Effects of Rhythmic Sensory Stimulation on Ehlers-Danlos Syndrome: A Pilot Study.

Ehlers-Danlos syndrome (EDS) is a connective tissue disorder characterized by joint hypermobility and skin extensibility and is often accompanied by chronic pain. Rhythmic sensory stimulation (RSS) can be defined as the stimulation of the senses in a periodic manner within a range of low frequencies. Music plus sound delivered through a vibroacoustic device is a form of RSS and has demonstrated utility in managing pain. In this current study, we conducted an open-label pilot study of 15 patients with hypermobile EDS using RSS as the intervention. Posttreatment improvements were seen in 11 of the 15 patients (73%), whereas 3 of the 15 patients (20%) experienced worse outcomes. Of the 14 patients that completed the experiment, 6 participants (43%) were classified as "responders" to the device while 8 participants (57%) were classified as "nonresponders." Responders demonstrated significant improvements in pain interference (51.5 ± 16 preintervention vs. 43.5 ± 16.4 postintervention BPI score) and depression symptoms (34.0 ± 15.9 preintervention vs. 26.8 ± 12.1 postintervention CESD score). Poststudy interviews confirm the improvements of pain interference, mood, and bowel symptoms. Furthermore, analysis of medical conditions within the responder group indicates that the presence of depression, anxiety, irritable bowel syndrome, and fibromyalgia may indicate a greater likelihood for patients to benefit with vibroacoustic applications. These results indicate a possible potential for RSS, delivered using a vibroacoustic device, in managing pain-related symptoms. Further research is necessary to elucidate the exact mechanism behind the physiological benefits of RSS.

A parallel randomized controlled trial examining the effects of rhythmic sensory stimulation on fibromyalgia symptoms.

This double-blind, two-arm parallel randomized controlled trial investigated the effects of gamma-frequency rhythmic sensory stimulation on fibromyalgia. We were interested in whether rhythmic sensory stimulation would promote significant changes in fibromyalgia and associated symptoms, and whether treatment effects would differ between two distinct treatment parameters. Fifty patients with a formal diagnosis of fibromyalgia were randomly assigned to two test groups. One group received vibrotactile stimulation from a continuous sine wave single-frequency stimulation (40 Hz) for 30 minutes, five days per week, over five weeks, concomitant with usual care. The second group completed the same treatment protocol but received a different stimulation, consisting of random and intermittent complex wave gamma-range vibrotactile stimulation. Fibromyalgia symptoms, pain severity and interference, depression symptoms, quality of life and sleep quality were assessed at baseline and post-intervention. Results indicated that there were statistically significant changes from baseline to post-treatment in measures of fibromyalgia symptom severity, pain interference, depression, and sleep quality. However, treatment outcomes did not differ significantly between groups. These findings provide preliminary evidence that gamma-frequency rhythmic vibroacoustic stimulation may decrease fibromyalgia symptoms and ease associated comorbidities, opening new avenues for further investigation of the effects of rhythmic sensory stimulation on chronic pain conditions.

Long-Term Outcomes in the Management of Central Neuropathic Pain Syndromes: A Prospective Observational Cohort Study.

BACKGROUND: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, traumatic spinal cord injury, or multiple sclerosis. These syndromes are distinctly less common than peripheral neuropathic pain, and less is known regarding the underlying pathophysiology, appropriate pharmacotherapy, and long-term outcomes. The objective of this study was to determine the long-term clinical effectiveness of the management of central neuropathic pain relative to peripheral neuropathic pain at tertiary pain centers. METHODS: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified for analysis from a prospective observational cohort study of patients with chronic neuropathic pain recruited from seven Canadian tertiary pain centers. Data regarding patient characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome measure was the composite of a reduction in average pain intensity and pain interference. Secondary outcome measures included assessments of function, mood, quality of life, catastrophizing, and patient satisfaction. RESULTS: At 12-month follow-up, 13.5% (95% confidence interval [CI], 5.6-25.8) of patients with central neuropathic pain and complete data sets (n=52) achieved a ≥30% reduction in pain, whereas 38.5% (95% CI, 25.3-53.0) achieved a reduction of at least 1 point on the Pain Interference Scale. The proportion of patients with central neuropathic pain achieving both these measures, and thus the primary outcome, was 9.6% (95% CI, 3.2-21.0). Patients with peripheral neuropathic pain and complete data sets (n=463) were more likely to achieve this primary outcome at 12 months (25.3% of patients; 95% CI, 21.4-29.5) (p=0.012). CONCLUSION: Patients with central neuropathic pain syndromes managed in tertiary care centers were less likely to achieve a meaningful improvement in pain and function compared with patients with peripheral neuropathic pain at 12-month follow-up.

