Complex Regional Pain Syndrome in Cancer Cases: Current Knowledge and Perspectives.

Background: Complex regional pain syndrome (CRPS) is a disabling painful disorder caused by many different and poorly understood mechanisms. It often affects the distal limbs and usually happens as consequence of a trauma. Its severity can remarkably affect patients' quality of life. When this painful complication happens in a cancer patient, the impact may be exponential. To date, there is limited knowledge of the surrounding circumstances of CRPS cases in this population. Methods: We present two clinical cases of patients diagnosed with cancer-related pain presenting with symptoms and signs compatible with CRPS. In one case, CRPS was attributed to direct tumor nerve compression, and it responded successfully to an interventional pain procedure. The second case was associated with a Zoster infection in an immunocompromised cancer patient. Patient responded to multidisciplinary pain management strategies. Additionally, we conducted a literature review to investigate the coexistence of cancer pain and CRPS and suggest some pathophysiology mechanisms of action. Results and Discussion: Literature reviewed and potential pathophysiology mechanisms are simultaneously explored in terms of classification, etiopathology, evidence, challenges, and future scientific directions. Conclusion: Comorbid CRPS can impact negatively in cases of cancer pain by affecting their diagnosis and treatment. Further studies are necessary to elucidate how these two conditions present together and how they can be better addressed.

A prognostic risk score for development and spread of chronic pain.

Chronic pain is a complex condition influenced by a combination of biological, psychological and social factors. Using data from the UK Biobank (n = 493,211), we showed that pain spreads from proximal to distal sites and developed a biopsychosocial model that predicted the number of coexisting pain sites. This data-driven model was used to identify a risk score that classified various chronic pain conditions (area under the curve (AUC) 0.70-0.88) and pain-related medical conditions (AUC 0.67-0.86). In longitudinal analyses, the risk score predicted the development of widespread chronic pain, the spreading of chronic pain across body sites and high-impact pain about 9 years later (AUC 0.68-0.78). Key risk factors included sleeplessness, feeling 'fed-up', tiredness, stressful life events and a body mass index >30. A simplified version of this score, named the risk of pain spreading, obtained similar predictive performance based on six simple questions with binarized answers. The risk of pain spreading was then validated in the Northern Finland Birth Cohort (n = 5,525) and the PREVENT-AD cohort (n = 178), obtaining comparable predictive performance. Our findings show that chronic pain conditions can be predicted from a common set of biopsychosocial factors, which can aid in tailoring research protocols, optimizing patient randomization in clinical trials and improving pain management.

Early Interventional Treatments for Patients with Cancer Pain: A Narrative Review.

Between 10% and 20% of patients with cancer-related pain cannot achieve adequate control following the three-step ladder guidelines by the World Health Organization. Therefore, a "fourth step", including interventional approaches, has been suggested for those cases. Systematic reviews support the early use of interventional procedures to treat refractory cancer pain, control symptoms and prevent opioid dose escalation. There is strong evidence of the efficacy of celiac plexus or splanchnic neurolysis, vertebroplasty, kyphoplasty and intrathecal drug delivery. Those procedures have been found to be associated with a decrease in the symptom burden and opioid consumption, improved quality of life, and suggested as having a potentially positive impact on survival. Several studies have recommended using specific interventional techniques at earlier stages, possibly even when opioid treatment is first being considered. Conversely, leaving these options as a last analgesic resource might not be advisable since the burden these procedures might impose on too ill patients is significant. The objective of this review was to collect the available evidence published on the use of interventional treatments for refractory cancer pain with a particular interest in comparing early versus late indications. The results of the search demonstrated a very low number and quality of articles particularly addressing this question. This scarce number of evidence precluded performing a systematic analysis. A detailed and narrative description of the potential benefits of integrating interventional techniques into clinical guidelines at the early stages of the disease is provided.

Measuring direct and indirect tendon parameters to characterize the proximal tendinous complex of the rectus femoris in football and futsal players.

