Stability of Extemporaneous Oral Tramadol, Fluoxetine, and Doxycycline Suspensions in SyrSpend SF pH4.

Extemporaneous compounding in veterinary practice sometimes represents the only possibility for treating animals in the absence of appropriate commercial formulations, especially for particular species. This method involves manipulating pharmaceutical active ingredients to a suitable dosage and formulation for administration to humans or animals. However, veterinarians and pharmacists should focus on the risk of potential incompatibilities and instability of their preparations. To help practitioners in drug compounding, we investigated the stability of oral suspensions of tramadol, fluoxetine, and doxycycline in a commercial ready-to-use vehicle (SyrSpend). A validated high-performance liquid chromatography method was developed to assay these active pharmaceutical ingredients. The oral suspensions were prepared at two concentration ranges and were stored in amber glass bottles under refrigerated conditions and at room temperature. After 90 days, the average recovery rates were between 90% and 110% for tramadol (5 mg/mL to 30 mg/mL) and doxycycline  (2 mg/mL to 10 mg/mL) without organoleptic modification. For fluoxetine, only the formulation at 2 mg/mL was stable; at higher concentrations, the uniformity of the suspension was compromised.

Management of neuropathic pain induced by surgery: Review of the literature by a group of experts specialized in pain management, anesthesia and surgery.

Chronic postsurgical neuropathic pain (CPSNP) is frequent. While prevalence varies considerably according to type of operation and means of evaluation, it can reach 37% following breast surgery. Identification of risk factors related to the procedure and to the patient and taking into account the development of new, minimally invasive surgical techniques is increasingly nerve-sparing and reduces the likelihood of injury. CPSNP diagnosis in daily practice is facilitated by simple and quickly usable tools such as the NP4 4-question test. Management is based on pharmacological (analgesics, antiepileptics, antidepressants, local anesthetics) and non-pharmacological (kinesitherapy, neurostimulation, psychotherapy) approaches. In light of the present review of the literature, the authors, who constitute an expert group specialized in pain management, anesthesia and surgery, express their support for topical treatments (lidocaine, capsaicin) in treatment of localized postsurgical neuropathic pain in adults.

Fibromyalgia in the workplace: risk factors for sick leave are related to professional context rather than fibromyalgia characteristics- a French national survey of 955 patients.

BACKGROUND: Work and workplace factors are important in fibromyalgia management. We investigated factors associated with sick leave in professionally active women living with fibromyalgia. METHODS: A questionnaire for fibromyalgia patients in employment was developed by pain and occupational physicians and patients' organizations. Women in full-time work, screened for fibromyalgia with the FiRST questionnaire, were recruited for a national online survey. Sick leave over the preceding year was analyzed. RESULTS: In 5 months, we recruited 955 women, with a mean of 37 days of sick leave in the previous year: no sick leave (36%), up to 1 month (38%), 1 to 2 months (14%), more than 2 months (12%). In the groups displayed no differences in demographic characteristics, fibromyalgia symptoms, functional severity and psychological distress were observed. However, they differed in workplace characteristics, commute time, stress and difficulties at work, repetitive work, noisy conditions, career progression problems and lack of recognition, which were strong independent risk factors for longer sick leave. Sedentary positions, an extended sitting position, heavy loads, exposure to thermal disturbances and the use of vibrating tools did not increase the risk of sick leave. CONCLUSIONS: Women with fibromyalgia frequently take sick leave, the risk factors for which are related to the workplace rather than fibromyalgia characteristics. PERSPECTIVE: This is the first study to assess the impact of occupational and clinical factors on sick leave in women living with fibromyalgia. Risk factors were found to be related to the workplace rather than fibromyalgia and personal characteristics. Workplace interventions should be developed for women with fibromyalgia.

Lyme borreliosis and other tick-borne diseases. Guidelines from the French scientific societies (II). Biological diagnosis, treatment, persistent symptoms after documented or suspected Lyme borreliosis.

