To investigate the association between preoperative dry eye symptoms on postoperative pain and discomfort after photorefractive keratectomy (PRK).  A retrospective case series of 151 consecutive patients, who underwent myopic PRK in both eyes between 5/2016 and 5/2017. Patients with positive dry eye disease (DED) signs on clinical examination or with known DED were excluded. Patients underwent a subjective evaluation for dry eye symptoms using ocular surface disease index (OSDI) and modified standard patient evaluation of eye dryness (SPEED) questionnaires. One day postoperatively, the patients were evaluated again by a questionnaire of pain, discomfort, photophobia, foreign body sensation, satisfaction with vision, and frequency of usage of anesthetic drops. p=0.02). Thirteen patients had a cumulated modified SPEED score >4 (moderate to severe) in comparison to 138 patients with score of 0–4 (non to mild). Patients with moderate to severe preoperative symptoms suffered more pain (p=0.006), photophobia (p=0.005), and epiphora (p=0.03). No statistically significant difference was seen in postoperative subjective visual quality (p=0.82) between the two groups.  Fifty-two patients had any preoperative dry eye symptoms (OSDI score > 0) compared to 99 nonsymptomatic patients (OSDI score of 0). Postoperatively, the symptomatic dry eye patients suffered significantly more pain than the nondry eye patients ( Preoperative dry eye symptoms may be associated with postoperative pain, epiphora, and photophobia and thus influence negatively on patient satisfaction with this procedure. Dry eye disease (DED) is very common ocular condition with a prevalence of 7.4% to 33.7% –5. AccorThe aim of this study is to investigate the effect of preoperative dry eye symptoms on postoperative pain and discomfort during the short-term recovery period after PRK.All data for the study were collected and analyzed in accordance with the policies and procedures of the Institutional Review Board (IRB) of the Barzilai Medical Center and the tenets set forth in the declaration of Helsinki .This retrospective case series included consecutive patients, who underwent myopic PRK in both eyes between 5/2016 and 5/2017 at Care-Vision Laser Centers, Tel-Aviv, Israel. All patients were operated by a single surgeon (IK). Patients under the age of 18 and with history of known DED, previous ocular surgery, suspected keratoconus or keratoconus, active ocular disease, significant refractive media alterations, history of autoimmune disease, collagen disease, and diabetes and pregnant women were excluded from this study.Preoperatively, each patient underwent complete ocular examination including Schirmer's test  and fluoThe epitehlium was removed with application of 20% alcohol for 20 seconds. PRK was performed with the EX500 laser with an optic zone of 6.5–7 mm . Mitomycin C was applied for 20 to 60 seconds according to refraction correction. A soft contact lens was inserted for 4-5 days until full epithelialization.Patients were treated with topical moxifloxacin 0.5% (VIGAMOX) for a week and dexamethasone 0.1% (STERODEX) for a total of one month with gradual tapering down. Patients were provided with one ml of Benoxinate 0.15% and instructed to use in case of unbearable pain during the first 48 hours only. In addition, they were instructed to use oral acetaminophen in case of pain. Artificial tears were given as needed. One day postoperatively, patients were asked to answer a standard “post-op questionnaire.” The questionnaire included grade of pain, photophobia, foreign body sensation, satisfaction with vision, and frequency of usage of anesthetic drops. All questions were with a scale of 1–4 .Patients were divided into two groups according to their OSDI score. The first group had no preoperative DED symptoms (score = 0), and the second group of patients had any preoperative DED symptoms (score > 0). Patients were also divided into two groups according to their modified SPEED score. The first group had non to mild symptoms (score of 0–4), and the second group had moderate to severe symptoms (score > 4).n=15) revealed that for patients without DED symptoms, the mean postoperative pain was 3.7 ± 1.5 and that there was a 2 : 1 ratio of patients without and with DED symptoms and a 20% increase in postoperative pain in patients with DED symptoms. Therefore, with an alpha of 0.05 and a power of 0.80, we calculated that ∼48 patients would be required in the OSDI > 0 group and ∼97 in the OSDI = 0 group.An internal pilot analysis  and analyzed with the SPSS statistical software version 23.0 . For the analysis of continuous data, Student's A total of 151 consecutive patients, with a mean age of 24 ± 6 years, were included in this study. Contact lenses were preoperatively worn by 50.7% of them.p=0.02). The other postoperative symptoms including photophobia, quality of vision, foreign body sensation, epiphora, and number of times of the anesthetic drops were used were not significantly different between the groups (Fifty-two patients had any preoperative dry eye symptoms (OSDI score > 0) compared to 99 nonsymptomatic patients (OSDI score of 0). Symptomatic patients suffered significantly more pain in the first postoperative day than the nonsymptomatic patients (e groups .μm) and postoperative day 1 pain  and a significant negative correlation between refractive error and postoperative day 1 pain . There was no significant difference in mean max ablation depth (μm) between eyes with various pain grading (p=0.04).There was a nonsignificant negative correlation between ablation depth . In addition, postoperative day 1 pain between contact lens wearers (3.67 ± 1.36) and those that did not wear contact lenses (3.71 ± 1.23) before the surgery was similar (p=0.86).There was a similar proportion of contact lens wearers in the OSDI > 0 group (52.9%) and the OSDI = 0 group (49.5%) (p=0.006), more photophobia (p=0.005), and more epiphora (p=0.03) in the first postoperative day than those with non to mild preoperative symptoms. No statistically significant difference was seen in postoperative quality of vision (p=0.82) or foreign body sensation (p=0.47) between the two groups in the first postoperative day (Thirteen patients had a cumulated modified SPEED score >4 (moderate to severe) in comparison to 138 patients with score of 0–4 (non to mild). Patients with moderate to severe preoperative symptoms suffered more pain (tive day .n=25) (p=0.024) and tearing (p=0.046) and to use more the anesthetic drops (p=0.047) in the first postoperative day. Patients that reported suffering from preoperative tearing (n=15) had statistically significant (p=0.02) more pain on the first postoperative day (n=30) suffered more from postoperative foreign body sensation (p=0.019) than those that did not (p=0.031) than those that did not. Patients reporting preoperative eye fatigue (n=33) were more likely to suffer from pain (p=0.019) and photophobia (p=0.005) the first day after the PRK and those reporting preoperative ocular redness (n=11) suffered significantly more from tearing (p=0.039)   were sigtive day . Patient did not . Those rp=0.039) .In this paper, the relationship between having preoperative any dry eye symptoms and post PRK pain, discomfort, epiphora, and quality of vision was examined. It was found that preoperative dry eye symptoms, assessed by the OSDI and modified SPEED questionnaires, without any objective findings, can significantly influence on the first postoperative day discomfort following PRK.To understand how PRK in the presence of DED can accentuate pain, it is important to consider the innervation of the cornea and the perception of pain from the ocular surface. The cornea is mostly innervated by polymodal nociceptors, which are activated by chemical mediators upon corneal injury, heat, and cold. The main neurotransmitters are calcitonin gene related peptide and substance P, that also act as proinflammatory substances, promoting the release of other mediators resulting in “neurogenic inflammation.” Inflammatory mediators from the injured cells induce changes in the ion channel functioning by interacting with the nociceptor ending membrane, resulting in depolarization that increases the nerves excitability. This could explain the increased pain sensation in inflamed tissues. PRK damages the corneal nerve endings that terminate in the anterior stroma and epithelium. This damage may form increased sensory influx to second- and higher-order nociceptive neurons, which result in enhancement of their excitability, hyperalgesia, and allodynia , 23. ChrPrevious studies demonstrated that DED, resulted in decreased corneal sensation, decreased tear secretion, and tear film stability, after PRK , 16. In In meibomian gland dysfunction (MGD), the viscosity of the meibum is increased, possibly due to changes in meibum composition . Stasis Mild DED can result in dry eye symptoms, reflected in a positive OSDI or modified SPEED questionnaires without objective findings such as TBUT and Schirmer's test. Thus, it is sometimes difficult to clinically assess the severity of preoperative DED. In this study, we demonstrated that patients without preoperative clinical findings of DED and without positive dry eye symptoms complains will suffer less postoperative pain, epiphora, and photophobia. On the contrary, patients with mild preoperative dry eye symptoms, even without any objective clinical findings, may suffer more after PRK.Interestingly, in the current study, there was no correlation between ablation depth and postoperative pain. In addition, there was a negative correlation between refractive error and postoperative pain. This contradicts the findings of Garcia et al.  who repoThe main limitations of this study are its retrospective nature and it being subjective as both preoperative dry eye symptoms and postoperative complains were evaluated by questionnaires. An additional limitation is the use of a nonvalidated post PRK pain questionnaire. Also, tear osmolality test and confocal microscopy are not performed routinely in our institution and were not examined in this current study. All patients in this study got both eyes operated at the same day, which may influence pain and discomfort. Last, due to the retrospective nature of this study, we cannot comment on the number of hours passed and the evaluation of pain; patients may have been examined anywhere between 14 hours and 36 hours following surgery in the postoperative day 1 visit.Preoperative dry eye symptoms may influence pain, epiphora, and photophobia after PRK and thus influence negatively on patient satisfaction from this procedure. Preoperative dry eye and blepharitis treatment is recommended for patients with any dry eye symptoms, even without objective findings, prior to PRK.