Objective: To present unprecedented radiological parameters that characterize the angle between the direct and indirect tendons of the proximal rectus femoris (RF) and its inclinations and to evaluate the population variability according to demographic variables. Materials and methods: From September 2019 to July 2021, using MRI multiplanar reconstructions of the proximal thigh/hip, two blinded radiologists measured the direct and indirect tendon angle and the inclination of each tendon in different planes. The intra- and inter-observer agreements were assessed with Bland-Altman analysis and intraclass correlation coefficient (ICC). The correlations between radiological parameters and demographic variables were evaluated using linear regression, Student's t-test, and analysis of variance. Results: We performed 112 thigh/hip MRI scans on 91 football players of different age, gender, and disciplines (football and futsal). For observer 1 (the reference), the mean direct and indirect tendon angle was 56.74° ± 9.37, the mean indirect tendon slope was -7.90° ± 7.49, and the mean direct tendon slope was 22.16° ± 5.88. The three measurements showed inter- and intra-observer agreement (mean differences ∼0). No correlation was observed between age and the parameters. Likewise, no statistically significant differences were found for gender, dominant limb, examined limb, and sport. Conclusion: There is an inter- and intra-observer agreement in the measurements of the direct and indirect tendon angle and the inclination of each tendon. There is population variability in the proximal tendinous complex unrelated to demographic factors. These results allow further detection of morphological patterns that represent a risk factor for lesions in the RF in professional football and futsal players and other sports.

Validation of the effectiveness of augmented reality-assisted vascular puncture: An experimental model.

PURPOSE: To demonstrate that the augmented reality-assisted puncture technique improves the efficacy of ultrasound-guided puncture to get central venous access (CVA), allows the image to be obtained without limitations, freeing the hands and keeping the gaze continuously on the working field, which contributes to improving the safety of the procedure. MATERIAL AND METHODS: A gelatin mould with a latex surface and a chicken breast with silicone tubes inside were used to simulate vascular punctures. Images were obtained by an ultrasound scanner and post-processed with a specific software. A hologram was obtained and projected onto the previously delimited surface to be punctured. The variables related to image acquisition, the characteristics of the structure to be cannulated and the percentage of successes in the first attempt were analysed. Six operators were involved, using different ultrasound scanners. Efficiency was examined after the application of technical improvements in the process. RESULTS: Seventy-six punctures were performed, guided by two different ultrasound scanners, divided into two groups: 37 with 33 successes (sigma = 3.52 with a process efficiency of 97.98%) and after technical improvements, 39 with 38 successes (sigma = 4.07 with a process efficiency of 99.4%). There are no significant differences among the operators (X2 p = 0.47) and between the ultrasound scanners (X2 p = 0.56). CONCLUSIONS: The augmented reality ultrasound-assisted CVA technique may be the next step in standardising the process of cannulation of vascular structures. This technique provides greater accuracy, greater comfort by freeing the hands and keeping the gaze on the working field, better ultrasound image quality, and eliminates variability between operators and sonographers.

The Quebec Cannabis Registry: Investigating the Safety and Effectiveness of Medical Cannabis.

Objective: To investigate the safety and effectiveness of medical cannabis (MC) in the real-world clinical practice setting. Design: A 4-year prospective noncomparative registry of adult patients who initiated MC for a variety of indications. This paper reports on patients followed for up to 12 months, with interim visits at 3, 6, and 9 months after enrollment. Setting: Public or private outpatient clinics certified to authorize MC in the province of Quebec, Canada. Participants: Overall, 2991 adult (age ≥18 years) patients (mean age 51 years; 50.2% women) were enrolled between May 2015 and October 2018, with the last follow-up ending in May 2019. Interventions/Exposures: Cannabis products (dried, oil, or other) purchased from a Canadian licensed cannabis producer as authorized by physicians. Main Outcome Measures: The primary outcomes were self-reported pain severity, interference and relief (Brief Pain Inventory [BPI]), symptoms using the Revised Edmonton Symptom Assessment System (ESAS-r) and health-related quality of life dimensions (EQ-5D-5L) at baseline and each follow-up visit. The secondary outcomes were self-reported adverse events (AEs) and characteristics of cannabis treatment. Results: All patient-reported outcomes (BPI, ESAS-r, and EQ-5D-5L) showed a statistically significant improvement at 3 months (all p<0.01), which was maintained or further improved (for pain interference, tiredness, and well-being) over the remainder of the 12-month follow-up. Results also revealed clinically significant improvements in pain interference and tiredness, anxiety, and well-being from baseline. There were 79 AE reports (77 patients), 16 met the regulatory definition of seriousness, in which only 8 AEs were certainly or probably related to MC. Conclusions: MC directed by physicians appears to be safe and effective within 3 months of initiation for a variety of medical indications.