An Online Cross-Sectional Comparison of Women With Symptoms of Persistent Genital Arousal, Painful Persistent Genital Arousal, and Chronic Vulvar Pain.

BACKGROUND: Persistent genital arousal disorder (PGAD) is an understudied condition characterized by unwanted physiologic genital arousal in the absence of subjective sexual arousal. Markos and Dinsmore (Int J STD AIDS 2013;24:852-858) theorized that PGAD shares a number of similarities with vulvodynia (unexplained chronic vulvar pain [CVP]), including symptom characteristics and comorbidities. AIM: To compare medical histories, symptom characteristics, pain characteristics, and daily functioning among women with persistent genital pain (PGA) (n = 42), painful PGA (n = 37), and CVP (n = 42) symptoms. METHODS: An online cross-sectional survey was conducted from October 2015 through April 2016. OUTCOMES: Self-report measures of symptoms, diagnosed medical conditions, pain characteristics (McGill Pain Questionnaire), catastrophizing (Pain Catastrophizing Scale), and daily functioning (Functional Status Questionnaire) were collected. RESULTS: All 3 groups reported similar medical diagnoses and high frequencies of other chronic pelvic pain conditions. Women in all 3 groups reported comparable ages at symptom onset and timing of symptom expression (ie, constant vs intermittent). Women in the 2 PGA groups reported significantly greater feelings of helplessness than women in the CVP group. Women in the painful PGA and CVP groups endorsed significantly more sensory terms to describe their symptoms compared with women in the PGA group, whereas women in the painful PGA group reported significantly more affective terms to describe their symptoms compared with women in the CVP group. Women in the 2 PGA groups reported that their symptoms interfered significantly with most areas of daily functioning. CLINICAL IMPLICATIONS: Given the similarities between PGA and CVP symptoms, women with PGA may benefit from similar assessment, treatment, and research approaches. STRENGTHS AND LIMITATIONS: Limitations of the present study include its sole use of self-report measures; the presence of PGA or CVP symptoms was not confirmed by clinical assessment. However, the anonymous design of the online survey could have resulted in a larger and more diverse sample. CONCLUSION: The results of this study provide some initial support for the conceptualization of persistent genital arousal as a subtype of genital paresthesias/discomfort. These results also further highlight the negative impact that PGA symptoms have on many domains of daily living and the need for further research on this distressing condition. Jackowich RA, Pink L, Gordon A, et al. An Online Cross-Sectional Comparison of Women With Symptoms of Persistent Genital Arousal, Painful Persistent Genital Arousal, and Chronic Vulvar Pain. J Sex Med 2018;15:558-567.

Chronic scrotal pain may lead to reduced sexual function and interest, while sexual activity may worsen chronic scrotal pain: "double jeopardy".

BACKGROUND: While it is recognized that chronic pain may adversely impact sexual function and activity in men and we also recognize that sexual activity may worsen the pain for men with chronic scrotal pain (CSP), the effect on sexual functioning and conversely the impact of sex on CSP has not previously been documented. METHODS: Retrospective analysis of a prospectively collected database. RESULTS: From Feb 2014 to Sep 2015, a total of 128 men presenting for assessment of CSP completed all or parts of a standardized questionnaire. Overall 60% (69/116) of the men felt that the CSP had kept them either a "lot" or "some" of the time from sexual activity and 64% (27/43) had evidence of decreased erectile performance. Those with more severe pain (analog pain scores 7-10/10) had more significant sexual dysfunction than those with less severe pain, with 54% (45/83) vs. 0% (0/33, P<0.01: Fisher's exact test) noting that the pain kept them from sexual activity "a lot" and 70% (23/33) vs. 40% (4/10, P<0.01) noting sexual dysfunction. Diminished libido was also common in the men [43% (55/128)] as were the symptoms of testosterone deficiency [76% (97/128)]. Conversely, sexual activity often exacerbated the pain, with 37% (47/128) finding that ejaculation aggravated their pain and another 38% (48/128) patients found sexual activity aggravated their pain. CONCLUSIONS: Men with severe CSP have significantly reduced sexual function and interest compared to men with moderate or minor levels of pain. The majority of men with CSP who were sexually active were faced with worsening pain with sex and ejaculation. Clinicians should be aware of the twin risks of sexual dysfunction occurring in men with CSP and sexual activity worsening the severity of the CSP.

