessed via a national n = 174) reported the belief that CP had caused ODD (the CP→ODD group) while the remainder  reported the belief that ODD had caused CP (the ODD→CP group).Of the 615 patients in the NHS Substance Misuse Service, 221 (36%) were excluded due to having no pain, 54 (9%) were excluded due to having pain of less than 12 months duration and 88 (14%) were excluded due to reporting no perceived causal relationship, in either direction, between the onset of CP and ODD. The remaining 252 patients (41% of the entire treatment population) comprised the present study cohort. Just over two-thirds of the study cohort  compared with the CP→ODD group   = 10.034; p = 0.002;p ⩽ 0.025).At study inception, the ODD→CP group was associated with a higher mean score on the Physical Health subscale of the MAP  and on a comparable methadone dose (but were less satisfied than the CP→ODD group with OAT treatment). As also suggested by Manhapra et al., it appears that this group perceives ODD to be their primary problem and, in consequence, a proportion may perceive that further OAT treatment, rather than analgesic treatment, would help to attenuate their problems.Patients in the CP→ODD group reported poorer pain-related health and more frequent illicit use of opioid analgesics. Since analgesic effectiveness is associated with more frequent dosing than is obtained in OAT, more frequent illicit use of opioid analgesics in this group may indicate efforts to control unmanaged pain. Indeed, membership of this group was significantly associated with a longer mean duration of pain and a higher mean intensity of pain. This finding is consistent with the characteristics of CPOD described by Manhapra et al., who found no group differences concerning lifetime mood and anxiety disorders. Higher rates of psychiatric problems are commonly a function of affective distress states associated with opioid withdrawal,35 and, in consequence, the findings of their study may have been ‘diluted’ by the inclusion of patients with other drug and alcohol disorders. Patients in the ODD→CP group were also associated with poorer physical health, a higher number of admissions to general hospitals and a higher mean number of nights spent in inpatient facilities. These findings are contrary to the work of Manhapra et al., who suggest that people with a primary pain problem (i.e. patients with CPOD), rather than a primary opioid use problem, are likely to experience medical and psychiatric instability. They did not, however, characterise opioid-dependent people who subsequently develop pain. It may be that opioid-dependent patients with comorbid CP present with relatively more complex medical and psychiatric complications than those without pain – indeed our previous work has shown this in relation to psychiatric disorders. Future research studies might consider including a third, comparator group – those with opioid use problems and no pain problems.Patients in the ODD→CP group were associated with more psychiatric morbidity, significantly higher psychiatric subscale scores and significantly more nights spent in psychiatric inpatient facilities. This finding is contrary to that of Ilgen et al., examined the relative temporal onset of pain and SUDs. There is an obvious link between exposure to opioids and ODD, and the inclusion in Ilgen’s cohort of patients who had had any SUD  may have resulted in a dilution of any real effect of opioid use disorder on the direction of attribution. Furthermore, in contrast to Ilgen’s approach, the present study adopted a patient-centred approach, in a methadone-maintained sample, asking about patients’ beliefs about the causal relationship in the development of CP and ODD rather than inferring this relationship based on temporal patterns.This is the first study to examine both the patient-attributed causal direction of ODD and CP and its association with health and clinical factors. Ilgen et al. with poorer pain-related health and more frequent use of substances with analgesic properties. Therefore, the principal requirement for this group of patients is the delivery of effective analgesia while minimising harm. This might involve transitioning to non-opioid analgesics or methadone dose titration; however, many patients struggle with this approach, developing greater pain severity and pain-related functional impairment. In this case, an alternative approach might involve opioid substitution with buprenorphine , to minimise the harms associated with methadone. However, it should be noted that there is evidence to suggest that buprenorphine is relatively ineffective at reducing pain intensity in patients with comorbid opioid use disorder. Given that pain appears to be the driver for aberrant behaviours in this group, these patients may find non-pharmacological interventions – such as physical therapy and training in self-management strategies – to be more effective in managing their pain while reducing the risk of exacerbating their OD. It is difficult to comment in detail on the appropriateness of methadone treatment for the ODD→CP group, and future studies should consider comparing functional outcomes in this group with those of ODD patients with no pain. It is clear, however, that patients in this group could benefit from inter-agency approaches involving general and addiction psychiatric services alongside specialist pain services. Our method of directly asking patients about the causal relationship between CP and ODD, while serving its intended purpose in this study, is not recommended for use in clinical practice. Accurately responding to this question demands an understanding of the complexities in the relationship between CP and ODD, complete candour and faultless recall – unrealistic demands to place upon patients. Instead, there may be a valuable role for general practitioners, as the coordinators of medical care, in carefully monitoring disease trajectories as symptoms develop and ensuring that the most appropriate care services are provided.All patients in both of these groups were maintained on methadone, and this may not be the best available treatment for these groups. Certainly, the CP→ODD group appears strikingly similar to the CPOD patients described by Manhapra et al.,This is a novel study that examines clinical characteristics in OAT patients with CP as a function of the causal relationship between the development of these two conditions. The findings suggest that they present as two clinically distinct groups; however, further research is required in this area. Future studies may consider including a third, comparator group comprised of those with ODD and no pain. Furthermore, the present study