The objectives of this study were to delineate the clinical-epidemiological profile of patients with neuropathic pain (NP) in the groups of SCD patients, from each of the three questionnaires used DN-4, painDETECT - PDQ, LANSS and to compare these three questionnaires in NP evaluation in SCD carriers. This cross-sectional study evaluated 83 patients with symptomatic SCD, aged 14 years or older. Clinical and laboratory data were extracted from the patients’ charts and from information obtained from the patients during the interview before the application of the questionnaire. The calculations were performed using the statistical software Epi InfoTM 7. Pearson’s correlation coefficient was used to compare the neuropathic pain evaluation scales with the software BioEstat 5.3.The use of two or more questionnaires may increase the suspicion of NP in patients with SCD and, with a confirmed diagnosis, adequate treatments will benefit patients. Sickle cell disease (SCD) is the most prevalent genetic disorder in the world, affecting about 100,000 individuals in the United States of America, or one in 500 black newborns .SCD is characterized by recurring and severe episodes of acute pain due to occlusive vessel crises. Severe acute pain episodes are caused by tissue ischemia, resulting from the microcirculation occlusion . They ocFaced with the constant recurrence of acute pain episodes, there is a possibility for chronic pain (CP) to develop. Despite many studies on CP in adults with SCD in the literature, the underlying mechanisms are still not well understood –10. EvenThe International Association for the Study of Pain in 2011 defined neuropathic pain (NP) as “pain caused by an injury or disease of the somatosensory system” . NP, a sNP is associated with a variety of sensory alterations, e.g., lost or increased sensitivity, reflecting the absence of a standard clinical model in these cases , 17.The neurobiological mechanisms that trigger NP, as well as the best strategies for measuring this kind of pain, are still not well understood, which represents a major problem in clinical practice . The actStudies have shown a prevalence of 20 to 25% of NP in patients with SCD, especially in women and among older patients when compared to younger patients within the samples of these studies , 22, 23.Diagnosing NP is not an easy task, however, the diagnosis is indispensable in order to establish the correct and effective treatment –32. If NSeveral validated instruments are available for assessing NP. The classic DN-4 contains ten items: the first seven, called interview-DN-4, evaluate sensory characteristics, whereas the remaining three items detect signs on physical examination  . A simplOur hypothesis is that associating more than one NP screening questionnaire is fundamental to detect it in SCD patients. Thus, the objectives of this study were to delineate the clinical-epidemiological profile of patients with neuropathic pain in the groups of SCD patients, from each of the three questionnaires used , and to compare these three questionnaires in NP evaluation in SCD carriers.Patients were recruited from an university outpatient clinic, which is a regional reference for SCD treatment. The patients came mostly from the state of Sergipe, but some are from municipalities in the states of Bahia and Alagoas. The three states are in the northeastern region of Brazil. Patients are treated in a standardized manner according to national and international protocols for the use of symptomatic drugs, red blood cell transfusions indication, hydroxyurea and iron chelation therapy.This study was approved by the Human Research Ethics Committee of the Federal University of Sergipe (CAAE: 46774515.0.0000.5546). The Informed Consent Form was signed by the patient or the legal guardian in the case of a minor. All methods were performed in accordance with the relevant guidelines and regulations.This cross-sectional study was conducted between July 2015 and December 2017 and evaluated patients with symptomatic SCD confirmed by hemoglobin electrophoresis with a minimum of 14 years-old which was the lowest age of an individual undergoing NP assessment through PDQ thus the same age was restricted for the other instruments used to avoid discrepancies .The tools used in this study for NP detection were the DN-4, PDQ and LANSS scales –37. The p <  0.05 being considered significant. All calculations were performed using the statistical software Epi InfoTM 7. Pearson’s correlation coefficient was used to compare the neuropathic pain evaluation scales with the software BioEstat 5.3, classifying the correlation as perfect (r = 1), strong (r > 0.75), moderate (r > 0.5), weak (r <  0.5) and non-existent (r = 0). The level of significance for the test was 5%, considering values of p < 0.05.Chi-square or Fisher’s exact test was applied to compare the groups with and without NP as a function of the variables: adolescents (14 to 18 years) versus adults (19 to 34 years), gender and use of hydroxyurea. Average values of hemoglobin, reticulocytes, and age were compared in the groups with and without NP using ANOVA or Kruskal-Wallis tests, with values of The studied population corresponded to 554 individuals with symptomatic SCD. Applying the inclusion criteria (absence of a pain crisis or blood transfusion in the last month and age > 14 years), a sequential sample of 83 patients was obtained. No patient refused to participate, and all of them answered the questionnaires appropriately. The average age was 20.6 years  and 50.6% were male. The rest of the demographics, clinical events, and laboratory parameters are shown in Table All patients reported mild pain in the last month, treated at home with non-opioid analgesics for oral administration according to the protocol of the service, but denied pain crises of a disabling nature or leading to the use of opioid analgesics and / or hospitalization during this period. The most frequent sites of pain in descending order were dorsal /lumbar region (65%), abdomen (10.8%), legs (7.2%), hip (6.0%), head (4.8%), feet , joints (2.4%) and arms (1.2%).p > 0.05; Chi-square).Table p < 0.01; Fisher’s exact test)  Tables  and 3.TaAlthough the frequency of neuropathic pain differed when the three assessment scales were compared, it was possible to detect very similar clinical results in the research with LANSS and DN-4 Table . On the Regarding the comparison between the scales, Pearson’s correlation coefficient showed a statistically significant similarity between the DN-4 and LANSS questionnaires, different from the comparisons of DN-4 and PDQ or LANSS and PDQ, as shown in Table This study identified variable prevalence of NP in patients with SCD after evaluation with the DN-4, LANSS and PDQ scales, as shown in Table It was observed that the group of patients with NP had a higher average age in all three questionnaires, and that the proportion of NP was higher among adults when compared with the group of adolescents Table , which wNo association was found between gender and NP in this study Table , which iPatients with SCD inform that is pain the most frequent uncomfortable symptom . The treThere was no difference between hydroxyurea use and the presence of NP Table , which iAssociated depressive symptoms were detected through a self-report by the patient and no diagnostic questionnaire was used for psychiatric disorders. Even with this limitation, the LANSS questionnaire was able to detect a positive association between depression and the presence of NP Table , whereasThe physical mini-exam of the LANSS and DN-4 aims to complement the rest of the questionnaire to establish evidence of NP, but a complete neurological investigation with a thorough physical examination in NP is essential . AccordiA systematic review reinforced the importance of screening questionnaires for NP detection to avoid false-positive diagnoses . It is kIn addition to negatively impacting on the quality of life and psychological well-being, NP it interferes on sleep quality and activities of daily living since. Sensations as loss or reduction of sensibility, shock-type pain, hyperalgesia or allodynia will accompany patients throughout life and may be worse if the trigger of the nerve damage that caused this chronic pain has not been controlled independent of the underlying disease. In the cases of SCD these patients still coexist with another pain type of acute and recurrent character that also interferes enough in the quality of life of these individuals, limiting them to each day , 41, 42.The limitation of this study is the cross-sectional design. So prospective studies will be required to verify if there is a cause-effect relationship between SCD and NP.Therefore, it is concluded that it was possible to identify frequencies of 19.3, 26.5 and 32.5% of patients with NP through the PDQ, LANSS and DN-4 scales, respectively, affecting adults more frequently. Using more than one NP evaluation scale amplifies the detection rate. Sensory investigation through directed physical examination increases the identification capacity of NP patients even in the absence of suggestive anamnesis. None of the patients identified had any type of NP treatment. Thus, the use of questionnaires may increase the suspicion of NP in patients with SCD and, with a confirmed diagnosis, adequate treatments will benefit the patients.