Sensitivity of the DN4 in Screening for Neuropathic Pain Syndromes.

OBJECTIVES: Several tools have been developed to screen for neuropathic pain. This study examined the sensitivity of the Douleur Neuropathique en 4 Questions (DN4) in screening for various neuropathic pain syndromes. MATERIALS AND METHODS: This prospective observational study was conducted in 7 Canadian academic pain centers between April 2008 and December 2011. All newly admitted patients (n=2199) were approached and 789 eligible participants form the sample for this analysis. Baseline data included demographics, disability, health-related quality of life, and pain characteristics. Diagnosis of probable or definite neuropathic pain was on the basis of history, neurological examination, and ancillary diagnostic tests. RESULTS: The mean age of study participants was 53.5 years and 54.7% were female; 83% (n=652/789) screened positive on the DN4 (≥4/10). The sensitivity was highest for central neuropathic pain (92.5%, n=74/80) and generalized polyneuropathies (92.1%, n=139/151), and lowest for trigeminal neuralgia (69.2%, n=36/52). After controlling for confounders, the sensitivity of the DN4 remained significantly higher for individuals with generalized polyneuropathies (odds ratio [OR]=4.35; 95% confidence interval [CI]: 2.15, 8.81), central neuropathic pain (OR=3.76; 95% CI: 1.56, 9.07), and multifocal polyneuropathies (OR=1.72; 95% CI: 1.03, 2.85) compared with focal neuropathies. DISCUSSION: The DN4 performed well; however, sensitivity varied by syndrome and the lowest sensitivity was found for trigeminal neuralgia. A positive DN4 was associated with greater pain catastrophizing, disability and anxiety/depression, which may be because of disease severity, and/or these scales may reflect magnification of sensory symptoms and findings. Future research should examine how the DN4 could be refined to improve its sensitivity for specific neuropathic pain conditions.

Symptom Characteristics and Medical History of an Online Sample of Women Who Experience Symptoms of Persistent Genital Arousal.

Persistent genital arousal disorder (PGAD; Leiblum & Nathan, 2001 ) is characterized by distressing symptoms suggestive of genital arousal in the absence of subjective feelings of arousal. Although awareness of PGAD is growing, there continues to be a lack of systematic research on it. This study characterized an online sample of women with symptoms of persistent genital arousal (PGA) in terms of their symptom characteristics, medical comorbidities, symptom triggers, management strategies, and predictors of distress. Women reported diverse PGA symptoms, with almost half reporting painful symptoms, and most reported very high distress and negative emotions. Further research and awareness of PGA are needed to provide effective care for this population.

How are perceptions associated with water consumption in Canadian Inuit? A cross-sectional survey in Rigolet, Labrador.

Concerns regarding the safety and aesthetic qualities of one's municipal drinking water supply are important factors influencing drinking water perceptions and consumption patterns (i.e. sources used and daily volume of consumption). In northern Canada, Inuit communities face challenges with drinking water quality, and many Inuit have reported concerns regarding the safety of their drinking water. The objectives of this research were to describe perceptions of municipal tap water, examine use of water sources and changes following the installation of a potable water dispensing unit (PWDU) in 2014, and identify factors associated with water consumption in the Inuit community of Rigolet. This study used data from three cross-sectional census surveys conducted between 2012 and 2014. Principal component analysis (PCA) was used to aggregate data from multiple variables related to perceptions of water, and logistic regressions were used to identify variables associated with water consumption patterns. Three quarters of residents reported using the PWDU after its installation, with concomitant declines reported in consumption of bottled, tap, and brook water. Negative perceptions of tap water were associated with lower odds of consuming tap water (ORPCAcomponent1=0.73, 95% CI 0.56-0.94; ORPCAcomponent2=0.67, 95% CI 0.49-0.93); women had higher odds of drinking purchased water compared to men (OR=1.90, 95% CI 1.11-3.26). The median amount of water consumed per day was 1L. Using brook water (OR=2.60, 95% CI 1.22-5.56) and living in a household where no one had full-time employment (OR=2.94, 95% CI 1.35-6.39) were associated with consuming >2L of water per day. Results of this study may inform drinking water interventions, risk assessments, and public health messaging in Rigolet and other Indigenous communities.

