Epidemiology of Upper Limb Complex Regional Pain Syndrome in a Retrospective Cohort of Persons Aged 9-30 Years, 2002-2017.

Introduction This paper describes the epidemiology and clinical presentation of complex regional pain syndrome (CRPS) in a large, integrated health care delivery system; and CRPS incidence rates (IRs) over a time period spanning human papillomavirus (HPV) vaccine licensure and published case reports of CRPS following HPV vaccination. Methods The authors examined CRPS diagnoses in patients aged 9-30 years between January 2002 and December 2017 using electronic medical records, excluding patients with lower limb diagnoses only. Medical record abstraction and adjudication were conducted to verify diagnoses and describe clinical characteristics. CRPS IRs were calculated for 3 periods: Period 1 (2002-2006: before HPV vaccine licensure), Period 2 (2007-2012: after licensure but before published case reports), and Period 3 (2013-2017: after published case reports). Results A total of 231 individuals received an upper limb or unspecified CRPS diagnosis code during the study period; 113 cases were verified through abstraction and adjudication. Most verified cases (73%) were associated with a clear precipitating event (eg, non-vaccine-related injury, surgical procedure). The authors identified only 1 case in which a practitioner attributed CRPS onset to HPV vaccination. Twenty-five incident cases occurred in Period 1 (IR = 4.35/100,000 person-years (PY), 95% confidence interval (CI) = 2.94-6.44), 42 in Period 2 (IR = 5.94/100,000 PY, 95% CI = 4.39-8.04), and 29 in Period 3 (IR = 4.53/100,000 PY, 95% CI = 3.15-6.52); differences between periods were not statistically significant. Conclusion These data provide a comprehensive assessment of the epidemiology and characteristics of CRPS in children and young adults and provide further reassurance about the safety of HPV vaccination.

Comparison of Epidemiological Data of Complex Regional Pain Syndrome (CRPS) Patients in Relation to Disease Severity-A Retrospective Single-Center Study.

A retrospective data analysis of 159 complex regional pain syndrome (CRPS) patients (n = 116 women, 73.0%, mean age 60.9 ± 14.4 years; n = 43 men, 27.0%, mean age 52.3 ± 16.7 years) was performed from 2009 to 2020. The right side was affected in 74 patients (46.5%), the left in 84 patients (52.8%), and 1 patient (0.7%) developed a bilateral CRPS. Data were analyzed for the frequency and distribution of symptoms. The number of reduction maneuvers and the number of Budapest criteria were compared in relation to the severity of CRPS. Hand and wrist (n = 107, 67.3%), followed by foot and ankle (n = 36, 22.6%) and other locations (n = 16, 10.1%) were mainly affected by CRPS. The main causes included direct trauma (n = 120, 75.5%), surgery without previous trauma (n = 25, 15.7%), other causes (n = 9, 5.7%), and spontaneous development (n = 3, 1.9%); there was also missing documentation (n = 2, 1.3%). The most common symptoms were difference in temperature (n = 156, 98.1%), limitation of movement (n = 149, 93.7%), and swelling (n = 146, 91.8%). There was no correlation between the number of reduction maneuvers and the number of Budapest criteria. In summary, patients with the following constellation are at increased risk of CRPS: a female, over 60 years old, who has fallen and has sustained a fracture in the hand or wrist with persistent pain and has been immobilized with a cast for approx. 4 weeks.

Relative Prevalence and Associated Factors of Complex Regional Pain Syndrome Type I in Patients with Radial Head Fractures Treated with Open Reduction and Internal Fixation: A Cross-Sectional Study.