Fibromyalgia (FM) is one of the most frequent generalized pain disorders with poorly understood neurobiological mechanisms. This condition accounts for an enormous proportion of healthcare costs. Despite extensive research, the etiology of FM is unknown and thus, there is no disease modifying therapy available for this condition. We show that most  patients with FM belong to a distinct population that can be segregated from a control group by their glycated hemoglobin A1c (HbA1c) levels, a surrogate marker of insulin resistance (IR). This was demonstrated by analyzing the data after introducing an age stratification correction into a linear regression model. This strategy showed highly significant differences between FM patients and control subjects . A subgroup of patients meeting criteria for pre-diabetes or diabetes  who had undergone treatment with metformin showed dramatic improvements of their widespread myofascial pain, as shown by their scores using a pre and post-treatment numerical pain rating scale (NPRS) for evaluation. Although preliminary, these findings suggest a pathogenetic relationship between FM and IR, which may lead to a radical paradigm shift in the management of this disorder. Fibromyalgia (FM) is one of the most frequent generalized pain disorders with poorly understood neurobiological mechanisms. In the general population, the estimated global prevalence of FM is 2.7% with a 3 to 1 female to male ratio [Patients afflicted with FM have chronic widespread pain and protean somatic symptoms including fatigue, nonrestorative sleep, gastrointestinal complaints and problems of cognition and mood .The global economic impact of FM is enormous. In the United States alone, the healthcare cost is around $100 billion/year; comparable to reports in European countries . Due to FM is considered a central sensitivity pain disorder characterized by abnormal processing of nociceptive stimuli . In addiMany hypotheses have been advanced to explain the extensive array of symptoms including inherited abnormalities , dysfuncPrior observations indicate that IR causes dysfunctions in the brain microvasculature leading to focal cerebral hypoperfusion . Since sIn order to supplement this finding, we also reviewed the evolution of the pain scores of patients with FM who had had their IR treated pharmacologically. This subgroup of patients reported dramatic improvements of their myofascial pain after treatment with metformin.This evidence, although preliminary, suggests a pathogenetic relationship between FM and IR, which may lead to a paradigm shift in the management of this disorder.We identified 23 patients from a retrospective chart review who were referrals to a subspecialty pain medicine clinic for the treatment of widespread myofascial pain. All patients had met the 1990  as well Since there is a known association between small fiber neuropathy and FM , 18, manThe HbA1c values from 23 patients with FM  were compared with the HbA1c means of two independent control populations. One was a non-diabetic population with normal glucose tolerance  for the ages stated in the graph . The secBecause peripheral neuropathies  that are associated with IR may start at very early stages of pre-diabetes, there is a growing trend among experts to begin early pharmacological interventions to correct this abnormality, particularly when IR is associated with neuropathy or other risk factors . FollowiIn order to characterize the variation contributed from the patients, sets of simulated HbA1c data were generated to emulate the populations which were the source of the HbA1c values in the controls. Separately for FOS NGT and NHANES nondiabetic, over the bounded age range from 40 to 69, the tabled values of N, mean, and standard error of each age group were used to estimate the corresponding standard deviation (estimating standard deviation for each age group as the product of the standard error and square root of N). A corresponding simulated source population for the data was generated for each centered age as a set of random normally distributed values with the tabled Ns and means and the calculated standard deviation . Means aThis study has been determined by an Investigational Review Board  to meet the exempt criteria according to the Code of Federal Regulations governing the performance of this research.From all analytes reviewed, only the HbA1c levels segregated patients with FM from control subjects . DespiteNPRS for patients who were treated with metformin are reported in graphic form in Pain scores differed significantly per the sign test among all groups , with p <0.0001 in each pairwise comparison, as illustrated in HbA1c values in 23 patients with FM  were compared with the means of two control populations as described in the text. 1-A non-diabetic population with normal glucose tolerance (obtained from the Framingham Offspring Study) and 2-A nondiabetic population from the NHANES data set. Regression lines are shown with shaded 95% confidence regions. FOS NGT and NHANES nondiabetic HbA1c values include scatterplots of published mean values for each age region, while HbA1c results from patients with FM include a scatterplot of measures from individual patients . The regression estimates that HbA1c values in patients with FM average 0.59 +/- 0.1 (mean +/-SE) units higher than FOS NGT (p<0.001), and 0.39 units higher than the NHANES nondiabetic values, p = 0.0002. Because of overlapping values, not all individual patients can be plotted in the graph. For this reason, individual data values for each patient are provided in only to metformin and not to ST with NSRIs or membrane stabilizing agents. Importantly, there was a long-term retention of the analgesic effect of metformin as noted in The subgroup of patients who had undergone pharmacological treatment of IR with metformin, in combination with the ST, experienced a dramatic decrease in the pain scores . ResponsI-NPRS: Initial pain scores at presentation. 2-ST-NPRS: Numerical pain scores after standard treatment . M-NPRS: Numerical pain scores after addition of metformin. Pain scores are the average of the worse pain experienced in the 7 days prior to the encounter. All pairwise differences among the groups were significant, p<0.0001, per the sign test and following adjustment for multiple comparisons, as shown in The results showed a highly significant association between FM and HbA1c levels. Stratification of the values in an age continuum, showed a clear-cut difference between the patients and the control groups. As can be visually appreciated in the graph in HbA1c does not directly measure IR; however, it is widely recognized as a surrogate marker for this abnormality . Non-diaIn view of the substantive research efforts involved in FM, including those from the pharmaceutical industry, we were puzzled that prior investigations had overlooked these simple findings. The main reason for this oversight is that many patients with FM show HbA1c values currently considered to be within the normal range; however, this is the first study to analyze the data in an age-stratified manner. This is important, considering the effect of aging on HbA1c levels . TherefoIt is important to give credit to the effort of other investigators who have also sought this association. Tishler et al  found thFava et al  showed tindependent of its action on IR [Based on our data, we would like to propose that IR is pathogenetically linked to FM. However, there are several caveats to our proposition which must be carefully considered in the design of future clinical trials attempting to confirm this hypothesis. One is the limitation intrinsic to retrospective cross-sectional studies. Because IR and FM were simultaneously assessed, evidence for causality is more difficult to establish in the absence of a temporal relationship. Secondly, patients with FM are commonly overweight or obese , factorson on IR , 31. Meton on IR –34 whichon on IR –34. In fon on IR , 36. In on on IR  and relaon on IR  could noDespite all these caveats, this initial report prompts us to seek answers to a challenging set of questions generated by this hypothesis. It would be unlikely for a placebo type of effect alone to result in the impressive degree of long-lasting pain improvement experienced by the patients who received the drug combination (metformin plus ST). Remarkably, “non-responders” were conspicuously absent in our patient’s sample; such an unusual and atypically low “number needed to treat” (NNT) would be more in line with a disease modifying therapy.In conclusion, IR is being increasingly associated with a broad number of neurological disorders –24 and F


During Voltaire’s time, his famous bon mot was largely correct. However, today, things are very different, and in the spirit of this Special Issue on a critical assessment of alternative medicine, I argue that it ought to be re-phrased as follows: “The art of alternative medicine consists in amusing the patient, while medics cure the disease”.To illustrate this point, I shall use this editorial to tell the tale of a patient seeking care from a range of clinicians. The story is fictitious but nevertheless based on many real experiences of a similar nature.Tom is in his mid-50s, happily married, mildly over-weight and under plenty of stress. In addition to having a demanding job, he has recently moved home. As a consequence of lots of heavy lifting, his body aches. He had previous episodes of back trouble and re-starts the exercises a physiotherapist once taught him. A few days later, the back-pain has improved, and most other pains have subsided as well. Yet a dull and nagging pain around his left shoulder and upper arm persists.He is tempted to see his general practitioner (GP), but his wife is fiercely alternative. She was also the one who dissuaded Tom from taking statins for his high cholesterol and put him on garlic pills instead. Now she gives Tom a bottle of her Bach flower remedies, but after a week of taking it, Tom’s condition is unchanged. His wife therefore persuades him to consult alternative practitioners for his persistent ‘shoulder problem’. Thus, he sees a succession of her favourite clinicians.The chiropractor examines Tom’s spine and diagnoses subluxations to be the root cause of his problem. Tom thus receives a series of spinal manipulations and feels a little improved each time. However, he is disappointed that the pain in the left shoulder and arm returns. His wife therefore makes another appointment for him.The energy healer diagnoses a problem with Tom’s vital energy as the root cause of his persistent pain. Tom thus receives a series of healing sessions and feels a little improved each time. However, he is disappointed that the pain in the left shoulder and arm returns. His wife therefore makes another appointment for him.The reflexologist examines Tom’s foot and diagnoses knots on the sole of his foot as causing energy blockages which are the root cause of his problem. Tom thus receives a series of most agreeable foot massages and feels a little improved each time. However, he is disappointed that the pain in the left shoulder and arm returns. His wife therefore makes another appointment for him.The acupuncturist examines Tom’s pulse and tongue and diagnoses a chi deficiency to be the root cause of his problem. Tom thus receives a series of acupuncture treatments and feels a little improved each time. However, he is disappointed that the pain in the left shoulder and arm returns. His wife therefore makes another appointment for him.The naturopath examines