Self-management of cardiac pain in women: an evidence map.

OBJECTIVE: To describe the current evidence related to the self-management of cardiac pain in women using the process and methodology of evidence mapping. DESIGN AND SETTING: Literature search for studies that describe the self-management of cardiac pain in women greater than 18 years of age, managed in community, primary care or outpatient settings, published in English or a Scandinavian language between 1 January 1990 and 24 June 2016 using AMED, CINAHL, ERIC, EMBASE, MEDLINE, Proquest, PsychInfo, the Cochrane Library, Scopus, Swemed+, Web of Science, the Clinical Trials Registry, International Register of Controlled Trials, MetaRegister of Controlled Trials, theses and dissertations, published conference abstracts and relevant websites using GreyNet International, ISI proceedings, BIOSIS and Conference papers index. Two independent reviewers screened using predefined eligibility criteria. Included articles were classified according to study design, pain category, publication year, sample size, per cent women and mean age. INTERVENTIONS: Self-management interventions for cardiac pain or non-intervention studies that described views and perspectives of women who self-managed cardiac pain. PRIMARY AND SECONDARY OUTCOMES MEASURES: Outcomes included those related to knowledge, self-efficacy, function and health-related quality of life. RESULTS: The literature search identified 5940 unique articles, of which 220 were included in the evidence map. Only 22% (n=49) were intervention studies. Sixty-nine per cent (n=151) of the studies described cardiac pain related to obstructive coronary artery disease (CAD), 2% (n=5) non-obstructive CAD and 15% (n=34) postpercutaneous coronary intervention/cardiac surgery. Most were published after 2000, the median sample size was 90 with 25%-100% women and the mean age was 63 years. CONCLUSIONS: Our evidence map suggests that while much is known about the differing presentations of obstructive cardiac pain in middle-aged women, little research focused on young and old women, non-obstructive cardiac pain or self-management interventions to assist women to manage cardiac pain. PROSPERO REGISTRATION NUMBER: CRD42016042806.

Attenuation of Insulin Action by an Allosteric Insulin Receptor Antibody in Healthy Volunteers.

Background: XOMA 358 (X358) is a fully human monoclonal antibody to the insulin receptor that acts as a negative allosteric modulator of insulin signaling. It is being developed as a novel treatment of hyperinsulinemic hypoglycemia. This report describes pharmacokinetic (PK) and pharmacodynamic (PD) data from a first-in-human clinical trial. Methods: A double-blind, placebo-controlled, single-ascending-dose study was performed with 29 healthy adult males randomized to intravenous infusion of placebo or X358 at 0.1-, 0.3-, 1-, 3-, 6-, or 9-mg/kg dose levels. The primary objective was to assess safety and tolerability, and secondary objectives included PK and PD analyses. A short insulin tolerance test (ITT) was implemented in the 3- to 9-mg/kg dose cohorts at baseline and postinfusion. Results: There were no deaths, serious adverse events (AEs), or subject discontinuations due to AEs. There were no clinically meaningful safety findings. X358 exhibited dose-proportional PK with a half-life of 21 days. Dose-dependent elevations of circulating insulin levels, likely related to reduced insulin clearance via monoclonal antibody action at receptors, represented a sensitive biomarker of X358 exposure. X358-dependent increases in postprandial glucose levels and fasting homeostatic model assessment of insulin resistance values were observed and persisted for at least 1 week at the higher dose levels. In all the ITT cohorts, the slope for glucose lowering was substantially attenuated after X358 infusion of a similar magnitude, but with increasing duration with rising dose level. Conclusion: Single X358 infusions were well tolerated and resulted in a dose-dependent reduction in insulin sensitivity. Clinical development of X358 in hyperinsulinemic, hypoglycemic conditions is proceeding.

Characteristics and Etiologies of Chronic Scrotal Pain: A Common but Poorly Understood Condition.