Objective: This cross-sectional study aimed to examine the incidence and associated factors of complex regional pain syndrome type I (CRPS I) in patients who underwent open reduction and internal fixation (ORIF) for radial head fractures. Methods: The study enrolled 601 radial head fracture patients treated with ORIF, 523 of which completed the 1-year follow-up. The incidence of CRPS I in those patients was assessed using the Budapest criteria. Patients were then divided into 2 groups: patients with CRPS I (n = 28) and patients without CRPS I (n = 495). The patients' demographic and clinical data before the operation were prospectively collected by our team. Independent t-tests and χ 2 tests were used as univariate analyses to compare the demographic and clinical data between the two groups. Meanwhile, multivariate regression analysis was conducted to identify the associated risk factors for CRPS I. Results: The incidence of CRPS I in patients with radial head fractures treated with ORIF was 5.5% during the first year following surgery. Significant differences were observed in age, gender, type of trauma, modified Mason Classification, and depressive personality disorders. The logistic regression analysis revealed that the female gender, modified Mason type III fractures, and depressive patients were significantly more likely to develop CRPS I (p=0.021, 0.023, and 0.025, respectively). Conclusions: The incidence of CRPS I among radial head fracture patients undergoing ORIF was 5.5%. In addition, early detection of CRPS I and providing adequate intervention will likely result in greater benefits for those patients.

Determinants of Complex Regional Pain Syndrome Type I among Radial Head Fracture Patients with Unilateral Arthroplasty.

OBJECTIVE: This study aims to assess the proportions of complex regional pain syndrome type I (CRPS I) in radial head fracture patients undergoing unilateral arthroplasty and to explore associated factors. METHODS: This is a prospective observational study. From March 2016 to May 2019, a total of 221 adult patients with radial head fracture patients were included in consecutive studies and completed the 1-year follow-up. All patients were treated by unilateral arthroplasty. At each follow-up visit, the visual analogue scale was used to measure patients' pain level. Occurrence of CRPS I, which was diagnosed by Budapest criteria, was the main outcome collected at baseline and the 1-, 3-, 6-, and 9-month follow-ups. The baseline data were collected before surgery and included demographic and clinical data. Independent t-tests and χ2 tests were used as univariate analyses to compare the baseline data of patients with and without CRPS I. Multivariate analysis (Backword-Wald) was used to identify factors independently associated with CRPS I. RESULTS: The proportion of CRPS I cases among radial head fracture patients undergoing unilateral arthroplasty was 11% (n = 24). A total of 19 (79%) patients were diagnosed with CRPS I within 1 month after surgery. Multivariable logistic regression analysis revealed that female gender (odds ratios [OR]: 1.537; 95% confidence interval [CI]: 1.138-2.072), age younger than 60 years (OR: 1.682; 95% CI: 1.246-2.267), moderate and severe Mayo Elbow Performance Score (MEPS) pain (OR: 3.229; 95% CI: 2.392-4.351) and anxiety (OR: 83.346; 95% CI: 61.752-112.320) were independently associated with CRPS I. CONCLUSIONS: This exploratory study reported that the incidence of CRPS I developing after radial head arthroplasty was 11%. Female sex, younger age, moderate and severe MEPS pain and anxiety patients seems more likely to develop CRPS I.

Preoperative Predictors of Complex Regional Pain Syndrome Outcomes in the 6 Months Following Total Knee Arthroplasty.

This prospective observational study evaluated preoperative predictors of complex regional pain syndrome (CRPS) outcomes in the 6 months following total knee arthroplasty (TKA). Participants were n = 110 osteoarthritis patients (64.5% female) undergoing unilateral TKA with no prior CRPS history. Domains of negative affect (depression, anxiety, catastrophizing), pain (intensity, widespread pain, temporal summation of pain [TSP]), pain interference, sleep disturbance, and pro-inflammatory status (tumor necrosis factor-alpha [TNF-a]) were assessed preoperatively. CRPS outcomes at 6-week and 6-month follow-up included the continuous CRPS Severity Score (CSS) and dichotomous CRPS diagnoses (2012 IASP criteria). At 6 months, 12.7% of participants met CRPS criteria, exhibiting a "warm CRPS" phenotype. Six-week CSS scores were predicted by greater preoperative depression, anxiety, catastrophizing, TSP, pain intensity, sleep disturbance, and TNF-a (P's < .05). Provisional CRPS diagnosis at 6 weeks was predicted by higher preoperative TSP, sleep disturbance, and TNF-a (P's < .05). CSS scores at 6 months were predicted by more widespread and intense preoperative pain, and higher preoperative TSP, pain interference, and TNF-a (P's < .01). CRPS diagnosis at 6 months was predicted only by more widespread and intense pain preoperatively (P's < .05). Risk for CRPS following TKA appears to involve preoperative central sensitization and inflammatory mechanisms. Preoperative negative affect is unlikely to directly influence long-term CRPS risk. PERSPECTIVE: This article identifies preoperative predictors of CRPS features at 6 months following total knee arthroplasty, including more widespread pain and higher pain intensity, temporal summation of pain, pain interference, and tumor necrosis factor-alpha levels. Findings suggest the importance of central sensitization and inflammatory mechanisms in CRPS risk following tissue trauma.