Tom and diagnoses some form of auto-intoxication as the root cause of his problem. Tom thus receives a full program of detox and feels a little improved each time. However, he is disappointed that the pain in the left shoulder and arm returns. His wife therefore makes another appointment for him.The homeopath takes a long and detailed history and diagnoses a problem with Tom’s vital force to be the root cause of his pain. Tom thus receives a homeopathic remedy tailor-made for his needs and feels a little improved after taking it for a few days. However, he is disappointed that the pain in the left shoulder and arm returns. His wife therefore tries to make another appointment for him.By this time, Tom had enough. Despite all these treatments, his pain has not substantially improved; on the contrary, he is increasingly feeling desperate and unwell. At the risk of a marital dispute, he consults his GP. The doctor looks up Tom’s history, asks a few questions, conducts a brief physical examination, and arranges for Tom to see a specialist. A cardiologist diagnoses Tom to suffer from coronary heart disease due to a stenosis in one of his coronary arteries. She explains that Tom’s dull pain in the left shoulder and arm is a rather typical symptom of this condition.Tom has a stent put into the affected coronary artery, receives several medications for lowering his cholesterol and blood pressure, and is told to take up regular exercise, lose weight and make several other changes to his life-style. Tom’s wife is instructed in no uncertain terms to stop dissuading her husband from taking his prescribed medicines, and the couple are both sent to see a dietician who offers advice and recommends a course on healthy cooking. Nobody leaves any doubt that not following this complex (and holistic) package of treatments and advice would be a serious risk to Tom’s life.It has taken a while, but finally Tom is pain-free. More importantly, his prognosis has dramatically improved. The team who now looks after him have no doubt that a major heart attack had been imminent, and Tom could easily have died had he continued to listen to the advice of multiple non-medically trained clinicians.The root cause of his condition was misdiagnosed by all of them. In fact, the root cause was the atherosclerotic degeneration in his arteries. Even if the atherosclerotic process cannot be halted completely, it can be significantly slowed down such that Tom can live a full life.Alternative practitioners are often full of good intentions;They are often very good at pampering their patients;This may contribute to some perceived clinical improvements;In turn, this perceived benefit can motivate patients to continue their treatment despite residual symptoms;Alternative practitioner’s claims about ‘root causes’ and holistic care are usually pure nonsense;Their pampering may be agreeable, but it can undoubtedly cost lives.My conclusion and advice based on this invented tale  is this:We live in a time where alternative medicine is being seen as something harmless, and it is true that most treatments are not only safe but also quite pleasant. As we will discuss in this theme issue in some detail, this perception is perhaps not entirely correct and can even endanger the lives of patients.


Patients feel uncomfortable with cervical manipulation, uterine distension and stimulation of peritoneum during hysterosalpingography (HSG) and experience lower abdominal pain during and after the procedure. Pain during the procedure has a negative effect on the adaptation of patients to treatment and physicians are trying to overcome this unpleasant situation. Therefore, the aim of this study was to compare the effect of midazolam and dexmedetomidine on reducing pain and spasm of fallopian tubes during and after HSG procedure in women with infertility. In a double-blind randomized controlled trial, 102 patients were randomly divided into two groups, midazolam and dexmedetomidine. The pain was recorded during injection and immediately after injection and 30 minutes after HSG, and then the complications of injection were recorded. Finally, the data were analyzed using SPSS version 20. Based on the results presented herein, no significant difference was found between the two groups in terms of vasovagal reaction, spasticity of the tube and the side of the spastic tube and uterine cavity anomalies (p <0.05). However, the pain showed a significant difference between the two groups during the injection, immediately or at 30 minutes after the procedure (p = 0.0001). The pain in the midazolam group was less than that of dexmedetomidine. Furthermore, there was no significant difference between the two groups regarding spasticity (p <0.05). There is a benefit in terms of pain reduction with the use of dexmedetomidine when comparing with midazolam injection. However, dexmedetomidine does not cause side effects in patients and can be used to reduce pain during injection. National Institute for Health and Care Excellence (NICE) recommended HSG guidelines as a useful approach for screening for blocked fallopian tubes [. Although this procedure is non-invasive, which does not require cervical dilatation or anesthesia, however, the patients expressed discomfort because of manipulation of the cervix , uterine distention and stimulation of peritoneum, where they experienced lower abdominal pain during and after the procedure. Pain during the procedure has a negative impact on the adaptation of patients to the treatment and physicians are trying to overcome this unpleasant situation [non-opioid analgesics versus placebo [non-opioid analgesics [, as well as local anesthetics and placebo [spasm of the fallopian tubes during HSG, and most studies have been conducted to reduce the pain of these patients during the procedure. The effect of dexmedetomidine and midazolam on pain and spasm of fallopian tubes has not been studied so far. Therefore, the main aim of this study was to determine the effect of dexmedetomidine and midazolam on pain and spasm of fallopian tubes during and after HSG in women with infertility.Infertility is one of the most common problems in women’s medicine. This complication involves a heterogeneous group of patients and infertility-related assessments require special attention to determine the cause of infertility. Hysterosalpingography (HSG) has become a commonly performed diagnostic method for assessing the inside of the uterine cavity and fallopian tubes . Due to an tubes . Althougituation . Many st placebo , and opialgesics , as well placebo -8. Howevdouble-blind randomized controlled trial was performed on patients undergoing HSG, referring to the radiology clinic in Arak, Iran. In this study, 102 patients were randomly divided into two groups, midazolam and dexmedetomidine, using hypercube sampling.This menstrual cycle to participate in this study. The patient was placed in a supine position after being prepared on the bed and peripheral venous catheter 20 was placed into a peripheral vein for all of them. In group 1, 1μg/kg of dexmedetomidine  was injected 3-4 minutes before the procedure; subjects in group 1 then received an infusion of 0.5mg/kg dexmedetomidine. The second group received infusion doses of midazolam, 0.4 mg/kg (volume: 3 ml) 3-4 minutes before the procedure. Normal saline  was infused into patients in the second group. After achieving target sedation of grade 3 on the Ramsay scale, the process was started and the patient was placed in a lithotomy position. Afterward, a sterile speculum was placed inside the vagina. After the cervical vision, a betadine solution was used for scrubbing of area. The anterior or posterior edges of the cervix were then taken by the tenaculum and the cannula of the hysterosalpingogram was entered in the cervical canal. The speculum was then removed and 5 cc contrast agent was injected. At this time, the patient was asked to determine their pain intensity using the visual analog scale. The presence or absence of spasm of fallopian tubes was determined at this stage. In the absence of contrast in the uterine tubes, spasticity was detected after the first and second injection. However, if the contrast agent did not pass through the uterine tubes, after repeated injections and patient relaxation, fallopian tube obstruction was revealed and the patient was excluded from the study.Inclusion criteria included women with infertility, aged 20-45 years, having informed consent, contraindication for the use of dexmedetomidine, contraindication of the use of midazolam, no known uterine malignancy, lack of vaginal bleeding, no history of cervical surgery, no PID, absence of painkiller use before HSG and fallopian tube obstruction. Exclusion criteria included HSG duration greater than 45 minutes and presence of unstable hemodynamic symptoms during HSG. The method was explained to the selected patients and they were consciously entered into the study after obtaining written consent. All women were placed in the follicular phase of the At the end of the procedure, all instruments were removed, and the patients were monitored for half an hour in the clinic. The patients were also asked about pain after HSG thirty minutes after the completion of work. In addition, patients were also questioned about vasovagal symptoms including nausea, vomiting, sweating, weakness, hypotension, and bradycardia 30 minutes after the procedure. Data were then analyzed by SPSS software v 20.In the midazolam group, 57 patients were examined, of which six were excluded from the study due to tube obstruction, and 55 patients in the dexmedetomidine group were examined, of which four were also excluded. One patient was excluded from the study due to hemodynamic impairment and pressure drop and the other three were excluded because of the tube obstruction. Moreover, the minimum age was recorded as 19 years and the maximum age was 43 years. The mean age of patients was also determined to be 29.15 ± 5.24 years. Duration of infertility in the dexmedetomidine group was 25.64 ± 19.99 months and this period was also found to be 26.09 ± 23.66 months for midazolam group, where no significant difference was found between the two groups (p = 0.916). According to the results, there was no significant difference between the two groups in terms of age (p = 0.98). In addition, there was no significant difference between the two groups regarding parity, dysmenorrhea, history of dyspareunia, history of HSG and history of endometrial biopsy (p <0.05). Furthermore, no significant difference was found between the two groups in the duration of HSG (p = 0.878). Based on the data presented herein, two groups did not show a significant difference in terms of vasovagal reaction and uterine cavity anomalies (p <0.05). Additionally, there was no significant difference between the two groups regarding spasticity of the tube (p <0.05),  and 2.As indicated in In addition, no significant difference was found between the two groups regarding the number of injection (p = 0.747).Infertility is a complex situation that affects people’s lives in many ways . InfertiIn most women, this pain has a negative effect on HSG in patients, so specialists have taken different drug interventions to reduce pain in these patients -14. In tThe findings of this study demonstrated significant difference between the two groups regarding the duration of infertility. In addition, no significant difference was found between the two groups of patients in terms of parity, dysmenorrhea, history of dyspareunia, history of HSG, and history