Chronic scrotal pain (CSP) is a common and debilitating condition, but the underlying characteristics and etiology of CSP are poorly understood. The objective of this study is to identify the characteristic and etiologies of CSP. Men presenting for management of CSP completed a standardized questionnaire and underwent a complete physical examination. From Feb 2014 to Sep 2015, a total of 131 men (mean age 43) with CSP were studied. The CSP was of long duration (mean of 4.7 ± 5.95 years) and dramatically affected men's lives, with adverse effects on normal activities (71.%), ability to work (51.90%), and sexual functioning (61.8%). 50.4% felt depressed on most days, and 67.17% felt either unhappy or terrible with their present condition. Physical examination revealed that the epididymis was the most common tender area found in 70/131 men (53.43%), though a musculoskeletal source for the pain was found in 9.9%. Neuropathic changes were found in 30%. For close to half of the men (43.5%) we were unable to identify any potential cause for the CSP. This study characterizes the dramatic impact that CSP has on the lives of men, while providing an understanding of the common etiologies.

Long-Term Outcomes in the Management of Painful Diabetic Neuropathy.

BACKGROUND: Painful diabetic neuropathy (PDN) is a frequent complication of diabetes mellitus. Current treatment recommendations are based on short-term trials, generally of ≤3 months' duration. Limited data are available on the long-term outcomes of this chronic disease. The objective of this study was to determine the long-term clinical effectiveness of the management of chronic PDN at tertiary pain centres. METHODS: From a prospective observational cohort study of patients with chronic neuropathic non-cancer pain recruited from seven Canadian tertiary pain centres, 60 patients diagnosed with PDN were identified for analysis. Data were collected according to Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials guidelines including the Brief Pain Inventory. RESULTS: At 12-month follow-up, 37.2% (95% confidence interval [CI], 23.0-53.3) of 43 patients with complete data achieved pain reduction of ≥30%, 51.2% (95% CI, 35.5-66.7) achieved functional improvement with a reduction of ≥1 on the Pain Interference Scale (0-10, Brief Pain Inventory) and 30.2% (95% CI, 17.2-46.1) had achieved both these measures. Symptom management included at least two medication classes in 55.3% and three medication classes in 25.5% (opioids, antidepressants, anticonvulsants). CONCLUSIONS: Almost one-third of patients being managed for PDN in a tertiary care setting achieve meaningful improvements in pain and function in the long term. Polypharmacy including analgesic antidepressants and anticonvulsants were the mainstays of effective symptom management.

Frequency and severity of chronic scrotal pain in Canadian men presenting to urologists for infertility investigations.

BACKGROUND: Chronic scrotal pain (CSP) may be debilitating in men presenting for treatment for CSP, but we have little information on the frequency and severity of CSP in the men who do not seek care for the CSP. Our objective was to identify the frequency and characteristics of CSP in a population of men presenting for reasons other than CSP to a urology clinic. METHODS: Men presenting to a urology clinic for investigation of male infertility (INF) completed a standardized CSP questionnaires if they self-reported having CSP. This prospectively collected database was then retrospectively analyzed. RESULTS: Forty-five of 1,203 (3.7%) of INF patients (mean age 35: range, 24-59), reported having CSP (INF/CSP). Our comparison group was 131 men presenting for investigation of CSP [mean age 43¡À12 (SD) years with a mean duration of CSP of 4.7¡À5.95 years]. On average, men with INF/CSP had less severe and frequent pain than those with CSP, with significantly less pain during "bad" pain episodes (5.2¡À2.2 vs. 7.4¡À2.1, VAS score 0-10, P<0.0001 Student's t-test), less frequent "bad" pain episodes (23%¡À21% vs. 42%¡À30% of the time, P<0.0001 Student's t-test) and lower proportion of men who reported having severe pain (VAS score 7-10/10) (4/45 vs. 46/131, P<0.001, chi-squared test). Both groups reported a negative impact of the pain on quality of life (QOL), with 60% and 86% of men with INF/CSP and CSP alone reporting that they would feel 'mostly dissatisfied', 'unhappy', or 'terrible' if they had to continue life with their present scrotal pain symptoms. CONCLUSIONS: Clinicians should be aware that CSP is common among men presenting for conditions other than CSP and that even if the pain levels are not "severe", the chronic pain often has a significant negative impact on QOL.

Quality of life in men with chronic scrotal pain.