reported descriptive statistics; however, the use of inferential statistics could facilitate the identification of causal links regarding CP, OD and functional outcomes. In order to direct policy and practice, however, experimental studies are required that can demonstrate the effectiveness of appropriate treatment interventions in each of these clinically distinct patient groups. In addition, patients with severe CP may find it more difficult to access care due to mobility issues or other functional impairments, and this could result in further sample bias. Finally, descriptive statistical analyses are presented in this article; future studies should consider using inferential statistics to facilitate the identification of causal links regarding CP, OD and functional outcomes.The reliance on patients to determine the presence and direction of any causal relationship in the development of CP and ODD could have resulted in a degree of misclassification between groups, since some may have attempted to justify drug use as attempts to bring about analgesia. The stigma associated with opioid misuse – and, more broadly, substance misuse – is culturally pervasive and multifaceted and can, ultimately, result in non-engagement or disengagement from treatment.Two clinically distinct treatment populations were identified based on the causal attribution of these two disorders. Those reporting that CP caused ODD were characterised by poorer pain-related health and more frequent illicit use of opioid analgesics. A higher proportion of those reporting that ODD caused CP was associated with illicit use of methadone, opioid analgesics and cannabinoids and IV drug use; this group also reported more frequent illicit use of heroin and methadone and was associated with poorer general health. In patients with both ODD and CP, establishing whether there is a causal relationship between the two disorders and, if so, identifying the direction of that relationship could help pain services to develop more effective, individualised treatment strategies. For patients reporting that ODD caused CP, this might include inter-agency approaches involving general and addiction psychiatric services alongside specialist pain services. For patients reporting that CP caused ODD, this may include careful monitoring of pain-related health and substance use and the delivery of effective analgesia while minimising harm using techniques such as dose titration, opioid substitution, transitioning to non-opioid analgesics, physical therapy and training in self-management strategies.Click here for additional data file.Supplemental material, sj-pdf-1-bjp-10.1177_20494637211026339 for Opioid dependence disorder and comorbid chronic pain: comparison of groups based on patient-attributed direction of the causal relationship between the two conditions by Cassie Higgins, Blair H Smith and Keith Matthews in British Journal of Pain


We conducted a randomized controlled trial involving adults who needed a cerebrospinal fluid analysis in an emergency department. Patients were randomly assigned to inhale either 50%N2O-O2 or medical air. The primary endpoint, assessed using a numerical scale, was the maximum pain felt by the patient during the procedure and the maximum anxiety and satisfaction as secondary outcomes. Eighty-eight patients were randomized and analyzed (ITT). The maximal pain was 5.0 ± 2.9 for patients receiving air and 4.2 ± 3.0 for patients receiving 50%N2O-O2 . LP-induced anxiety was 4.7 ± 2.8 vs. 3.7 ± 3.7 (p = 0.13), and the proportion of patients with significant anxiety (score ≥ 4/10) was 72.7% vs. 50.0% (p = 0.03). Overall satisfaction was higher among patients receiving 50%N2O-O2 . No serious adverse events were attributable to 50%N2O-O2 inhalation. Although inhalation of 50%N2O-O2 failed to reduce LP-induced pain in an emergency setting, it tended to reduce anxiety and significantly increased patient satisfaction.Lumbar puncture (LP) is stressful and often painful. We evaluated the efficacy of a fixed 50% nitrous oxide–oxygen mixture (50%N Lumbar puncture (LP) was described in the late 19th century . Neverth2O-O2) has been proposed to make this procedure more comfortable for children . The assumption of normality was assessed using the Shapiro–Wilk test. t-test. The result is expressed as the effect-size (ES) and 95% confidence interval (95CI). The relationships between pain, age, and the number of LP attempts were analyzed using correlation coefficients . The results are expressed using correlation coefficients (noted rho) and p-values. The primary endpoint was compared between the randomization groups using Student’s t-test or the Mann–Whitney test if the assumptions to apply the t-test were not met for quantitative variables (such as patient satisfaction). The assumption of homoscedasticity was checked using the Fisher-Snedecor test. The quality of blinding was also evaluated using the Bang blinding index , p = 0.18, respectively), whereas overall satisfaction (< or ≥9) was still associated with active treatment .In multivariable analysis adjusted for age, BMI, the number of LP attempts, and LP duration, significant pain and anxiety were not influenced by use of the active treatment . Among the prespecified outcomes, the quality of blinding, evaluated using the Bang blinding index, was not perfect  were used to treat the 44 patients randomized to inhale 50%N2O-O2 during the whole study. Each bottle was purchased by the hospital pharmacy at a cost of €31.06. We also considered the cost of single-use masks (€0.80), as well as the one-way valve, filters, and pipes (€423.11 for 150 uses). In total, the additional cost of this procedure was a bit less than €8 per patient (including VAT). Regarding the cost of this procedure, seven five-liter bottles , nitrous oxide can expose a patient to several risks. Indeed, methionine synthase antagonism induces vitamin B12 inactivation, which can lead to hematologic and neurologic complications. Such complications are not infrequent in the recreational use of nitrous oxide [2O-O2 mixture is inexpensive compared to many other treatments used in high-income countries, but its cost may still limit its use in countries with a lower standard of living.Moving toward a pain-free hospital is, of course, a laudable objective. However, it remains very difficult in reality, especially in EDs ,40,41,422O-O2 . Of note2O-O2 , infiltrus oxide . Nitrousus oxide . It is a2O-O2 inhalation has a limited effect for the management of immediate pain from lumbar puncture in an ED. However, it appears to be useful in reducing LP-induced anxiety and increases overall patient satisfaction. In conclusion, this trial demonstrates that 50%N