of endometrial biopsy. There was no significant difference between two groups in terms of vasovagal reaction and anomaly of the cavity, and no significant difference was revealed in spasticity of the tube. Based on our findings, pain at all times exhibited a significant difference between the two groups (p < 0.05). The pain in the midazolam group was lower as compared to the dexmedetomidine group. No significant difference was found between the two groups regarding the duration of HSG and the frequency of injections.To the best of our knowledge, there is no similar study like our survey. Therefore, we try to compare studies that focused on reducing the pain during and after HSG.Hassa et al., evaluated the effects of oral nonsteroidal anti-inflammatory drugs (NSAIDs) and aginal misoprostol for decreasing pain during, and 30 minutes after, HSG. They demonstrated no benefit in terms of pain reduction using oral nonsteroidal pain during, and 30 minutes after, HSG procedure, while the use of NSAIDs can relieve pain 30 minutes after HSG procedure . AlthougAnother study assessed the effect of 5% lidocaine 25 mg-prilocaine 25 mg/g cream for decreasing pain during HSG. This study showed that endocervical and exocervical topical use of the EMLA 10 minutes before HSG is capable of decreasing the pain during manipulation of the cervix with tenaculum and cannula, but had no effect on the pain during the injection of contrast .pain relief during the HSG as compared to oral naproxen [Gupta et al. in 2007 compared the effect of oral naproxen with intrauterine instillation of 1% lignocaine in relieving the pain caused by HSG procedure in women with infertility. This study revealed that intrauterine application of lignocaine was not capable of showing effective levels of naproxen .In a study by Elson and Ridley in 2000, the effect of paracetamol as a prophylactic pain reliever for HSG in the UK was evaluated. This study reported that paracetamol is not effective in relieving pain caused by the HSG procedure .In the current study, dexmedetomidine and midazolam were capable of reducing pain, but pain reduction after HSG was less in the midazolam group. Spasm did not differ between the two groups and the complications were similar in two groups.There is a favorable effect in terms of pain reduction with the application of dexmedetomidine during HSG or at 30 minutes after performing HSG as compared to the midazolam group. This is despite the fact that dexmedetomidine does not cause side effects in patients and can be used to reduce pain during injection. On the other hand, spasms were similar in two groups.Deputy of Research and Technology of Arak University of Medical Sciences.This thesis is approved at Arak University of Medical Sciences (code IR.ARAKMU.REC.1396.). It also has a registration code at the Iranian Center for Clinical Trials (IRCT2017081520258N57). We are grateful for the material and spiritual contributions of Research Development Center of Valiasr Hospital and The authors confirm that there are no conflicts of interest.


The visual analogue scale (VAS) was used; pain scores were measured four times: during local anesthesia, probe insertion, sampling procedures, and at 15 min post procedures. No significant differences were observed in VAS scores during local anesthesia  or during probe insertion . Similarly, no differences in VAS scores were detected during the sampling procedures  and at 15 min post procedures . No major complications were noted in either group. Both PPB and PNB are comparably effective and safe methods for PBx related pain relief, and PPB is not superior to PNB. Local anesthetic method could be selected based on the preference and skill of the operator.We evaluated whether pelvic plexus block (PPB) is superior to periprostatic nerve block (PNB) for pain control during transrectal ultrasonography (TRUS)-guided prostate biopsy (PBx). A prospective, double-blind, randomized, controlled study was performed at a single center; 46 patients were enrolled and randomly allocated into two groups: PPB ( Prostate cancer (PCa) is the most frequently occurring malignancy in men worldwide, with approximately 1.1 million new cases diagnosed each year . NotablyRecently, various local anesthetic methods have been developed to reduce PBx-related pain. These involve multiple types of anesthetic agents and sites of injection, and when used either alone or in combination, most were found to be effective for control of PBx-related pain . During Pelvic plexus block (PPB), which involves injecting lidocaine directly lateral to the tip of the seminal vesicles, was first described by Wu et al. . Becausehttp://clinicaltrials.gov . This prospective, double-blind, randomized, controlled study was performed at one institution  from September 2018 to February 2019. Ethical approval was obtained from the Institutional Ethical Committee , and the study is registered at Patients with an abnormal prostate finding during digital rectal examination (DRE), a serum prostate-specific antigen (PSA) level >2.5 ng/mL, and/or an abnormal lesion detected with TRUS were included in this study. Those under 50 years of age or with a history of previous TRUS-guided biopsy, chronic prostatitis/pelvic pain, neurological conditions , bleeding diathesis, anticoagulation/antiplatelet therapy, active urinary tract infection, hemorrhoids/anal fissure/anal fistula, or a known allergy to lidocaine were excluded from the study. Before the biopsy procedure, patients with active urinary tract infection and prostatitis were excluded by investigation of current symptoms and past history and urine analysis. Written informed consent was obtained from all patients prior to study enrollment.Using pain scores reported in the literature , we estiEnrolled patients were randomly allocated by computer randomization into the PPB and PNB groups. The former received PPB and the latter received PNB. All patients took levofloxacin  prior to the procedure, for a total of five days, and received intravenous third-generation cephalosporine on the day of the procedure, according to the institutional protocol. A cleansing enema was also performed on the morning of biopsy. All block procedures were performed by a single well-experienced urologist who was accustomed with five years of experience with performing the block procedure. Another single urologist, with more than seven years of prostate biopsy experience, conducted all the biopsy procedures using a BK 3000 scanner , with a 4- to 14-MHz endorectal triplane transducer. During the procedure, patients were placed in a right lateral decubitus position. EMLA cream  was applied first around the anal ring and 10 mL 2% lignocaine jelly was instilled into rectum 10 min before the introduction of the TRUS probe. Nerve block (either PPB or PNB), with 2.5 mL 2% lidocaine, was injected into both sides of the prostate , using a 21 G, 15 cm Chiba needle . In the PPB group, lidocaine injections were administered to the pelvic neurovascular plexus, located at the end of the seminal vesicle, under Doppler-guided ultrasound, on each side ,12,13,14All study participants were blinded to their treatment group assignment, and the urologist who conducted the biopsy procedures was blinded as to the type of nerve block given. A physician’s assistant, who was also not aware of the type of nerve block administered, explained the visual analog scale (VAS) to the participants and requested they rate their degree of pain or discomfort from 0 to 10 at four time points: (1) VAS-1, during the local anesthesia procedure, (2) VAS-2, during ultrasound probe insertion, (3) VAS-3, during the sampling procedure, and (4) VAS-4, 15 min after finishing all procedures. In addition, the physician’s assistant recorded the time it took to complete all procedures. The patients recorded VAS scores themselves, without assistance. The patients were observed for 4 h after the procedures and were counseled about the possibilities of mild hematuria, self-limiting rectal bleeding, mild fever, and/or hematospermia. They were advised to go to the emergency room if they experienced a high fever, syncope, massive hematuria, or urinary retention. All patients were reviewed again after one week to monitor for any late complications.p-values were calculated using SPSS version 23 , and p < 0.05 was considered statistically significant. The primary outcome of the present study was VAS scores at the time of biopsy. Pain scores  and the time to complete all procedures were compared between the two groups using the Mann–Whitney test. n = 46). These 46 patients were randomized into two groups, PPB (n = 23) and PNB (n = 23).Overall, 53 patients were assessed for eligibility and provided consent to be included in the study. Of these, seven patients did not meet the inclusion criteria : four hap = 0.154) (p = 0.537). Mean pain scores at ultrasound probe insertion after anesthetic procedure (VAS-2) were 2.83 ± 2.21 for the PPB group and 2.39 ± 1.90 for the PNB group (p = 0.569). There were also no differences in mean pain scores during the sampling procedure , and for those measured 15 min after finishing all procedures . There were no significant differences in age, prostate volume, and serum PSA between the two treatment groups. The total time for all procedure was 12.52 ± 3.39 min for the PPB group and 13.78 ± 2.91 min for the PNB group (= 0.154) . Table 2There were no major complications, including urinary tract infection, sepsis, or significant rectal or urethral bleeding, reported by any of the patients. Pain during PBx is caused by the introduction and manipulation of the ultrasound probe into the anal canal and rectum, as well as by penetration of the needle into the prostate capsule, which is rich in autonomic sympathetic and parasympathetic fibers ,17. In gPPB was first described as an alternative to PNB by Wu et al.  in 2001 Recent meta-analysis by Li et al.  found thThe characteristics and outcomes of this present study, as compared to previously published studies, are summarized in We conducted a study of 46 patients; 23 across two groups. The total number of participants may be considered too small when compared to the previous studies ,13,14. HNotably, all studies being compared were designed as double-blind investigations; however, we speculate that the current study may have less bias in the blinding step, due to the fact that clinicians performing the anesthesia, the biopsy procedure, and the access of the VAS scores were different and the physicians performing PBx and accessing the VAS score were blinded to the type of local anesthetic method. Other differences include the fact that Akpinar et al.  performeWe note, however, that the present study was not designed to evaluate the pain scores based on the site of biopsy, and therefore it remains unclear whether PPB may help in controlling pain associated with apex biopsies, due to the blocking of the anterior nerve fibers that might be missed by PNB. Further studies will thus be needed to clarify this issue. Lastly, VAS is widely used for epidemiological and clinical studies, and its strengths and weaknesses are well appreciated . In partWe found that despite the theoretical advantage of PPB, this technique did not show superiority for PBx-related pain control as compared to PNB. Thus, our data suggest that both PPB and PNB are comparably effective and safe methods for pain control in patients undergoing PBx, and as such, the local anesthetic method utilized in this procedure could be selected based on the preference and skill of the operator.