Background: Chronic scrotal pain (CSP) is a common and often debilitating condition found in up to 4.75% of men. There is little written on the impact of CSP on men's lives. Aim: The aim of this study was to understand the impact of CSP on men's lives. Methods: Patients with CSP were prospectively asked to complete a comprehensive questionnaire, including questions on quality of life (QoL), activities, and mood. Results: The mean age of the 131 patients was 43 years. Pain was intermittent, with severe pain episodes (mean pain scores 7.2 ± 2 out of 10) affecting men on average 40% ± 30% of the time. Overall, 88/131 (67.17%) of patients responded that they felt "unhappy" or "terrible" with their present situation. More than 40% of patients complained of depressive symptoms more than half the days of the month. Normal activities were adversely affected, with 68/131 (51.90%) reporting limited ability to work, 93/131 (70.99%) patients reporting decreased physical activity, and 81/131(61.83%) reporting decreased sexual activity. Comparing men with pain levels ≥ 7/10 vs. those with pain levels < 7/10, 47% (41/88) vs. 8.1% (3/37) reported that they felt "terrible," 40% (35/88) vs. 13% (5/38) had depressive feelings more than half the time, and 35% (28/80) vs. 16% (6/38) felt little pleasure doing things (P < 0.01 for all). Conclusion: Our study suggests that QoL, mood, and the ability to perform normal activities are profoundly disturbed in CSP patients and that the pain severity is directly related to QoL.

Contexte: La douleur scrotale chronique est une affection commune et souvent débilitante dont souffrent près de 4,75 % des hommes. Il y a peu d'écrits sur l'impact de la douleur scrotale chronique sur la vie des hommes.But: Comprendre l'impact de la douleur scrotale chronique sur la vie des hommes.Méthodes: On a demandé de manière prospective à des patients souffrant de douleur scrotale chronique de remplir un questionnaire détaillé comprenant des questions sur leur qualité de vie, leurs activités et leur humeur.Résultats: L'âge moyen des 131 patients était de 43 ans. La douleur était intermittente, comportait des épisodes de douleur intense (scores de la douleur moyens 7,2 +/- 2 sur 10) et affectait les hommes 40 % +/- 30 % du temps. Globalement, 88/131 (67,17 %) des patients ont répondu qu'ils se sentaient malheureux ou « horriblement mal ¼ en raison de leur situation actuelle. Plus de 40 % des patients se sont plaints de symptômes de dépression plus de la moitié des jours du mois. Leurs activités habituelles étaient affectées négativement, alors que 68/131 (51,90 %) disaient avoir une capacité de travail limitée, que 93/131 (70,99 %) des patients signalaient une diminution de leur activité physique et que 81/131 (61,83 %) d'entre eux faisaient état d'une diminution de leur activité sexuelle. La comparaison des hommes qui avaient un niveau de douleur ≥ 7/10 à ceux qui avaient un niveau de douleur < 7/10 a révélé que 47 % d'entre eux (41/88) se sentaient « horriblement pas bien ¼ contre 8,1 % (3/37), que 40 % (35/88) avaient des sentiments dépressifs plus de la moitié du temps contre 13 % (5/38) et que 35 % (28/80) ressentaient peu de plaisir à faire les choses contre 16 % (6/38) (p < 0,01 pour tous).Conclusion: Notre étude suggère que la qualité de vie, l'humeur et la capacité à vaquer à ses activités habituelles sont profondément perturbées chez les patients qui souffrent de douleur scrotale chronique et que l'intensité de la douleur est directement liée à la qualité de vie.

Perineural steroid injections around ilioinguinal, iliohypogastric, and genitofemoral nerves for treatment of chronic refractory neuropathic pain: A retrospective study.

Background: Perineural local anaesthetic and steroid injections around ilioinguinal (II), iliohypogastric (IH), and genitofemoral (GF) nerves are often performed to treat chronic refractory neuropathic pain in the lower abdomen and groin, but there is a lack of published data on outcomes of these interventions. Aims: The objective of this retrospective study was to evaluate analgesic outcomes of ultrasound-guided II, IH, and GF nerve blocks in patients with chronic neuropathic pain in the lower abdominal wall and groin. Methods: Analgesic outcomes were assessed at 6 weeks after injections and patients were classified as "responders" if the numerical rating scale for pain score reduced by 30% or more. Variables analyzed for impact on outcomes included demographics, intensity of pain and duration, etiology, dose of opioid, presence of anxiety, depression, and diabetes mellitus. Results: In this cohort of 54 patients with severe baseline pain who had failed to receive analgesic benefit from recommended first- and second-line medications for neuropathic pain, 30 patients had history of surgery and 24 had pain secondary to visceral inflammatory pathologies. Twenty-five (46.3%) patients were identified as responders. A majority of the patients in this cohort had pain for more than one year. There was a higher incidence of diabetes mellitus in nonresponders compared to responders but the difference was not significant (14% and 0%, respectively; P = 0.115). Conclusions: Ultrasound-guided perineural steroids can ameliorate chronic refractory abdominal wall and groin neuropathic pain in patients who have failed to respond to conventional medical management at 6 weeks after the procedures.