Predictors of Pain Reduction Among Fibromyalgia Patients Using Medical Cannabis: A Long-Term Prospective Cohort Study.

OBJECTIVE: Many patients with fibromyalgia (FM) report using cannabis as a strategy to improve pain. Given that pain often co-occurs with symptoms of anxiety and depression (i.e., negative affect) and sleep problems among patients with FM, improvements in these symptoms might indirectly contribute to reductions in pain intensity following cannabis use. The main objective of the study was to examine whether changes in pain intensity following initiation of medical cannabis among patients with FM could be attributed to concurrent changes (i.e., reductions) in negative affect and sleep problems. METHODS: This was a 12-month prospective cohort study among patients with FM (n = 323) initiating medical cannabis under the care of physicians. Patients were assessed at baseline, and follow-up assessment visits occurred every 3 months after initiation of medical cannabis. Patients' levels of pain intensity, negative affect, and sleep problems were assessed across all visits. RESULTS: Multilevel mediation analyses indicated that reductions in patients' levels of pain intensity were partly explained by concurrent reductions in sleep problems and negative affect (both P < 0.001). This remained significant even when accounting for patients' baseline characteristics or changes in medical cannabis directives over time (all P > 0.05). CONCLUSION: Our findings provide preliminary insight into the potential mechanisms of action underlying pain reductions among patients with FM who are using medical cannabis. Given the high attrition rate (i.e., 75%) observed in the present study at 12 months, our findings cannot be generalized to all patients with FM who are using medical cannabis.

Fluoroscopy-Guided High-Intensity Focused Ultrasound Neurotomy of the Lumbar Zygapophyseal Joints: A Clinical Pilot Study.

OBJECTIVE: To investigate the safety and feasibility of a fluoroscopy-guided, high-intensity focused ultrasound system for zygapophyseal joint denervation as a treatment for chronic low back pain. METHODS: The clinical pilot study was performed on 10 participants diagnosed with lumbar zygapophyseal joint syndrome. Each participant had a documented positive response to a diagnostic block or a previous, clinically beneficial radiofrequency ablation. For a descriptive study, the primary outcome was the safety question. All device- or procedure-related adverse events were collected. Secondary outcome variables included the average numeric rating scale for pain, the Roland-Morris Disability Questionnaire, the Brief Pain Inventory, the Patient Global Impression of Change, the morphine equivalent dose, and the finding of the neurological examination. RESULTS: All participants tolerated the procedure well with no significant device- or procedure-related adverse events; there was one episode of transient pain during the procedure. The average numeric rating scale score for pain decreased from 6.2 at baseline to 2.1 (n = 10) after 1 month, 4.9 (n = 9) after 3 months, 3.0 (n = 8) after 6 months, and 3.0 (n = 6) after 12 months. The ratio of participants who were considered a treatment success was 90% at 1 month, 50% at 3 months, 60% at 6 months, and 40% at 12 months. CONCLUSIONS: The first clinical pilot study using a noninvasive, fluoroscopy-guided, high-intensity focused ultrasound lumbar zygapophyseal neurotomy resulted in no significant device- or procedure-related adverse events and achieved clinical success comparable with that of routine radiofrequency ablation.

The Telemedicine-Based Pediatric Examination of the Neck and Upper Limbs: A Narrative Review.

With the COVID-19 pandemic hastening the adoption of telemedicine into clinical practice, it has also prompted an abundance of new literature highlighting its capabilities and limitations. The purpose of this review is to summarize the current state of the literature on telemedicine applied in the context of a musculoskeletal examination of the neck and upper limbs for children 3 to 18 years old. The PubMed and ScienceDirect databases were searched for relevant articles from January 2015 to August 2021 using a combination of keywords and nested searches. General examination components including inspection, guided self-palpation, range of motion, sensory and motor examination, as well as special testing are described. Although the literature is focused mainly on adult populations, we describe how each component of the exam can be reliably incorporated into a virtual appointment specific to pediatric patients. Caregivers are generally needed for most consultations, but certain maneuvers can be self-performed by older children and adolescents alone. There is general feasibility, validity, and substantial reliability in performing most examination components of the upper limbs remotely, except for the shoulder exam. Compared to those made in person, clinical diagnoses established virtually were found to be either the same or similar in most cases, and management decisions also had high agreement. Despite this, there is evidence that some pediatric providers may not be able to collect all the information needed from a telemedicine visit to make a complete clinical assessment. Lastly, currently available smartphone applications measuring joint range of motion were found to have high reliability and validity. This narrative review not only establishes a foundation for a structured pediatric musculoskeletal examination, but also aims to increase physicians' confidence in incorporating telemedicine into their standard of care.