Separating Fact From Fiction: A Nationwide Longitudinal Examination of Complex Regional Pain Syndrome Following Treatment of Dupuytren Contracture.

BACKGROUND: One of the most feared complications following treatment of Dupuytren contracture is complex regional pain syndrome (CRPS). This study aims to provide a national perspective on the incidence of CRPS following treatment of Dupuytren contracture and identify patient factors to target for risk reduction. METHODS: Using the Truven MarketScan databases from 2007 to 2016, individuals aged ≥18 years who developed CRPS within 1 year of treatment of Dupuytren contracture were identified using the International Classification of Disease diagnosis code for CRPS. Predictor variables included: age, sex, employment status, region, type of procedure, and concurrent carpal tunnel surgery. Multivariable logistic regression was used to analyze outcomes. RESULTS: In all, 48 327 patients received treatment for Dupuytren contracture, including collagenase injection (13.6%); percutaneous palmar fasciotomy (10.3%); open palmar fasciotomy (3.9%); palmar fasciectomy with 0 (10.8%), 1 (29.2%), or multiple (19.6%) digit releases; or a combination of these procedures (12.8%). One hundred forty-five patients (0.31%) were diagnosed with CRPS at a mean of 3.4 months (standard deviation, 2.3) following treatment. Significant predictors of CRPS included female sex (odds ratio [OR], 2.02; P < .001), Southern region (OR, 1.80; P = .022), long-term disability status (OR, 4.73; P = .035), palmar fasciectomy with release of 1 (OR, 5.91; P = .003) or >1 digit (OR, 13.32; P < .001), or multiple concurrent procedures for Dupuytren contracture (OR, 8.23; P = .001). CONCLUSIONS: Based on national commercial claims data, there is a lower incidence of CRPS following treatment of Dupuytren contracture than previously reported. Risk factors identified should help with preoperative counseling and assist clinicians in targeting risk reduction measures.

Effect of Perioperative Vitamin C on the Incidence of Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis.

Complex regional pain syndrome type 1 (CRPS-I) is a complex complication that occurs after limb extremity surgeries. Controversy exists regarding the effectiveness of vitamin C in reducing that condition. Therefore, we conducted this systematic review and meta-analysis to assess the role of vitamin C on CRPS-I and functional outcomes after distal radius, wrist, foot, and ankle surgeries. We searched Medline (via PubMed), Embase, the Cochrane Library, Clinicaltrial.gov, and Google Scholar for relevant studies comparing perioperative vitamin C versus placebo after distal radius, wrist, foot, and ankle surgeries from infinity to May 2021. Continuous data such as functional outcomes and pain scores were pooled as mean differences, while dichotomous variables such as the incidence of complex regional pain syndrome and complications were pooled as odds ratios, with 95% confidence interval, using R software (meta package, version 4.9-0) for Windows. Eight studies were included. The timeframe for vitamin C administration in each study ranged from 42 to 50 days postinjury and/or surgical fixation. The effect size showed that vitamin C was associated with a decreased rate of CRPS-1 than placebo (odds ratio 0.33, 95% confidence interval [0.17, 0.63]). No significant difference was found between vitamin C and placebo in terms of complications (odds ratio 1.90, 95% confidence interval [0.99, 3.65]), functional outcomes (mean difference 6.37, 95% confidence interval [-1.40, 14.15]), and pain scores (mean difference -0.14, 95% confidence interval [-1.07, 0.79]). Overall, vitamin C was associated with a decreased rate of CRPS-I than placebo, while no significant difference was found regarding complications, functional outcomes, and pain scores. These results hold true when stratifying fracture type (distal radius, ankle, and foot surgeries) and vitamin C dose (500 mg or 1 g).