OnobotulintoxinA (OBT-A) is a treatment option for Chronic Migraine (CM). It works on central sensitization and pain but its mode of action is still unknown. To observe how OBT-A treatment works on single migraine attacks, this paper covers an over-6-month observation period through self-reported smartphone application data. This was an observational, open-label cohort study conducted on 34 CM patients under OBT-A treatment, selected between December 2016 and December 2017, who agreed to download a smartphone headache diary application (Aid Diary) according to the study instructions. The analysis was conducted using the smartphone application data reports on allodynia, intensity and extension of pain, and vegetative symptoms. We analysed a total of 707 records of single migraine attacks reported by compliant users (n = 34) in real-time. OBT-A significantly reduced allodynia, the number of vegetative symptoms, pain extension and intensity in single migraine attacks. Pain intensity was correlated with pain extension. In single migraine attacks, OBT-A improved symptoms of central sensitization. This action could be exerted by modulating nociceptive transmission and reducing the burden of single migraine episodes and improving the overall quality of life. Chronic Migraine (CM) is an invalidating disease caused by frequently recurrent migraine attacks and pain persistence between migraine days. Central sensitization facilitates pain persistence, leading to functional changes within the nociceptive trigeminal caudal and cervical system . The effIn a more recent study, we evaluated the long-term effect of OBT-A in CM and observed a reduction of allodynia and global burden of migraine .The knowledge of the clinical features of migraine attacks is mainly based on retrospective studies. In the current scientific literature, no study analyzed the short-term effects of OBT-A single migraine attack features through mobile phone application reports. The mobile phone app could be a useful tool to extemporarily record migraine features. In today’s digital environment, individuals are increasingly using apps to regularly record pain, nutrition, and various medical information .Here we present an open-label six-months-observational study, based on reports of single migraine attacks from real-world CM patients using a self-reported smartphone application, the Aid Diary. Specific aims of the study were the live detection of single migraine attack characteristics, such as pain intensity, allodynia, and pain extension, just to better understand the mode of action of OBT-A on central sensitization symptoms and single migraine attack features.Sample Description: The study sample included 707 migraine records  from 34 users who satisfied the inclusion criteria for the study, were compliant with given instructions and received two OBT-A treatments during six months.All included records satisfied the features of migraine without aura ,11.A summary of demographics and migraine characteristics of the study sample is shown in p < 0.0001; Bonferroni test T0 vs. T1 p < 0.0001; T0 vs. T2 p <0.0001; T1 vs. T2 p < 0.012). No patient reported relevant side effects. Two patients complained about slight neck pain after the first cycle of OBT-A injections.The number of headache episodes, resulting from the paper diary, progressively decreased at T1 and T2 compared to T0  enrolled patients dropped out during a monitoring phase sometimes due to technical reasons related to the updates required to have the application properly working. Secondly, patient subjective judgment about the type of headache to be reported—e.g., migraine or tension-type—could be mistaken. However, the diagnosis of chronic migraine is based on the subjective statement of patients about the number of migraine or tension-type episodes ,11 The dIn summary, the present study provided evidence for the first time about the change of single migraine attack features after OBT-A injections. Taking into account the above-described limitations, the OBT-A effect on migraine intensity, pain diffusion, and vegetative symptoms confirms a global modulatory action on the strength of trigeminal activation. Another potential value of the study could be the reliability of the smartphone app, which deserves further upgrades for the final confirmation of its value in the clinical assessment of migraine. These applications would be potentially useful for patients, their caregivers, or physicians to improve the management of the disease, but also for the wider scientific community to increase the knowledge about the way of action of treatments on acute migraine features.This was an observational, open-label, cohort study conducted in accordance with the principles of the Helsinki Declaration. The study included 57 CM patients that spontaneously came to San Giovanni Rotondo Casa Sollievo della Sofferenza Hospital  between December 2016 and December 2017, agreed to OBT-A treatment  and to be enrolled in our study conducted through a smartphone headache diary application. The Aid Diary was specifically created to capture the extempore details regarding clinical features of migraine by a consequential series of questionnaires.Neurologists with experience in headache management selected CM patients for OBT-A treatment. CM patients were diagnosed according to the most recent classifications ,11. The In line with the Italian Public Health System rules, patients were treated with OBT-A after at least one failed preventive treatment, among those reported by the Italian guidelines . In someAll patients received a paper diary and a smartphone application headache diary at the time of visit booking, before the first session of OBT-A treatment. Users were instructed to recognize migraine characteristics, reporting all headache attacks on their paper diary and only migraine attacks on smartphone application before taking symptomatic therapy with triptans or pain-reducing drugs. Patients were also instructed to fill out both headache diaries 30 days before the day of first OBT-A treatment; moreover, they were instructed to follow the directions of the app minutely, not to skip any questionnaires nor to miss any information.We included in the present study the patients who received at least two OBT-A treatment cycles during the six months. Moreover, we included into the data analysis only compliant patients, who completed the electronic diaries reporting the days of migraine attacks with relative features and symptoms.All patients signed informed consent for the inclusion of their clinical and demographic data in the observational study, with respect of their privacy and the treatment of personal anonymized data. The study was approved by the local Ethic Committee of Bari-Policlinico General Hospital. The approval code: 7/3423.Considering the observational nature of the study, we did not preliminarily calculate the sample size.http://www.terin.it/) It was built to be easy to use, with an obligatory sequence of questionnaires to tick in order to send a complete report; the questionnaires presented in order are: Visual Analogue Scale (VAS) for pain  that allowed us to view all the reports and related items in real-time. This virtual platform shows the individual reports and graphs of any questionnaires . ,3. We usFor the present analysis, we considered data collected at baseline T0 (30 days before first injection session), T1 (records in the 90 days following first OBT-A treatment), and T2 (records in the 90 days following second OBT-A treatment session).For the aim of this study, we entered the data from single migraine attacks into an SPSS database, as variables of univariate ANOVA to be compared among the T0, T1 and T2 conditions. The post-hoc Bonferroni Test was computed.The variables for ANOVA analysis were single attacks’ number of allodynia symptoms, the topographic distribution of pain with the total number of coordinates, number of vegetative symptoms, and subjective pain intensity as measured by a 0–10 numerical scale. The frequency of headache, detected by paper diaries, was compared among T0, T1, and T2 conditions, using the repetitive measure ANOVA and single contrasts computation.The Pearson correlation test was used to measure the correlation between the different migraine attack features.For statistical analysis, we used the SPSS IBM vers.21 .