The serodiagnosis of Lyme borreliosis is based on a two-tier strategy: a screening test using an immunoenzymatic technique (ELISA), followed if positive by a confirmatory test with a western blot technique for its better specificity. Lyme serology has poor sensitivity (30-40%) for erythema migrans and should not be performed. The seroconversion occurs after approximately 6 weeks, with IgG detection (sensitivity and specificity both>90%). Serological follow-up is not recommended as therapeutic success is defined by clinical criteria only. For neuroborreliosis, it is recommended to simultaneously perform ELISA tests in samples of blood and cerebrospinal fluid to test for intrathecal synthesis of Lyme antibodies. Given the continuum between early localized and disseminated borreliosis, and the efficacy of doxycycline for the treatment of neuroborreliosis, doxycycline is preferred as the first-line regimen of erythema migrans (duration, 14 days; alternative: amoxicillin) and neuroborreliosis (duration, 14 days if early, 21 days if late; alternative: ceftriaxone). Treatment of articular manifestations of Lyme borreliosis is based on doxycycline, ceftriaxone, or amoxicillin for 28 days. Patients with persistent symptoms after appropriate treatment of Lyme borreliosis should not be prescribed repeated or prolonged antibacterial treatment. Some patients present with persistent and pleomorphic symptoms after documented or suspected Lyme borreliosis. Another condition is eventually diagnosed in 80% of them.

Lyme borreliosis and other tick-borne diseases. Guidelines from the French Scientific Societies (I): prevention, epidemiology, diagnosis.

Lyme borreliosis is transmitted en France by the tick Ixodes ricinus, endemic in metropolitan France. In the absence of vaccine licensed for use in humans, primary prevention mostly relies on mechanical protection (clothes covering most parts of the body) that may be completed by chemical protection (repulsives). Secondary prevention relies on early detection of ticks after exposure, and mechanical extraction. There is currently no situation in France when prophylactic antibiotics would be recommended. The incidence of Lyme borreliosis in France, estimated through a network of general practitioners (réseau Sentinelles), and nationwide coding system for hospital stays, has not significantly changed between 2009 and 2017, with a mean incidence estimated at 53 cases/100,000 inhabitants/year, leading to 1.3 hospital admission/100,000 inhabitants/year. Other tick-borne diseases are much more seldom in France: tick-borne encephalitis (around 20 cases/year), spotted-fever rickettsiosis (primarily mediterranean spotted fever, around 10 cases/year), tularemia (50-100 cases/year, of which 20% are transmitted by ticks), human granulocytic anaplasmosis (<10 cases/year), and babesiosis (<5 cases/year). The main circumstances of diagnosis for Lyme borreliosis are cutaneous manifestations (primarily erythema migrans, much more rarely borrelial lymphocytoma and atrophic chronic acrodermatitis), neurological (<15% of cases, mostly meningoradiculitis and cranial nerve palsy, especially facial nerve) and rheumatologic (mostly knee monoarthritis, with recurrences). Cardiac and ophtalmologic manifestations are very rarely encountered.

Comorbid fibromyalgia: A qualitative review of prevalence and importance.

Fibromyalgia (FM) may be an unrecognized cause of suffering for persons with an array of medical conditions. This is especially true for illness that is characterized by pain of any nature. Once believed to be a unique diagnosis, FM is recently reported to occur concomitantly with various rheumatic diseases, and importantly adversely impacts global health status. However, there is increasing report of FM associated with other diseases that are not defined by chronic pain. This qualitative review examines the evidence for comorbid FM in illness, and where available the effect of FM on the primary disease. Other than for musculoskeletal disorders, the published literature reporting an association of FM with illness is limited with scanty reports for some neurological, gastrointestinal, mental health and other overlapping pain conditions. Comorbid FM adversely affects both health status and outcome for rheumatic diseases, but with limited study in other diseases. When unrecognized, comorbid FM may be mistaken as poor control of the primary disease, leading to incorrect treatment decisions. FM may be a neglected condition that pervades many conditions and may contribute to the burden of illness. Physicians should be alert to the possibility of comorbid FM, and symptoms of FM should be specifically addressed. SIGNIFICANCE: Comorbid fibromyalgia (FM) in other medical conditions is largely unrecognized. When reported as accompanying rheumatic diseases, FM adversely affects global health status. With limited reports of comorbid FM with other conditions, neglect to diagnose comorbid FM may misdirect treatments.