Complex Regional Pain Syndrome in Athletes: Scoping Review.

Background and Objectives: Complex regional pain syndrome (CRPS) is a chronic condition characterized by disproportionate regional pain, usually affecting distal limbs, that follows trauma or surgery. Athletes may develop CRPS because of exposure to traumatic or overuse injuries. The aim of the present study is to review the available literature about CRPS type 1 in athletes. Materials and Methods: We searched two online databases (PubMed and Web of Science), selecting papers aiming at investigating CRPS type 1 (algodystrophy) in athletes. The analysis of databases was made considering original articles published until 30 June 2021, written in English. Results: Fifteen papers (12 case reports, 3 case series) were selected for a total of 20 clinical cases (15 females, 5 males), aged between 10 and 46 years (mean age 18.4 ± 9.8 standard deviation years). Patients included practiced different types of sport (soccer, athletics, gymnastics, basketball). The most involved anatomical sites were lower limbs, and time to diagnosis ranged from 2 days to 4 years. The most used treatments were pharmacological and physical therapies, but sometimes invasive approaches, as regional nerve, or lumbar sympathetic blocks, were provided. The main assessed outcomes were return to activity and pain. Conclusions: Our review suggests a higher prevalence of CRPS type 1 in younger people and in lower limbs than in general population but confirms the higher prevalence in females. However, the number of studies addressing CRPS in athletes is limited, as well as the number of involved patients, considering that only few and heterogeneous case reports were published about this topic. Moreover, the high prevalence of old studies (only 5 available studies in the last 10 years) might have influenced the choice of both assessment tools and management strategies. Despite these limitations, athletes showing disproportionate pain after sport-related injury should be promptly evaluated and treated through a multidimensional approach to avoid long-term consequences of algodystrophy.

Vitamin C prevention of complex regional pain syndrome after foot and ankle surgery: a prospective randomized study of three hundred and twenty nine patients.

PURPOSE: Complex regional pain syndrome (CRPS) after foot and ankle surgery has a significant impact on the ability to walk. As the symptomatic treatment of this disaster complication is poor and has low efficacy, a preventive treatment would be beneficial. Vitamin C has been reported to be efficient in preventing CRPS in elective scheduled surgery. Few authors explored this efficiency in foot and ankle surgery. We, therefore, evaluated the efficacy of vitamin C in preventing this complication after foot and ankle surgeries for both trauma and elective surgery. MATERIAL AND METHODS: Between January 2018 and December 2019, 329 patients were included in the study. We conducted a prospective randomized study on the efficiency of vitamin C (one group with and one without vitamin C) to prevent CRPS risk in patients operated in our institution on foot or ankle surgery. The incidence of CRPS after foot and ankle surgery was evaluated in both groups; the diagnostic of CRPS was made using the Budapest criteria associated with three-phase bone scintigraphy. RESULTS: Among the 329 patients included in the study (232 women and 97 men), 121 patients were included in the vitamin C group and 208 in the control group (without vitamin C). Vitamin C was statistically linked with a decreased risk of CRPS (OR 0.19; CI 95% from 0.05 to 0.8; p = 0.021). Alcoholism and cast immobilization were increased risks factors of CRPS (respectively p = 0.001 and p = 0.034). CONCLUSION: Taking 1 g per day of vitamin C during 40 days after a foot or ankle surgery reduces the risk of CRPS.

Prospective randomized study of the vitamin C effect on pain and complex pain regional syndrome after total knee arthroplasty.