The Telemedicine-Based Pediatric Examination of the Back and Lower Limbs: A Narrative Review.

The COVID-19 pandemic has accelerated the transition to virtual healthcare while also prompting an abundance of new literature highlighting telemedicine's capabilities and limitations for various medical applications, notably musculoskeletal examinations. Telemedicine provides an opportunity to deliver timely patient- and family-centred care while maintaining physical distancing and improving access to remote communities. This review aims to narrate the current state of the literature on telemedicine applied in the context of a musculoskeletal examination for children aged 3 to 18 years. The PubMed and ScienceDirect databases were searched for relevant articles from January 2015 to August 2021 using a combination of keywords and nested searches. The general examination components relevant to the back and lumbosacral spine, hip, knee, ankle/foot, and gait are described. These components include inspection, palpation, range of motion, motor, and sensory examination as well as special testing. There is general feasibility, validity, and substantial reliability in performing most examination components, and primary diagnoses established virtually were found to be either the same or similar in the vast majority of cases. Despite the current literature focusing mainly on adult populations, we describe how each aspect of the exam can be reliably incorporated into a virtual appointment specific to the pediatric population. Currently available smartphone-based applications that measure joint range of motion were generally found to have high reliability and validity. Caregivers are needed for most of the consultation, especially in younger children, but select physical exam maneuvers can be self-performed by older children and adolescents alone. By providing an overview of the available smartphone tools as well as the reliability and validity of remote assessments, this review not only establishes a foundation for a structured pediatric musculoskeletal examination, but also aims to increase providers' confidence in incorporating telemedicine into their practice.

In Vivo Structure-Function Analysis and Redox Interactomes of Leishmania tarentolae Erv.

Import and oxidative folding of proteins in the mitochondrial intermembrane space differ among eukaryotic lineages. While opisthokonts such as yeast rely on the receptor and oxidoreductase Mia40 in combination with the Mia40:cytochrome c oxidoreductase Erv, kinetoplastid parasites and other Excavata/Discoba lack Mia40 but have a functional Erv homologue. Whether excavate Erv homologues rely on a Mia40 replacement or directly interact with imported protein substrates remains controversial. Here, we used the CRISPR-Cas9 system to generate a set of tagged and untagged homozygous mutants of LTERV from the kinetoplastid model parasite Leishmania tarentolae. Modifications of the shuttle cysteine motif of LtErv were lethal, whereas replacement of clamp residue Cys17 or removal of the kinetoplastida-specific second (KISS) domain had no impact on parasite viability under standard growth conditions. However, removal of the KISS domain rendered parasites sensitive to heat stress and led to the accumulation of homodimeric and mixed LtErv disulfides. We therefore determined and compared the redox interactomes of tagged wild-type LtErv and LtErvΔKISS using stable isotope labeling by amino acids in cell culture (SILAC) and quantitative mass spectrometry. While the Mia40-replacement candidate Mic20 and all but one typical substrate with twin Cx3/9C-motifs were absent in both redox interactomes, we identified a small set of alternative potential interaction partners with putative redox-active cysteine residues. In summary, our study reveals parasite-specific intracellular structure-function relationships and redox interactomes of LtErv with implications for current hypotheses on mitochondrial protein import in nonopisthokonts. IMPORTANCE The discovery of the redox proteins Mia40/CHCHD4 and Erv1/ALR, as well as the elucidation of their relevance for oxidative protein folding in the mitochondrial intermembrane space of yeast and mammals, founded a new research topic in redox biology and mitochondrial protein import. The lack of Mia40/CHCHD4 in protist lineages raises fundamental and controversial questions regarding the conservation and evolution of this essential pathway. Do protist Erv homologues act alone, or do they use the candidate Mic20 or another protein as a Mia40 replacement? Furthermore, we previously showed that Erv homologues in L. tarentolae and the human pathogen L. infantum are not only essential but also differ structurally and mechanistically from yeast and human Erv1/ALR. Here, we analyzed the relevance of such structural differences in vivo and determined the first redox interactomes of a nonopisthokont Erv homologue. Our data challenge recent hypotheses on mitochondrial protein import in nonopisthokonts.