Assessment and manifestation of central sensitisation across different chronic pain conditions.

Different neuroplastic processes can occur along the nociceptive pathways and may be important in the transition from acute to chronic pain and for diagnosis and development of optimal management strategies. The neuroplastic processes may result in gain (sensitisation) or loss (desensitisation) of function in relation to the incoming nociceptive signals. Such processes play important roles in chronic pain, and although the clinical manifestations differ across condition processes, they share some common mechanistic features. The fundamental understanding and quantitative assessment of particularly some of the central sensitisation mechanisms can be translated from preclinical studies into the clinic. The clinical perspectives are implementation of such novel information into diagnostics, mechanistic phenotyping, prevention, personalised treatment, and drug development. The aims of this paper are to introduce and discuss (1) some common fundamental central pain mechanisms, (2) how they may translate into the clinical signs and symptoms across different chronic pain conditions, (3) how to evaluate gain and loss of function using quantitative pain assessment tools, and (4) the implications for optimising prevention and management of pain. The chronic pain conditions selected for the paper are neuropathic pain in general, musculoskeletal pain (chronic low back pain and osteoarthritic pain in particular), and visceral pain (irritable bowel syndrome in particular). The translational mechanisms addressed are local and widespread sensitisation, central summation, and descending pain modulation. SIGNIFICANCE: Central sensitisation is an important manifestation involved in many different chronic pain conditions. Central sensitisation can be different to assess and evaluate as the manifestations vary from pain condition to pain condition. Understanding central sensitisation may promote better profiling and diagnosis of pain patients and development of new regimes for mechanism based therapy. Some of the mechanisms underlying central sensitisation can be translated from animals to humans providing new options in development of therapies and profiling drugs under development.

[Misuse and dependence on prescription opioids: Prevention, identification and treatment]. / Mésusage et dépendance aux opioïdes de prescription : prévention, repérage et prise en charge.

Since the 1990s, the use of prescription opioids has largely spread, which has brought a real progress in the treatment of pain. The long-term use of prescription opioid is sometimes required, and may lead to pharmacological tolerance and withdrawal symptoms, i.e. pharmacological dependence on prescription opioids. Occasionally, this may also lead to misuse of prescription opioids (MPO). MPO preferentially occurs in vulnerable individuals, i.e., those with a young age, history of other addictive or psychiatric disorders, especially anxious and depressive disorders. MPO is associated with numerous complications, including an increased risk of fatal overdose. Prevention of MPO begins before the opioid prescription, with the identification of potential vulnerability factors. A planned and personalized monitoring should be systematically implemented. In vulnerable patients, contractualizing the prescription is warranted. During follow-up, the relevance of the prescription should be regularly reconsidered, according to the benefit observed on pain and the potential underlying signs of MPO. Patients with suspected MPO should be referred early to pain or addiction centers. The treatment of MPO should be based on multidisciplinary strategies, involving both the addiction and pain aspects: progressive opioid withdrawal, non-pharmacological measures against pain, or switching to medication-assisted treatment of addiction (i.e., buprenorphine or methadone).

Pain patients' letters: The visit before the visit - A qualitative analysis of letters from patients referred to a tertiary pain center.

BACKGROUND: Pain centers manage only selected patients, and have long waiting lists. Some patients spontaneously send letters, before the visit, and these letters represent the first contact between the patients and the pain centers. We report a study of the content and format of these letters, for a patient perspective analysis. METHODS: During a 3 month-period, all newly referred patients to a tertiary pain center were considered. If a patient letter was provided, it was collected for analysis. Qualitative analyses including semantic and content analyses were performed to identify themes and categories. RESULTS: Among 138 newly referred patients, 44 had sent a letter before consultation. Content analysis of 42 letters disclosed four themes: I) pain experience; II) impact of the pain problem; III) patient history; and IV) expectations. These themes could be distributed along four pain dimensions: (1) physical; (2) psycho-affective; (3) social; and (4) temporal. This first study on patient letters reveals that a bio-psychosocial model. Patients contribute actively to their trajectory, not only as healthcare seekers but also by constructing their narrative identity. CONCLUSIONS: Patient letters constitute narrative material to be integrated into clinical analysis, alongside patient interviews, especially in pain management. Pain specialists should take account of this narrative approach to better understand the unvoiced and sometimes silent experience of pain. This may increase quality of medical care by including patient-centered data in an original method. Further studies may be valuable to analyze the possible contributions of such letters to patient management. SIGNIFICANCE: Patients' letters constitute original narrative material to be integrated into clinical analysis, especially for pain management. Patients' letters analyses may improve the patient physician relationship, by understanding patient's perspectives, beliefs and expectations.