PURPOSE: Complex regional pain syndrome (CRPS) type I, formerly known as reflex sympathetic dystrophy (RSD) or algodystrophy, is a condition with chronic pain condition following a trauma or surgery. The physiopathology of this syndrome remained incompletely known. Due to the lack of effective curative treatment, prevention of this complication is important. Therefore, we evaluated the efficacy of vitamin C in preventing this complication. MATERIAL AND METHODS: Between January 2018 and July 2019, we conducted a prospective randomized study on the efficiency of vitamin C (one group with and one without vitamin C) on prevention of CRPS risk in patients operated in our institution with TKA. Patients with a VAS pain score > 4 performed a three-phase bone scintigraphy. The diagnostic of CRPS was made by using the Budapest criteria associated to a bone scintigraphy. Statistical significance was set at p < 0.05 RESULTS: One hundred fifty-three patients were included in the vitamin C group, 139 in the control group without vitamin C. For the entire cohort, the prevalence of complex regional pain syndrome was 7.9% (23 of 292). The prevalence of complex regional pain syndrome was 3.9% (six of 153) in the vitamin C group and 12.2% (seventeen of 139) in the control group (p = 0.008). After multivariate regression, vitamin C was found to be an independent preventive factor of CRPS and there was a significant difference between the vitamin C group and the control group (relative risk, 0.27; 95% confidence interval, 0.1-0.8; p = 0.015). CONCLUSION: Taking 1 g per day of vitamin C during 40 days after a TKA reduces the risk of CRPS.

Regional vitamin C in Bier block reduces the incidence of CRPS-1 following distal radius fracture surgery.

BACKGROUND: Systemic vitamin C supplementation after wrist fracture has been suggested to reduce the incidence of complex regional pain syndrome (CRPS). This study aimed to evaluate the effect of regional vitamin C in Bier block in the early phase of fracture on CRPS occurrence following surgery for distal radius fractures. METHODS: Seventy-four patients with isolated extra-articular distal radius fracture with the plan of fixation under Bier block were enrolled. Patients were assigned randomly into two groups: receiving either 500 mg vitamin C or sterile water as a Bier block adjuvant. Both groups received 500 mg of oral vitamin C for six weeks. The patients were evaluated for CRPS signs and symptoms at 2, 4, 6, and 12 weeks post-surgery. RESULTS: The overall incidence of CRPS 12 weeks after surgery in the vitamin C group was significantly less than the controls (22.9% vs 45.5%, p = 0.04). Logistic regression analysis showed that the only significant contribution in predicting the incidence of CRPS came from the intervention variable (OR 0.26, CI95% 0.08-0.85; P = 0.027). CONCLUSIONS: The findings suggest that adding vitamin C 500 mg to the local anesthetic in Bier block significantly reduces the incidence of CRPS following distal radius fractures.

The spectrum of pediatric amplified musculoskeletal pain syndrome.

BACKGROUND: Children presenting with musculoskeletal pain to pediatric rheumatology clinics are very heterogeneous and on a continuum from those with localized pain to total body pain. Many report intermittent, rather than constant, pain. We examined clinical and psychological characteristics of these children at presentation and specifically those who fulfilled the criteria for fibromyalgia. METHODS: We performed a retrospective, cross-sectional cohort study of children under ≤18 years old presenting to the pediatric rheumatology pain clinic between January 2015 and July 2019 and enrolled in a patient registry. We included children diagnosed with amplified pain, excluding those fulfilling criteria for complex regional pain syndrome. Abstracted data included clinical characteristics, pain symptoms, functional disability inventory (FDI), widespread pain index, and symptom severity scale. RESULTS: We analyzed 636 subjects, predominantly non-Hispanic Caucasian females. Using median split method, 54% had diffuse pain (≥ 5 body regions involved), but, of these, only 58% met criteria for fibromyalgia. Subjects with diffuse pain, compared to those with localized pain had a longer duration of pain (24 vs 12 months, p < 0.01), reported greater pain intensity (6/10 vs 5/10, p < 0.001), greater mental health burden, and poorer function (FDI 25 vs 19, p < 0.0001). Subjects with limited pain more often reported a history of trigger event (34% vs 24%, p < 0.01) but not autonomic changes (14% vs 14%, p = 0.94). The presence of adverse childhood experiences did not differ among those with limited versus diffuse pain except for parental divorce (16% vs 23%, p = 0.03). Intermittent pain was reported in 117 children (18%) and, compared to subjects with constant pain, they reported less pain (0/10 vs 6/10) and were more functional (FDI 13 vs 25) (both p < 0.0001). CONCLUSIONS: There exists a wide spectrum of pain manifestations among children with amplified pain including limited or diffuse and constant or intermittent pain. Most children who presented to our clinic did not fulfill criteria for fibromyalgia but nonetheless had significant symptoms and disability. Studies focusing on fibromyalgia may miss the full extent of childhood amplified pain. Additionally, research limited to those meeting the fibromyalgia criteria likely underestimate the significant impact of amplified pain among the pediatric population.