Efficacy and Safety of Nonantibiotic Outpatient Treatment in Mild Acute Diverticulitis (DINAMO-study): A Multicentre, Randomised, Open-label, Noninferiority Trial.

OBJECTIVE: Mild AD can be treated safely and effectively on an outpatient basis without antibiotics. SUMMARY OF BACKGROUND DATA: In recent years, it has shown no benefit of antibiotics in the treatment of uncomplicated AD in hospitalized patients. Also, outpatient treatment of uncomplicated AD has been shown to be safe and effective. METHODS: A Prospective, multicentre, open-label, noninferiority, randomized controlled trial, in 15 hospitals of patients consulting the emergency department with symptoms compatible with AD.The Participants were patients with mild AD diagnosed by Computed Tomography meeting the inclusion criteria were randomly assigned to control arm (ATB-Group): classical treatment (875/125 mg/8 h amoxicillin/clavulanic acid apart from anti-inflammatory and symptomatic treatment) or experimental arm (Non-ATB-Group): experimental treatment (antiinflammatory and symptomatic treatment). Clinical controls were performed at 2, 7, 30, and 90 days.The primary endpoint was hospital admission. Secondary endpoints included number of emergency department revisits, pain control and emergency surgery in the different arms. RESULTS: Four hundred and eighty patients meeting the inclusion criteria were randomly assigned to Non-ATB-Group (n = 242) or ATB-Group (n = 238). Hospitalization rates were: ATB-Group 14/238 (5.8%) and Non-ATB-Group 8/242 (3.3%) [mean difference 2.58%, 95% confidence interval (CI) 6.32 to -1.17], confirming noninferiority margin. Revisits: ATB-Group 16/238 (6.7%) and Non-ATB-Group 17/242 (7%) (mean difference -0.3, 95% CI 4.22 to -4.83). Poor pain control at 2 days follow up: ATB-Group 13/230 (5.7%), Non-ATB-Group 5/221 (2.3%) (mean difference 3.39, 95% CI 6.96 to -0.18). CONCLUSIONS: Nonantibiotic outpatient treatment of mild AD is safe and effective and is not inferior to current standard treatment. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02785549); EU Clinical Trials Register (2016-001596-75).

Telemedicine Applications for the Evaluation of Patients with Non-Acute Headache: A Narrative Review.

The COVID-19 pandemic has spurred a hasty transition to virtual care but also an abundance of new literature highlighting telehealth's capabilities and limitations for various healthcare applications. In this review, we aim to narrate the current state of the literature on telehealth applied to migraine care. First, telemedicine in the context of non-acute headache management has been shown to produce non-inferior patient outcomes when compared to traditional face-to-face appointments. The assignment of patients to telehealth appointments should be made after referring more urgent cases to dedicated in-person clinics. During the virtual appointment, physicians can ask their patients about the "3 F's" in order to perform a thorough assessment of their headaches: frequency of headache days, frequency of acute medication usage and functional impairment. Clinical assessment scores that have been studied and deemed feasible for telemedicine, safe and efficient include the HIT-6, VAS and MIDAS scores. Although MIDAS was found to be redundant and inadequate to use on a daily basis, we suggest that it can be useful in periodic remote follow-up appointments. Additionally, several mobile health apps have been studied including Migraine Buddy, Migraine Coach and Migraine Monitor. All of these are appropriate for use in telemedicine when combined with an adequate trial period with Migraine Buddy being rated the highest, as it captures the most detailed clinical picture. High satisfaction rates have been reported for virtual headache management which were shown to be equal to in-person consults. These are based on patients' perceived increase in convenience due to avoided travel time, less disruption of their daily routine and feeling more comfortable in the environment of their choice. Despite this, limitations such as technological knowledge, access to videoconferencing modalities and having a more impersonal consultation with the physician may hinder some patients from adopting this service.

Day-to-day opioid withdrawal symptoms, psychological distress, and opioid craving in patients with chronic pain prescribed opioid therapy.