EULAR revised recommendations for the management of fibromyalgia.

OBJECTIVE: The original European League Against Rheumatism recommendations for managing fibromyalgia assessed evidence up to 2005. The paucity of studies meant that most recommendations were 'expert opinion'. METHODS: A multidisciplinary group from 12 countries assessed evidence with a focus on systematic reviews and meta-analyses concerned with pharmacological/non-pharmacological management for fibromyalgia. A review, in May 2015, identified eligible publications and key outcomes assessed were pain, fatigue, sleep and daily functioning. The Grading of Recommendations Assessment, Development and Evaluation system was used for making recommendations. RESULTS: 2979 titles were identified: from these 275 full papers were selected for review and 107 reviews (and/or meta-analyses) evaluated as eligible. Based on meta-analyses, the only 'strong for' therapy-based recommendation in the guidelines was exercise. Based on expert opinion, a graduated approach, the following four main stages are suggested underpinned by shared decision-making with patients. Initial management should involve patient education and focus on non-pharmacological therapies. In case of non-response, further therapies (all of which were evaluated as 'weak for' based on meta-analyses) should be tailored to the specific needs of the individual and may involve psychological therapies (for mood disorders and unhelpful coping strategies), pharmacotherapy (for severe pain or sleep disturbance) and/or a multimodal rehabilitation programme (for severe disability). CONCLUSIONS: These recommendations are underpinned by high-quality reviews and meta-analyses. The size of effect for most treatments is relatively modest. We propose research priorities clarifying who will benefit from specific interventions, their effect in combination and organisation of healthcare systems to optimise outcome.

Acute pain Factors predictive of post-operative pain and opioid requirement in multimodal analgesia following knee replacement.

BACKGROUND: Despite the development of multimodal analgesia for postoperative pain management, opioids are still required for effective pain relief after knee arthroplasty. We aimed to identify the determinants of post-operative pain intensity and post-operative opioid requirement in this context. METHODS: In this observational prospective study, we recorded patient characteristics, pre-operative pain intensity, anxiety and depression levels, sensitivity and pain thresholds in response to an electrical stimulus, and mu-opioid receptor (OPRM1) and catechol-O-methyltransferase (COMT) single-nucleotide polymorphisms. Multivariate linear regression models were used to identify predictors of post-operative pain at rest and opioid requirement. RESULTS: We included 109 patients. Pre-operative pain at rest (p = 0.047), anxiety level (p = 0.001) and neuropathic pain symptoms (p = 0.030) were independently and positively associated with mean post-operative pain intensity adjusted for mean post-operative morphine equivalent dose (MED). Mean post-operative pain intensity at rest was lower (p = 0.006) in patients receiving celecoxib and pregabalin in the post-operative period, with all other variables constant. Mean post-operative MED over 5 days was low, but highly variable (78.2 ± 32.1 mg, from 9.9 to 170 mg). Following adjustment for mean post-operative pain intensity, it was independently negatively correlated with age (p = 0.004), and positively correlated with associated paracetamol treatment (p = 0.031). No genetic effect was detected in our sample. CONCLUSIONS: Our findings suggest that clinicians could use the pre-operative pain profile, in terms of anxiety levels, neuropathic pain symptoms, and chronic pre-operative pain intensity, to improve the efficacy of pain management after knee surgery.

Are there different predictors of analgesic response between antidepressants and anticonvulsants in painful diabetic neuropathy?