Association between quadrivalent human papillomavirus vaccination and selected syndromes with autonomic dysfunction in Danish females: population based, self-controlled, case series analysis.

OBJECTIVE: To evaluate the association between quadrivalent human papillomavirus vaccination and syndromes with autonomic dysfunction, such as chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome. DESIGN: Population-based self-controlled case series. SETTING: Information on human papillomavirus vaccinations and selected syndromes with autonomic dysfunction (chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome) identified using ICD-10 (international classification of diseases, revision 10) diagnostic codes from Danish nationwide registers. PARTICIPANTS: 869 patients with autonomic dysfunction syndromes from a cohort of 1 375 737 Danish born female participants aged 10 to 44 years during 2007-16. MAIN OUTCOME MEASURES: Self-controlled case series rate ratios (95% confidence intervals) of the composite outcome of chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome, adjusted for age and season, comparing female participants vaccinated and unvaccinated with the quadrivalent human papillomavirus vaccine. Chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome were also considered separately in secondary analyses. RESULTS: During 10 581 902 person years of follow-up, 869 female participants with syndromes of autonomic dysfunction (136 with chronic fatigue syndrome, 535 with complex regional pain syndrome, and 198 with postural orthostatic tachycardia syndrome) were identified. Quadrivalent human papillomavirus vaccination did not statistically significantly increase the rate of a composite outcome of all syndromes with autonomic dysfunction in a 365 day risk period following vaccination (rate ratio 0.99, 95% confidence interval 0.74 to 1.32) or the rate of any individual syndrome in the risk period (chronic fatigue syndrome (0.38, 0.13 to 1.09), complex regional pain syndrome (1.31, 0.91 to 1.90), or postural orthostatic tachycardia syndrome (0.86, 0.48 to 1.54)). CONCLUSIONS: When vaccination is introduced, adverse events could occur in close temporal relation to the vaccine purely by chance. These results do not support a causal association between quadrivalent human papillomavirus vaccination and chronic fatigue syndrome, complex regional pain syndrome, or postural orthostatic tachycardia syndrome, either individually or as a composite outcome. An increased risk of up to 32% cannot be formally excluded, but the statistical power of the study suggests that a larger increase in the rate of any syndrome associated with vaccination is unlikely.

Bodily changes and sensory sensitivity in complex regional pain syndrome and fibromyalgia.

Complex regional pain syndrome (CRPS) and fibromyalgia are chronic pain conditions of unexplained origins. In addition to symptoms in the diagnostic criteria, patients can report changes to vision and other sensations or bodily functions. It is unclear whether these are greater than would be expected due to normal ageing, living with chronic pain generally, or common comorbidities of chronic pain such as depression or anxiety. We administered an on-line survey evaluating the frequencies and types of self-reported somatic symptoms, bodily changes, and sensory sensitivity in respondents with CRPS (n = 390), fibromyalgia (n = 425), and both CRPS and fibromyalgia ("CRPS+fibromyalgia"; n = 88) compared to respondents with other chronic pain conditions (n = 331) and pain-free controls (n = 441). The survey assessed somatic symptoms (Patient Health Questionnaire-15), bodily changes, pain/discomfort/distress triggers, and pain intensifiers. We conducted analysis of covariance's with age, sex, Patient Health Questionnaire-9 (measuring depression), Generalized Anxiety Disorder-7, pain duration in years, hours of pain per day, and number of pain-related medical diagnoses as covariates. After controlling for covariates, respondents with CRPS and/or fibromyalgia reported more somatic symptoms, changes in movement and biological responses, pain/discomfort/distress triggers, and pain intensifiers than pain(-free) control groups. Fibromyalgia specifically related to changes in vision and hearing, urinary/intestinal function, and drinking and eating. Complex regional pain syndrome related to changes in hair, skin, and nails; and infection and healing. The CRPS+fibromyalgia group presented with features of both disorders with minimal additional stressors or symptoms over and above these. Our findings suggest that CRPS and fibromyalgia share underlying pathophysiologies, although specific mechanisms might be different.