BACKGROUND: Research has shown that opioid craving is one of the strongest determinants of opioid misuse in patients with chronic pain. To date, however, little is known on the factors that contribute to opioid craving in these patients. It is possible that patients' physical dependence to opioids, manifested by opioid withdrawal symptoms in between daily opioid doses, contribute to opioid craving. Physical dependence symptoms might also lead to psychological distress, which in turn might contribute to opioid craving. The first objective of this study was to examine the day-to-day association between opioid withdrawal symptoms and opioid craving among patients with chronic pain. We also examined whether negative affect and catastrophic thinking mediated this association. METHODS: In this longitudinal study, chronic pain patients (n = 79) prescribed short-acting opioids completed daily diaries for 14 consecutive days. Diaries assessed a host of pain, psychological, and opioid-related variables. RESULTS: Day-to-day elevations in opioid withdrawal symptoms were associated with heightened opioid craving (p < .001). Results of a multilevel mediation analysis revealed that this association was mediated by patients' daily levels of negative affect and catastrophizing (p < .001). CONCLUSIONS: Our study provides valuable new insights into our understanding of factors that may contribute to prescription opioid craving among patients with chronic pain.

Telehealth and chronic pain management from rapid adaptation to long-term implementation in pain medicine: A narrative review.

The COVID-19 pandemic called for drastic changes to expand and rapidly implement telehealth to prevent breach of care for chronic patients. Responding to the challenge of implementing remote care in chronic pain services, a specialty highly dependent on doctor-patient rapport, physical examination, and frequent follow-up visits requires extensive adaptation involving administrative processes and clinical routines. We present our experience of a successful rapid adaptation to telemedicine paradigm as a response to the COVID-19 pandemic during a time of marked restriction of access to ambulatory hospital services for pediatric and adult chronic pain patients. This narrative review covers current scientific evidence for the use of telehealth for chronic pain management and describes in detail the challenges to implement telemedicine in ambulatory clinics from different perspectives. Best practices for telehealth use are recommended. A proposal for remote physical examination of pain patients is made, based on available evidence in the fields of musculoskeletal medicine and neurology comparing in-person vs remote physical examination. As an internal quality control process, an informal online survey was conducted to assess thoughts and experiences among patients and caregivers using telemedicine consultation services at the pediatric pain clinic. Providing chronic pain management services through telehealth is a viable option for many patients and health care professionals. This is reliant on the availability of appropriate materials and training, with guidelines for both patients and health care workers. With the rapid pace of technological advancements, even further integration of telehealth into routine health care is possible.

Radiation-induced haemorrhagic cystitis after prostate cancer radiotherapy: factors associated to hospitalization and treatment strategies.

BACKGROUND: Late onset of radiation-induced haemorrhagic cystitis (RHC) after radiation therapy (RT) for prostate cancer (PCa) may present or evolve severely, requiring hospitalization with invasive interventions. In the present study, we have analysed the prevalence and risk factors associated with the onset of RHC. METHODS: From January 2002 to May 2017, 1421 patients undertook RT for PCa as a primary, adjuvant, or salvage treatment option. RHC presented in 5.6% (n = 80) of the patients; the diagnosis was based on clinical and endoscopic characteristics. Variables in observation included patients, tumours, and RT-dosimetry characteristics. Patients with a previous history of bladder cancer were excluded. Univariate (Student t/Chi square) and uni-/multivariate Cox regression analysis were performed; the events and time-points were hospitalization and time-to-event, respectively. RESULTS: There were 80 patients with a mean age at RT of 70.1 years (SD 6.4), mean time lag to RHC of 43.9 months (SD 37.5). Median Emergency attendance was two and three times for patients without/with hospitalization, respectively. There were in total 64 admissions with invasive treatment required in 26/36 (72.2%) of the patients hospitalised, including transurethral fulguration in 22 and radical cystectomy in 5. Patients at higher risk of hospitalization were those undertaking antiplatelet/anticoagulant treatment (HR:3.30; CI 95%:1.53-3.30; p = 0.002) and those treated with salvage RT with higher bladder volume receiving >70 Gy (bladder V70) (HR:1.03; CI 95%:1.01-1.05; p = 0.027). At receiving operating characteristic analysis, the cutoff for bladder V70 was 29%. CONCLUSION: Nearly half of patients presenting RHC may require invasive treatment including cystectomy. Risk factors associated with hospitalization are patients undertaking antiplatelet/coagulant treatment and bladder V70 > 29% in salvage RT patients.