BACKGROUND: To investigate baseline demographics and disease characteristics as predictors of the analgesic effect of duloxetine and pregabalin on diabetic peripheral neuropathic pain (DPNP). METHODS: Based on data from the COMBO-DN study, a multinational clinical trial in DPNP, the potential impact of baseline characteristics on pain relief after 8-week monotherapy with 60 mg/day duloxetine or 300 mg/day pregabalin was assessed using analyses of covariance. Subgroups of interest were characterized regarding their baseline characteristics and efficacy outcomes. RESULTS: A total of 804 patients were evaluated at baseline. A significant interaction with treatment was observed in the mood symptom subgroups with a larger pain reduction in duloxetine-treated patients having no mood symptoms [Hospital Anxiety and Depression Scale (HADS) depression or anxiety subscale score <11; -2.33 (duloxetine); -1.52 (pregabalin); p = 0.024]. There were no significant interactions between treatment for subgroups by age (<65 or ≥65 years), gender, baseline pain severity [Brief Pain Inventory Modified Short Form (BPI-MSF) average pain <6 or ≥6], diabetic neuropathy duration (≤2 or >2 years), baseline haemoglobin A1c (HbA1c) (<8% or ≥8%), presence of comorbidities and concomitant medication use. CONCLUSIONS: Our analyses suggest that the efficacy of duloxetine and pregabalin for initial 8-week treatment in DPNP was consistent across examined subgroups based on demographics and disease characteristics at baseline except for the presence of mood symptoms. Duloxetine treatment appeared to be particularly beneficial in DPNP patients having no mood symptoms.

Chronic endocarditis due to Legionella anisa: a first case difficult to diagnose.

Endocarditis due to Legionella spp. is uncommon but presumably underestimated given the prevalence of Legionellae in the environment. We report a first and unusual case of chronic native valve endocarditis due to L. anisa and advocate that the diagnosis of endocarditis be made collaboratively between the cardiologist, surgeon, microbiologist and pathologist.

Efficacy of a 2% climbazole shampoo for reducing Malassezia population sizes on the skin of naturally infected dogs.

OBJECTIVE OF THE STUDY: Shampoo therapy is often recommended for the control of Malassezia overgrowth in dogs. The aim of this study was to evaluate the in vivo activity of a 2% climbazole shampoo against Malassezia pachydermatis yeasts in naturally infected dogs. ANIMALS: Eleven research colony Beagles were used. MATERIALS AND METHODS: The dogs were distributed randomly into two groups: group A (n=6) and group B (n=5). Group A dogs were washed with a 2% climbazole shampoo, while group B dogs were treated with a physiological shampoo base. The shampoos were applied once weekly for two weeks. The population size of Malassezia yeasts on skin was determined by fungal culture through modified Dixon's medium contact plates pressed on left concave pinna, axillae, groins, perianal area before and after shampoo application. Samples collected were compared by Wilcoxon rank sum test. RESULTS: Samples collected after 2% climbazole shampoo application showed a significant and rapid reduction of Malassezia population sizes. One hour after the first climbazole shampoo application, Malassezia reduction was already statistically significant and 15 days after the second climbazole shampoo, Malassezia population sizes were still significantly decreased. No significant reduction of Malassezia population sizes was observed in group B dogs. CONCLUSION: The application of a 2% climbazole shampoo significantly reduced Malassezia population sizes on the skin of naturally infected dogs. Application of 2% climbazole shampoo may be useful for the control of Malassezia overgrowth and it may be also proposed as prevention when recurrences are frequent.

More ubiquitous effects from non-pharmacologic than from pharmacologic treatments for fibromyalgia syndrome: a meta-analysis examining six core symptoms.