Hazard of complex regional pain syndrome following human papillomavirus vaccination among adolescent girls in the United States: a case-cohort analysis of insurance claims data.

Objectives: Complex regional pain syndrome (CRPS) cases have followed human papillomavirus (HPV) vaccination, but no causal link has been established.Methods: Using insurance claims, the authors observed unvaccinated 11-year-old girls for CRPS diagnoses. The authors used time-dependent Cox regression to identify health-related CRPS predictors using diagnosis codes. Next, the authors identified HPV vaccinations using procedural codes. HPV vaccination and CRPS predictors were considered time-dependent covariates to estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) for CRPS, 30, 90, and 180-days post-vaccination.Results: 1,232,572 girls received 563 unique CRPS diagnoses. In a 10% sub-cohort of 123,981 girls accounting for potential confounders and predisposing risk factors (i.e. injury, infection, mental illness, primary care use), CRPS hazard was not significantly elevated 30 days (HR: 0.90, 95% CI: 0.46, 1.73), 90 days (HR: 1.17, 95% CI: 0.83, 1.65), or 180-days post-vaccination (HR: 1.11, 95% CI: 0.83, 1.47).Conclusion: The results support the safety and continued administration of HPV vaccines to adolescents.

The Impact of Tobacco Smoking on Spinal Cord Stimulation Effectiveness in Complex Regional Pain Syndrome Patients.

OBJECTIVES: We aim to investigate the correlation of smoking and spinal cord stimulation (SCS) effectiveness for pain relief in complex regional pain syndrome (CRPS) patients while controlling for possible confounding factors including opioid intake. MATERIALS AND METHODS: Following Institutional Review Board approval, a retrospective cohort study was performed by collecting data for all CRPS patients treated with SCS at Cleveland Clinic between 1998 and 2013. We divided patients into three groups based on their smoking status at the time of SCS device implant: Current smokers, former smokers, or nonsmokers. We used a linear mixed modeling to assess the association between smoking status and pain score at baseline and at 3, 6, and 12 months. We then used pairwise t-tests for post hoc comparisons of pain scores. RESULTS: Of the 420 CRPS patients treated with SCS implants, the reduction in pain score was highest among nonsmokers. Nonsmokers demonstrated a consistent and steady decrease in pain scores over time, whereas the current and former smoker cohorts showed an initial reduction in pain at three months compared to baseline which was not sustained to the 12-months benchmark. Nonetheless, former smokers continued to report slightly lower pain scores than current smokers, although not statistically significant. The baseline opioid consumption was least among nonsmokers (30 [0, 62] oral mg morphine sulfate equivalent). We also found a statistically significant association between time postimplant and reported pain score (χ2 = 508.88, p < 0.001). The overall mean pain score for all three cohorts was highest at baseline (7.6 ± 1.7) and showed a decrease at the 3, 6, and 12 months postimplant time points with mean score of 5.7 ± 2.0, 5.6 ± 2.3, and 5.4 ± 2.5, respectively. CONCLUSION: Tobacco cigarette smoking was associated with reduced SCS effectiveness for pain relief.

Commonalities and differences in abnormal peripheral metabolites between patients with fibromyalgia and complex regional pain syndrome.

Background: Fibromyalgia (FM) and complex regional pain syndrome (CRPS) share many pathological mechanisms related to chronic pain that could contribute to multifactorial pathological mechanisms.Methods: We investigated peripheral metabolites in FM and CRPS patients compared to healthy controls based on cross-sectional study.Results: Mean corpuscular hemoglobin (p < 0.001), mean corpuscular volume (p = 0.014), and total bilirubin levels (p = 0.017) were lower in FM patients than in healthy controls. On the other hand, CRPS patients showed lower levels of total bilirubin than healthy controls (p = 0.037). Creatinine level was lower in FM patients (p = 0.057) compared to healthy controls, particularly when comparing the low-hemoglobin subgroup among FM patients (p = 0.035) with the low-hemoglobin subgroup among healthy controls. Red blood cell count (r = -0.620, p = 0.031), hematocrit (r = -0.593, p = 0.042), and creatinine level (r = -0.598, p = 0.040) showed negative correlations with McGill Pain Questionnaire-Affective (MPQ-A) scores in FM patients. A negative correlation was observed between MCV and McGill Pain Questionnaire-Sensory scores (r = -0.680, p = 0.015) in CRPS patients.Conclusion: We found specific peripheral metabolites that may exhibit different tendency between FM and CRPS patients as well as some common metabolites, which may be associated with peripheral pathology in the patients. Considering this study had a few limitations such as a small sample sizes and using a liberal threshold of significance in the correlation analysis, future studies with larger sample sizes may be needed to generalize these findings.