According to clinical guidelines, advice to stay active despite experiencing pain is recommended to patients with non-specific low back pain (LBP). However, not all patients receive guideline-concordant information and advice, and some patients still believe that activity avoidance will help them recover. The purpose was to study whether guideline-concordant beliefs among patients and other explanatory variables were associated with recovery. The main aim was to investigate whether believing staying active despite having pain is associated with a better functional outcome.This was a prospective cohort study involving adults with non-specific LBP referred from general practices to the Spine Centre at Silkeborg Regional Hospital, Denmark. Patients reported on their beliefs about the importance of finding the cause, the importance of diagnostic imaging, perceiving to have received advice to stay active, pain duration, pain intensity, and STarT Back Tool. Agreeing to: ‘An increase in pain is an indication that I should stop what I’m doing until the pain decreases’ adjusted for age, gender, and education level was the primary explanatory analysis. A 30% improvement in the Roland Morris Disability Questionnaire (RMDQ) score after 52 weeks was the outcome.P = 0.542 and unadjusted P = 0.629). However, STarT Back Tool high-risk patients had a less favourable functional outcome (adjusted P = 0.003 and unadjusted P = 0.002). Chronic pain was associated with less favourable functional outcome (adjusted P < 0.001 and unadjusted P < 0.001), whereas beliefs about finding the cause, diagnostic imaging, perceiving to have received advice to stay active, or pain intensity were not significantly associated with outcome.816 patients were included and 596 (73.0%) agreed that pain is a warning signal to stop being active. Among patients not considering pain as a warning signal, 80 (43.2%) had a favourable functional improvement of ≥30% on the RMDQ compared to 201 (41.2%) among patients considering pain a warning signal. No difference was found between the two groups  had a less favourable functional outcome.ClinicalTrials.gov (registration number: NCT03058315), 20 February 2017.Registered at  The one-month prevalence of low back pain (LBP) is estimated to be 23.2%, and many individuals with LBP consult their general practitioner for treatment , 2. In aperceive to have been recommended may differ from what they actually believe will help them recover [The information and recommendations healthcare professionals provide about LBP to their patients may differ from what their patients perceive they have been told . Moreove recover . Thus, c recover . Effecti recover , 14. Pat recover . More co recover . Further recover . The imp recover . ConsequThe main aim of this study was to investigate whether believing staying active despite having pain is associated with better functional outcomes among patients referred from general practice to an outpatient spine clinic in a secondary care setting in Denmark. Additional aims were to study the association between having received advice from a health professional to stay active, patients’ pain intensity, pain duration, and the STarT Back Tool and functional recovery. We hypothesised that patients who believe that staying active will help them recover would have higher odds of a 30%-improvement in the Roland Morris Disability Questionnaire (RMDQ) score after 52 weeks compared to patients who do not believe that staying active will help them recover.This is a prospective cohort study with a 52 weeks follow-up. Reporting follows the STROBE guidelines for observational studies in epidemiology . Data we1. ≥ 18 years of age at the time of completion of the baseline questionnaire.2. LBP is the primary cause of the referral to the Spine Centre.Known spinal fractures, infection, or inflammatory disease.The LBP is suspected to be caused by malignancy.Unwilling to participate.All patients referred to the Spine Centre are routinely provided with a standard electronic questionnaire one week prior to their appointment. Patients reporting LBP as their primary complaint were provided with further information about voluntary involvement in this study and were asked whether they wished to participate. All data were self-reported in questionnaires. Patients could, at any time and without any consequence for their treatment, discontinue their participation. Consenting patients were requested to reply to extra questions in addition to the standard questionnaire and to complete another questionnaire after 52 weeks. Patients not responding to the 52-week questionnaire were sent reminder emails after two and three weeks and delivered postal reminders after four weeks. Patients who still did not respond were contacted by telephone.The majority of questions included in the baseline questionnaire have been routinely administered since January 2016, with some adjustments following clinician-patient feedback to NR. The new questions included in the baseline questionnaire and the questions in the follow-up questionnaire were tested for face validity on 10 patients referred to the Spine Centre prior to this study. This testing process involved the patients completing the questionnaire with NR present and offering verbal feedback. This feedback led to minor question modifications. The RMDQ remained unchanged.‘An increase in pain is an indication that I should stop what I’m doing until the pain decreases.’ , a higher score indicating higher agreement).Patients were asked to rate their agreement with the following eight questions (explanatory variables). The primary explanatory was item 9 in the short form of the Örebro musculoskeletal pain screening questionnaire . The valThe scales were labelled 0 (do not agree) at the left side of the line and 10  at the right side. Scores of 0–5 were regarded as ‘disagreement’ and were coded 0; scores of 6–10 were regarded as ‘agreement’ and were coded 1.2)‘I think that finding the cause of pain is important for my recovery’ (0–10). Scores of 0–5 were regarded as ‘disagreement’, and scores of 6–10 were regarded as ‘agreement’.3)‘I think x-rays and MR scans are an important part of my recovery’ (0–10). Scores of 0–5 were regarded as ‘disagreement’, and scores of 6–10 were regarded as ‘agreement’.4)‘Have you been advised by your general practitioner to stay active despite your back pain?’ (y/n).5)Have you been advised by a physiotherapist or chiropractor to stay active despite your back pain?’ (y/n).6)Pain duration .7)Numerical pain rating (0–10) .8)The STarT Back Tool  . The STaOther included baseline variables: Health-related quality of life (EQ-5D-3 L) , age, geThe outcome was the proportion of patients indicating a clinically relevant improvement on the RMDQ score after 52 weeks, adjusted for age, gender, and educational level. A threshold of 30% improvement between baseline and 52 weeks was considered a clinically relevant improvement . This waP < 0.01. Analyses were performed in Stata (IC version 15.1) . This study is registered at ClinicalTrials.gov (registration number: NCT03058315).Reporting of baseline characteristics includes numbers (%) for categorical variables and means (SD) or medians (IQRs) for continuous variables depending on the distribution of the data. Responses 0–5 or 6–10) to the question ‘An increase in pain is an indication that I should stop what I’m doing until the pain decreases’ was considered the primary explanatory variable. Responses to ‘I think that finding the cause of pain is important for my recovery’, ‘I think x-rays and MR scans are an important part of my recovery’, ‘Have you been advised by your general practitioner to stay active despite your back pain?’, Have you been advised by a physiotherapist or chiropractor to stay active despite your back pain?’, pain duration (≥ 12 weeks), numerical pain rating (0–10), and the STarT Back Tool (high-risk group) were all considered secondary explanatory variables. The outcome (RMDQ) was adjusted for possible confounders  in a logistic regression analysis and analysed unadjusted in logistic regression models estimating the odds of clinically relevant improvement (30%) in the RMDQ score  was blinded to the RMDQ score after 52 weeks while cleaning the dataset (baseline data). A new dataset with only baseline RMDQ and RMDQ after 52 weeks was delivered by (NR) to (AR) after follow-up was completed. This was done to ensure blinding during cleaning and coding.Between 1 April 2017 and 22 December 2017, 1789 patients with LBP were invited to participate in this study, and 828 agreed. Of these, 816 fulfilled the inclusion criteria and were included , and 454 (55.6%) were women. Of the participants, 739 (90.6%) had chronic LBP; the mean NPR was 5.2 (SD 2.4), and the mean RMDQ score was 14.0 (SD 4.9). Of these, 596 (73.0%) agreed that pain is a warning signal to stop being active, 717 (88.0%) considered MR scans and x-rays to be important for their recovery, and 301 (37.0%) were ‘high-risk’ patients according to the STarT Back Tool . Without confounder adjustment, the p-value was 0.629.Follow-up data were available for 673 82.5%) of the patients Fig. . The ave.5% of thP = 0.836).Among patients not considering x-rays and scans important for their recovery, 36 (42.9%) had a favourable functional improvement of ≥30% on the RMDQ compared to 245 (41.7%) among patients considering x-rays and scans important for their recovery. Adjusted for age, gender, and educational level, no significant difference was found between the two groups (P = 0.003).Among patients in the STarT Back Tool medium or low-risk group, 201 (46.2%) had a favourable functional improvement compared to 80 (33.8%) among patients in the STarT Back Tool high-risk group. Adjusted for age, gender, and educational level, the difference was statistically significant (P < 0.001). Numerical pain rating (P = 0.069) and advice to stay active from a GP (P = 0.218) or a physiotherapist or chiropractor (P = 0.933) were not found to be associated with an improvement in RMDQ.Pain duration was statistically significantly associated with a clinically relevant improvement in the RMDQ  question to measure the patients’ views on the importance of staying active (part of the Örebro questionnaire ). This D0 questioIn this prospective study, we found that 73% of patients considered pain a warning signal to stop being active, which was much more than the expected 33% . FurtherIn the STarT Back Tool questions, 5–9 comprise the psychosocial score that determines the high-risk classification . Only 37A high percentage of these patients referred to secondary care for LBP held erroneous beliefs that may hinder their recovery. According to clinical guidelines for the management of LBP –6, primaShifting patients’ pain beliefs from the traditional biomedical perspective that pain is an indicator of tissue damage and towards a perspective (based on a contemporary understanding of pain) that supports staying active despite pain has previously been found to be difficult  and is lPatients with LBP frequently hold erroneous beliefs that may be detrimental for their recovery. However, considering pain a warning signal was not associated with a favourable functional improvement. In addition, guideline-concordant beliefs about scans and x-rays, having been advised to stay active by a healthcare professional, and patients’ levels of pain were not associated with a favourable functional improvement. However, having chronic pain and belonging to the high-risk group, according to the STarT Back Tool, were associated with worse functional outcomes.