Day-to-day hedonic and calming effects of opioids, opioid craving, and opioid misuse among patients with chronic pain prescribed long-term opioid therapy.

ABSTRACT: Concerns have been raised regarding the misuse of opioids among patients with chronic pain. Although a number of factors may contribute to opioid misuse, research has yet to examine if the hedonic and calming effects that can potentially accompany the use of opioids contribute to opioid misuse. The first objective of this study was to examine the degree to which the hedonic and calming effects of opioids contribute to opioid misuse in patients with chronic pain. We also examined whether the hedonic and calming effects of opioids contribute to patients' daily levels of opioid craving, and whether these associations were moderated by patients' daily levels of pain intensity, catastrophizing, negative affect, or positive affect. In this longitudinal diary study, patients (n = 103) prescribed opioid therapy completed daily diaries for 14 consecutive days. Diaries assessed a host of pain, psychological, and opioid-related variables. The hedonic and calming effects of opioids were not significantly associated with any type of opioid misuse behavior. However, greater hedonic and calming effects were associated with heightened reports of opioid craving (both P's < 0.005). Analyses revealed that these associations were moderated by patients' daily levels of pain intensity, catastrophizing, and negative affect (all P's < 0.001). Results from this study provide valuable new insights into our understanding of factors that may contribute to opioid craving among patients with chronic pain who are prescribed long-term opioid therapy. The implications of our findings for the management of patients with chronic pain are discussed.

Neurological toxicity due to antimonial treatment for refractory visceral leishmaniasis.

INTRODUCTION: Although pentavalent antimonials are no longer considered the first-line therapy for visceral leishmaniasis in the developed world, they are still used in certain geographical areas and in refractory cases. These drugs have a great number of adverse effects; however, neurological toxicity has been rarely reported. CASE REPORT: We present a 56-year-old woman who required long-term treatment with antimonial drugs due to refractory visceral leishmaniasis and presented clinically with tremor of extremities, myoclonus, gait disturbances and epileptic seizures. The EEG showed increased beta rhythms and generalized epileptogenic activity. She had a slow but favorable response after the withdrawal of antimonials and the initiation of anticonvulsant therapy. CONCLUSION: Severe but reversible neurological toxicity is a rare adverse effect of prolonged antimonial treatment. More EEG record data are needed to support the suspicion of a possible increase of beta rhythms in this situation.

Consensus-based recommendations for titrating cannabinoids and tapering opioids for chronic pain control.

AIMS: Opioid misuse and overuse have contributed to a widespread overdose crisis and many patients and physicians are considering medical cannabis to support opioid tapering and chronic pain control. Using a five-step modified Delphi process, we aimed to develop consensus-based recommendations on: 1) when and how to safely initiate and titrate cannabinoids in the presence of opioids, 2) when and how to safely taper opioids in the presence of cannabinoids and 3) how to monitor patients and evaluate outcomes when treating with opioids and cannabinoids. RESULTS: In patients with chronic pain taking opioids not reaching treatment goals, there was consensus that cannabinoids may be considered for patients experiencing or displaying opioid-related complications, despite psychological or physical interventions. There was consensus observed to initiate with a cannabidiol (CBD)-predominant oral extract in the daytime and consider adding tetrahydrocannabinol (THC). When adding THC, start with 0.5-3 mg, and increase by 1-2 mg once or twice weekly up to 30-40 mg/day. Initiate opioid tapering when the patient reports a minor/major improvement in function, seeks less as-needed medication to control pain and/or the cannabis dose has been optimised. The opioid tapering schedule may be 5%-10% of the morphine equivalent dose (MED) every 1 to 4 weeks. Clinical success could be defined by an improvement in function/quality of life, a ≥30% reduction in pain intensity, a ≥25% reduction in opioid dose, a reduction in opioid dose to <90 mg MED and/or reduction in opioid-related adverse events. CONCLUSIONS: This five-stage modified Delphi process led to the development of consensus-based recommendations surrounding the safe introduction and titration of cannabinoids in concert with tapering opioids.