Influence of vitamin C on the incidence of CRPS-I after subacromial shoulder surgery.

PURPOSE: The primary aim of this study was to determine whether postoperative administration of vitamin C (VC) is associated with reduced risk of complex regional pain syndrome type I (CRPS-I) after subacromial shoulder surgery (SaSS). The secondary objective of the study was to identify risk factor for the development of CRPS-I after SaSS. MATERIALS AND METHODS: A retrospective cohort study was performed to evaluate 542 patients undergoing SaSS from January 2015 to December 2016. The cohort was divided into two groups based on VC administration [Group I (no VC) and Group II (500 mg/day oral VC for 50 days postoperatively)]. The relationship between VC administration and development of CRPS-I was assessed. Demographics, preoperative clinical parameters, and operative variables were evaluated to determine their effect on the incidence of CRPS-I. RESULTS: A total of 267 patients (Group II) undergoing SaSS received VC, and 266 patients (Group I) did not. The incidence of CRPS-I was significantly different between two groups (36(13%) vs 18(7%), p = 0.009). Multivariable regression, however, demonstrated that VC reduced the risk of CRPS-I after SaSS by > 50% (aOR = 0.49; 95% CI 0.27-0.91). Patients undergoing open surgery (aOR = 2.19; 95% CI 1.2-4.0) were more likely to develop CRPS-I postoperatively. Higher preoperative Constant score (aOR = 0.94; 95% CI 0.91-0.98) was associated with lower risk for CRPS-I development. CONCLUSIONS: The present study found that VC administered prophylactically for 50 days postoperatively is effective in preventing CRPS-I development after SaSS. CRPS-I is a common complication following SaSS, especially in the setting of an open approach. The authors recommend preventive management with VC and arthroscopic approaches when possible for SaSS. LEVEL OF EVIDENCE III: Retrospective comparative study.

Randomized Placebo-/Sham-Controlled Trials of Spinal Cord Stimulation: A Systematic Review and Methodological Appraisal.

OBJECTIVES: The recent availability of paraesthesia/sensation free spinal cord stimulation (SCS) modalities allow the design of clinical trials of SCS using placebo/sham controls and blinding of patients, clinicians, and researchers. The aims of this study were to: 1) systematically review the current evidence base of randomized controlled trials (RCTs) of SCS placebo/sham trials and 2) to undertake a methodological critique of their methods. Based on this critique, we developed a checklist for the design and reporting of future RCTs of SCS. MATERIALS AND METHODS: Electronic data bases were searched from inception until January 2019 for RCTs of SCS using a placebo/sham control. RCTs with only an active comparator arm were excluded. The results are presented as a narrative synthesis. RESULTS: Searches identified 12 eligible RCTs. SCS modalities included paraesthesia stimulation, subthreshold, burst, and high-frequency SCS and were mainly conducted in patients with failed back surgery syndrome, complex regional pain syndrome, and refractory angina. The quality and transparency of reporting of the methods of placebo stimulation, blinding of patients, clinicians, and researchers varied markedly across studies. CONCLUSIONS: To date the methods of placebo/sham control and blinding in RCTs have been poorly reported, leading to concerns about the validity and replicability of the findings. Important aspects that need to be clearly reported in the design of placebo-/sham-controlled RCTs of SCS include the transparent reporting of stimulation programming parameters, patient position during perception threshold measurement, management of the patient handheld programmer, frequency of recharging, and assessment of the fidelity of blinding.