Eutectic mixture of local anesthetics (EMLA) cream is often used for local anesthesia during spinal injections. However, this agent has delayed onset of action while vapocoolant spray serves more advantages. The vapocoolant spray containing ethyl chloride has fast onset and is safe, low cost, and widely available. This study aimed at comparing the effectiveness of vapocoolant spray and EMLA cream in reducing pain for spinal injections.  This was an experimental study on 94 subjects with 47 subjects treated with EMLA cream and 47 subjects treated with vapocoolant spray. The effectiveness of anesthesia was assessed by using Numeric Pain Rating Scale (NPRS) and patient movement during the surgery. U test. For patient movement, the movement was reported only in one (2.1%) patient in the EMLA group and one (2.1%) patient in the vapocoolant spray group. Based on Fisher's test, there was no significant difference between the two groups for patient movement.  This study found that the pain scale was NPRS 0 (0–3) for the EMLA group and NPRS 0 (0–4) for the vapocoolant spray group. There was no significant difference between two groups for pain scale according to the Mann–Whitney  Both EMLA cream and vapocoolant spray were equally effective in reducing pain during spinal injection. There was no difference in degree of pain reduction and patient movement between the EMLA cream group and the vapocoolant spray group during spinal injection. Pain during any medical procedures, including spinal anesthesia, should be managed carefully as this would affect the perception and comfort of the patients , 2. Kim Local anesthetic agents may be administered to relieve the pain during any injections. Anesthetic agents often used are eutectic mixture of local anesthetics (EMLA) cream, ethyl chloride, nonsteroidal anti-inflammatory drugs (NSAIDs), lidocaine, and opioid –6. EMLA The vapocoolant spray contains ethyl chloride which serves as topical anesthetic agents. The vapocoolant spray generates cooling effect on the skin surface. There are many advantages of this agent, including fast onset of action, its safety profile, and low cost, and it is widely available . The mecPast studies have mentioned the wide indications of vapocoolant spray for many medical procedures. Celik et al. have compared the administration of vapocoolant spray, EMLA cream, and placebo cream during venous cannulation among patients undergoing hemodialysis. The result showed that both vapocoolant spray and EMLA cream significantly decreased the pain intensity during injections .Based on the preliminary study conducted during February 2016 in Cipto Mangunkusumo Hospital, there were 94.3% of respondents who had movements during spinal injections by using 27 G needle. Additionally, there were 5.7% respondents with pain score of 5, 25.7% respondents with pain scale of 3, 51.4% respondents with pain scale of 2, and 17.1% respondents with pain score of 1. The mean pain score for all respondents undergoing spinal injections was 2.3.In Indonesia, currently there is no study regarding the use of vapocoolant spray as local anesthetic agent during spinal injections. However, this agent is cheaper and widely available in the daily practice in comparison with EMLA cream. This study aimed to compare the effectiveness between vapocoolant spray and EMLA cream as the local anesthetic agent during spinal injections.This was an experimental study conducted in a stereotactic operating room of Cipto Mangunkusumo Hospital from October 2016 to January 2017. Research subjects were divided into two groups with administration of vapocoolant spray containing ethyl chloride for the treatment group and EMLA cream for the control group.Inclusion criteria were adult subjects over the age of 18 undergoing first brachytherapy procedure and planned for spinal anesthesia and having physical status of the American Society of Anesthesiologist (ASA) I–III. Exclusion criteria were subjects with allergy to anesthetic drugs, hemodynamically unstable, contraindications to spinal injection, unwilling to sign informed consent, and current consumption of psychiatric drug. Drop-out criteria were subjects with allergic reaction during injection, refractory hypotension (decreased blood pressure >20%) despite of administration of ephedrine, and refractory desaturation  despite of positive ventilation pressure.clinicaltrials.gov (NCT 03134391), research subjects were randomized by using block randomization into control and experimental group. All subjects had 22 G intravenous cannula with ringer acetate fluid administration. Mean arterial pressure (MAP), pulse rate, respiratory rate, and peripheral capillary oxygen saturation (SpO2) were recorded. Patients were positioned in sitting position with the head flexed and back arched posteriorly. Spinal injection site was identified in the L4-5 intervertebral space.There were 94 subjects with 47 subjects for each group consecutively. Following the ethical clearance, and registered in In the EMLA group, research subjects received 2 ml of EMLA cream containing a mixture of 2.5% lidocaine and 2.5% prilocaine in oil/water emulsion and further covered by clear dressing for 45–60 minutes. In the vapocoolant spray group, the patient received a spray from a vapocoolant pressure pack with a distance of about 10 cm from the surface for two seconds and at least 10 seconds for the vapocoolant spray to vaporize.Spinal injection was conducted by using 27 G spinal needle with pointed tip with the bevel parallel to the durafiber. Spinal injection was conducted by a final year anesthesiologist resident. Pain intensity was measured by using NPRS, and patient movement was recorded to measure the success of anesthesia. Vital signs were observed every three minutes for the first 15 minutes and every five minutes until completion of the procedure.T-test and chi-squared test if data had normal distribution and Mann–Whitney U test and Fisher's exact test if data had nonnormal distribution.Data analysis was performed by using the Statistical Package for the Social Sciences (SPSS) for Windows version 20.0. NPRS score and patient movement was analyzed by using the independent There were no subjects that dropped out during the study . BaselinData on pain intensity using NPRS and patient movement in both groups are shown in Tables 2) according to time is shown in T-test results, there were no significant differences for hemodynamic profile in the form of MAP, pulse rate, respiratory rate, and SpO2.There were no allergic reactions occurred during the study. There was no occurrence of desaturation/apnea events, bradycardia, nausea, vomiting, respiratory depression, hypotension, and agitation in both groups. Analysis of hemodynamic profile (MAP, pulse rate, respiratory rate, and SpOThis study aimed to compare the effectiveness of vapocoolant spray and EMLA cream in reducing pain for spinal injections. Based on pain assessment in this study generated, there was no statistically significant pain scale difference between these two. This was similar with previous study by Cohen et al., in which found there were no significant differences in the duration of crying, pain-related behavior, and pain based on child-scored faces scale and parent-scored faces scale . ConversThe ability to reduce pain following spinal injections between EMLA cream and vapocoolant spray was comparable. Both anesthetic agents might be utilized to reduce pain during regional anesthesia, including spinal injections. However, this study could not generate the similar finding for other medical procedures that required larger diameter of cannula. Further study should be conducted with different medical procedures.Allergic reaction and other adverse event related with the procedure, such as desaturation/apnea events, bradycardia, nausea, vomiting, respiratory depression, hypotension, and agitation, were recorded in this study. However, there was no such finding in this study. The literature showed that the side effects associated with vapocoolant spray and EMLA cream anesthetic were quite rare. Çelik et al. mentioned only one subject suffered from allergic reaction following the administration of EMLA cream . Any topThis study found that in both groups, majority of patients moved during spinal injection similar to the preliminary study in which more than 90% of patients moved during the spinal injection. Therefore, the presence of local anesthetic during spinal injection did not affect any movement during spinal injection . MovemenBoth anesthetic agents were widely available in the daily practice with excellent safety profile. EMLA cream is commonly used for local anesthesia in spinal injection. This study has shown that with regard to the ability to reduce pain during spinal injection, there was no significant difference between these two agents. However, one of the disadvantages of EMLA cream is its delayed onset of action; the patients should wait up to 60 minutes before injection after the administration of the EMLA cream. On the contrary, the vapocoolant spray showed that it has a rapid onset of action in which the patient only needed to wait for ten seconds before injection. This difference was clinically significant so that the vapocoolant spray was more suitable for any procedure that required shorter preparation time, such as emergency procedure. Additionally, both surgeons and patients did not have to wait an hour before starting the anesthesia procedure. Therefore, this was the main advantage of the vapocoolant spray.There was some limitation in this study. Due to the preparation of both agents, it was difficult to do blinding for both researcher and subjects. Additionally, pain scale by using NPRS was a subjective assessment even though pain perception is subjective for each patient. However, this could create bias in this study. This study did not measure the difference in duration of the spinal anesthesia procedure. Reduced pain might affect the duration as well as the success rate of the spinal injection.Administration of EMLA cream and vapocoolant spray was equally effective in reducing pain during spinal injection. There was no difference in terms of pain reduction between the EMLA cream group and the vapocoolant spray group during spinal injection.