Contexte: L'anesthésie locorégionale périneurale et les injections de stéroïdes à proximité du nerf ilio-inguinal (II), du nerf ilio-hypogastrique (IH) et du nerf génito-fémoral (GF) sont souvent utilisées pour traiter la douleur neuropathique chronique réfractaire dans le bas-ventre et dans l'aine, mais peu de données ont été publiées sur les résultats de ces interventions.But: L'objectif de cette étude rétrospective était d'évaluer les résultats analgésiques du blocage des nerfs II, IH et GF guidé par ultrasons chez des patients souffrant de douleur neuropathique chronique dans la paroi du bas-ventre et dans l'aine.Méthodes: Les résultats analgésiques ont été évalués six semaines après les injections et les patients ont été classés « répondeurs ¼ si le score obtenu sur l'échelle numérique pour la douleur avait diminué de 30 % ou plus. Les variables analysées pour leur effet sur les résultats comprenaient les données démographiques; l'intensité et la durée de la douleur; l'étiologie; le dose d'opiacés, la présence d'anxiété; la dépression; et le diabète sucré.Résultats: Parmi cette cohorte de 54 patients souffrant d'une douleur sévère au départ pour lesquels les médications de première et de deuxième ligne recommandées pour la douleur neuropathique n'avaient pas été bénéfiques, 30 patients avaient une histoire de chirurgie et 24 avaient des douleurs secondaires à des pathologies inflammatoires viscérales. 25 patients (46,3 %) ont été identifiés comme répondants. La majorité des patients de cette cohorte ressentaient de la douleur depuis plus d'un an. Il y avait une plus grande incidence de diabète sucré chez les non-répondeurs comparativement aux répondeurs mais la différence n'était pas significative (14 % et 0 % respectivement; p = 0,115).Conclusions: Les stéroïdes périneuraux guidés par ultrasons peuvent améliorer la douleur neuropathique chronique réfractaire dans la paroi abdominale et dans l'aine chez les patients qui n'ont pas répondu à la prise en charge médicale conventionnelle six semaines après les procédures.

Community-based adaptation research in the Canadian Arctic.

Community-based adaptation (CBA) has emerged over the last decade as an approach to empowering communities to plan for and cope with the impacts of climate change. While such approaches have been widely advocated, few have critically examined the tensions and challenges that CBA brings. Responding to this gap, this article critically examines the use of CBA approaches with Inuit communities in Canada. We suggest that CBA holds significant promise to make adaptation research more democratic and responsive to local needs, providing a basis for developing locally appropriate adaptations based on local/indigenous and Western knowledge. Yet, we argue that CBA is not a panacea, and its common portrayal as such obscures its limitations, nuances, and challenges. Indeed, if uncritically adopted, CBA can potentially lead to maladaptation, may be inappropriate in some instances, can legitimize outside intervention and control, and may further marginalize communities. We identify responsibilities for researchers engaging in CBA work to manage these challenges, emphasizing the centrality of how knowledge is generated, the need for project flexibility and openness to change, and the importance of ensuring partnerships between researchers and communities are transparent. Researchers also need to be realistic about what CBA can achieve, and should not assume that research has a positive role to play in community adaptation just because it utilizes participatory approaches. WIREs Clim Change 2016, 7:175-191. doi: 10.1002/wcc.376 For further resources related to this article, please visit the WIREs website.

Data on gene and protein expression changes induced by apabetalone (RVX-208) in ex vivo treated human whole blood and primary hepatocytes.