This study aimed to characterize and compare the efficacy profile on six fibromyalgia syndrome (FM) core symptoms associated with pharmacologic and non-pharmacologic treatments. We screened PubMed, Embase and the Cochrane Library for FM articles from 1990 to September 2012 to analyse randomized controlled trials comparing pharmacologic or non-pharmacologic treatments to placebo or sham. Papers including assessments of at least 2 of the 6 main FM symptom domains - pain, sleep disturbance, fatigue, affective symptoms (depression/anxiety), functional deficit and cognitive impairment - were selected for analysis. Studies exploring pharmacologic approaches (n = 21) were mainly dedicated to treating a small number of dimensions, mostly pain. They were of good quality but were not prospectively designed to simultaneously document efficacy for the management of multiple core FM symptom domains. Only amitriptyline demonstrated a significant effect on as many as three core FM symptoms, but it exhibited many adverse effects and was subject to early tachyphylaxis. Studies involving non-pharmacologic approaches (n = 64) were typically of poorer quality but were more often dedicated to multidimensional targets. Pool therapy demonstrated significant effects on five symptom domains, repetitive transcranial magnetic stimulation on four domains, balneotherapy on three domains and exercise, cognitive behaviour therapy and massage on two domains each. Differences between pharmacologic and non-pharmacologic approaches may be related to different modes of action, tolerability profiles and study designs. Very few drugs in well-designed clinical trials have demonstrated significant relief for multiple FM symptom domains, whereas non-pharmacologic treatments with weaker study designs have demonstrated multidimensional effects. Future therapeutic trials for FM should prospectively examine each of the core domains and should attempt to combine pharmacologic and non-pharmacologic therapies in well-designed clinical trials.

Association between passive smoking and atopic dermatitis in dogs.

Onset of atopic dermatitis and occurrence of related skin lesions are influenced by various environmental factors in humans, and companion animals. Several studies have demonstrated an association between passive smoking and the development of atopic dermatitis in children. This association has never been investigated in the dog to our knowledge. We enrolled 161 dogs seen at dermatology and vaccination consultations over a six-month period for this study. Dog owners were asked to complete a questionnaire, to evaluate the exposure of the dog to tobacco smoke. The atopic or non-atopic status of the dog was assessed on the basis of Favrot's criteria (history, clinical examination and cutaneous cytology for Malassezia). Analysis of the data for the 161 dogs enrolled revealed a significant association between high levels of passive exposure to tobacco smoke (cigarette consumption divided by the area of the home) and the presence of atopic dermatitis in the dogs (OR, 4.38; 95% CI, 1.10-17.44; p=0.03; NNH (number needed to harm) 3, 95% CI 2-52). The prevalence of atopic dermatitis showed a slight, but non-significant association with breed predisposition. Dogs with high levels of exposure to tobacco smoke may have a higher risk of atopic dermatitis than non-exposed dogs.

Prevalence and impact of constipation and bowel dysfunction induced by strong opioids: a cross-sectional survey of 520 patients with cancer pain: DYONISOS study.

OBJECTIVE: To describe the prevalence of opioid-induced constipation (OIC) in patients with cancer pain according to the Knowles-Eccersley-Scott symptom score (KESS), the different symptoms of opioid-induced bowel dysfunction (OIBD), and to assess the impact of OIBD on patient's quality-of-life. METHODS: A cross-sectional observational study, using the KESS questionnaire and the physician's subjective assessment of constipation, and other questionnaires and questions on constipation, OIBD, and quality-of-life, carried out on 1 day at oncology day centres and hospitals. RESULTS: Five hundred and twenty patients were enrolled at 77 centres in France; 61.7% of patients (n = 321) showed a degree of constipation that is problematic for the patient according to KESS (between 9-39). Even more patients, 85.7% (n = 438), were considered constipated according to the physician's subjective assessment-despite laxative use (84.7% of patients). Quality-of-life was significantly reduced in constipated vs non-constipated patients for both PAC-QoL (p < 0.0001 for total score and each dimension) and the SF-12 questionnaires (statistically significant for all dimensions except physical state and role physical). OIC and OIBD led to hospitalization (16% of patients), pain (75% of patients), and frequent changes in opioid and laxative treatment. KEY LIMITATIONS: This cross-sectional study, in a selected population of cancer patients, has measured prevalence and impact of OIBD. Further confirmation could be sought through the use of longitudinal studies, and larger populations, such as non-cancer pain patients treated with opioids. CONCLUSIONS: Cancer patients taking opioids for pain are very frequently constipated, even if they are prescribed laxatives. This leads to relevant impairments of quality-of-life.