Apabetalone (RVX-208) inhibits the interaction between epigenetic regulators known as bromodomain and extraterminal (BET) proteins and acetyl-lysine marks on histone tails. Data presented here supports the manuscript published in Atherosclerosis "RVX-208, a BET-inhibitor for Treating Atherosclerotic Cardiovascular Disease, Raises ApoA-I/HDL and Represses Pathways that Contribute to Cardiovascular Disease" (Gilham et al., 2016) [1]. It shows that RVX-208 and a comparator BET inhibitor (BETi) JQ1 increase mRNA expression and production of apolipoprotein A-I (ApoA-I), the main protein component of high density lipoproteins, in primary human and African green monkey hepatocytes. In addition, reported here are gene expression changes from a microarray-based analysis of human whole blood and of primary human hepatocytes treated with RVX-208.

Persistent Genital Arousal Disorder: A Review of Its Conceptualizations, Potential Origins, Impact, and Treatment.

INTRODUCTION: Persistent genital arousal disorder (PGAD) is a condition characterized by symptoms of physiologic (typically genital) sexual arousal in the absence of perceived subjective sexual arousal. The physiologic arousal can last hours or days, or it can occur constantly, and it does not typically remit after orgasm(s). The symptoms are usually described as distressing, intrusive, and unwanted. AIM: To review the available literature on PGAD. METHODS: A literature review through April 2016 was undertaken using terms persistent genital arousal disorder, persistent sexual arousal syndrome, and restless genital syndrome. MAIN OUTCOME MEASURES: The main outcome is a review of the conceptualization of PGAD, its prevalence, proposed etiologies and treatments, and its impact on psychosocial and sexual functioning. RESULTS: Much of the research on the potential etiologies and treatments of PGAD is published in the form of case studies. Several etiologies of PGAD have been proposed; however, a cause or causes have not been confirmed. A range of treatments has been explored primarily in case studies, from electroconvulsive therapy to oral medication, with variable success rates. Psychologically based treatments have been suggested but have yet to be evaluated. Online surveys have found initial evidence supporting the negative impact of PGAD on mental health and sexual functioning; however, more research is needed in this area. CONCLUSION: Although PGAD was first conceptualized 15 years ago, it remains a very under-researched condition. Currently, little is known about its biopsychosocial correlates, etiologies, or successful treatments. Future research directions are identified.

Effects of the BET-inhibitor, RVX-208 on the HDL lipidome and glucose metabolism in individuals with prediabetes: A randomized controlled trial.

AIMS: High-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I) can modulate glucose metabolism through multiple mechanisms. This study determined the effects of a novel bromodomain and extra-terminal (BET) inhibitor (RVX-208) and putative apoA-I inducer on lipid species contained within HDL (HDL lipidome) and glucose metabolism. MATERIALS AND METHODS: Twenty unmedicated males with prediabetes received 100mg b.i.d. RVX-208 and placebo for 29-33days separated by a wash-out period in a randomized, cross-over design trial. Plasma HDL-cholesterol and apoA-I were assessed as well as lipoprotein particle size and distribution using NMR spectroscopy. An oral glucose tolerance test (OGTT) protocol with oral and infused stable isotope tracers was employed to assess postprandial plasma glucose, indices of insulin secretion and insulin sensitivity, glucose kinetics and lipolysis. Whole plasma and HDL lipid profiles were measured using mass spectrometry. RESULTS: RVX-208 treatment for 4weeks increased 6 sphingolipid and 4 phospholipid classes in the HDL lipidome (p≤0.05 versus placebo), but did not change conventional clinical lipid measures. The concentration of medium-sized HDL particles increased by 11% (P=0.01) and small-sized HDL particles decreased by 10% (P=0.04) after RVX-208 treatment. In response to a glucose load, after RVX-208 treatment, plasma glucose peaked at a similar level to placebo, but 30min later with a more sustained elevation (treatment effect, P=0.003). There was a reduction and delay in total (P=0.001) and oral (P=0.003) glucose rates of appearance in plasma and suppression of endogenous glucose production (P=0.014) after RVX-208 treatment. The rate of glucose disappearance was also lower following RVX-208 (P=0.016), with no effect on glucose oxidation or total glucose disposal. CONCLUSIONS: RVX-208 increased 10 lipid classes in the plasma HDL fraction, without altering the concentrations of either apoA-I or HDL-cholesterol (HDL-C). RVX-208 delayed and reduced oral glucose absorption and endogenous glucose production, with plasma glucose maintained via reduced peripheral glucose disposal. If sustained, these effects may protect against the development of type 2 diabetes.