Perceived treatment satisfaction in patients with systemic rheumatic diseases treated with biologic therapies: results of a self-reported survey.

Biological agents are widely used for the management of systemic rheumatic diseases (SRDs) and their therapeutic implications have been expanded beyond inflammatory arthropathies to more complicated autoimmune disorders, such as systemic lupus erythematosus, vasculitis, and systemic sclerosis. The aim of this study was to investigate treatment satisfaction and overall experience of SRDs' patients receiving biologics as well as to explore patient's perspectives on the quality of services provided by rheumatology departments and to determine factors related to the level of satisfaction. We performed a synchronous correlation study. Patients with SRDs answered an anonymous questionnaire assessing their satisfaction and how treatment with biologics has affected their quality of life and functionality. Sample consisted by 244 patients (65.2% women), with mean age of 50.4 years, and the most common diagnosis was rheumatoid arthritis (37.3%). Sixty one percent of patients received intravenous therapy and 39% subcutaneously. Overall, 80.5% of the patients reported a positive/very positive effect of their treatment on their life. The average total patient satisfaction from the unit was 79.8%. The presence of mental disease was significantly associated with less positive impact of the treatment on patients' life, worse quality of life, and greater pain. In conclusion, patients with a broad spectrum of SRDs were generally satisfied and treatment with biologic regimens appeared to have a positive impact on several aspects of their life. The majority of patients were at least satisfied with all the characteristics of the unit staff and better quality of life was associated with greater satisfaction about the Unit and more positive affect of the treatment in patients' life.

The inhibitory effect of tocilizumab on systemic bone loss and tendon inflammation in a juvenile Collagen-Induced arthritis rat model.

PURPOSE OF THE STUDY: Reduced Bone Mineral Density (BMD) is a prevalent comorbidity in Juvenile Idiopathic Arthritis (JIA). Enthesitis and other tendon abnormalities, such as tenosynovitis, tendinitis and tendon ruptures are, also, common extra-articular manifestations of the disease. The aim of the present study was to investigate the effect of tocilizumab, an antibody that binds the Interleukin-6 (IL-6) Receptor, on inflammation-related bone loss and tendon inflammation in an animal model of JIA. MATERIALS AND METHODS: The Collagen-Induced Arthritis (CIA) model was induced in male rats followed by intraperitoneal administration of tocilizumab for 8 weeks. Methotrexate, the most widely used Disease-Modifying Antirheumatic Drug in the management of JIA, was, also, administered, either as a monotherapy or as an add-on therapy to tocilizumab. BMD was evaluated with Micro-Computed Tomography (Micro-CT) and histopathological examination. Tendon damage was, also, assessed histologically. Finally, two pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNF-a) and Interleukin-23 (IL-23) were quantified in tendon tissues by ELISA analysis. RESULTS: Tocilizumab-treated animals exhibited a significantly improved trabecular microarchitecture on micro-CT analysis and histological examination. Tendon morphology was also improved. Anti-IL-6 treatment led to a significant decrease in TNF-a and IL-23 expression in tendon tissue. CONCLUSIONS: The results of the present study provide evidence that tocilizumab reduces inflammation-related bone loss and suppresses tendon inflammation in a juvenile CIA rat model. These findings offer perspectives for the management of osteoporosis and enthesitis in JIA.

Efficacy and safety of anti-sclerostin antibodies in the treatment of osteoporosis: A meta-analysis and systematic review.

Osteoporosis is a chronic disease with an increasing prevalence. Anti-sclerostin antibodies are being investigated for the treatment of osteoporosis. The aim of this systematic review and meta-analysis is to evaluate the efficacy and safety of antis-sclerostin antibodies compared to placebo and conventional therapies (alendronate and teriparatide) in the treatment of osteoporosis. Randomized controlled trials were searched from PubMed, EMBASE and Cochrane Central Register of Controlled Trails (CENTRAL) from their inception up to June 2021 by using Medical Subject Headings terms "anti-sclerostin antibody", "romosozumab", "blosozumab", "AMG 785″, "LY2541546", and "osteoporosis". Two investigators independently screened eligible studies, assessed the risk of bias and extracted the data from each study. The I2 index was used to assess heterogeneity. Meta-analysis was conducted using the Review Manager Software (RevMan, Version 5.4). The GRADE approach was used to rate the quality of evidence for all the pooled outcomes. 8 RCTs with 12,416 patients met the inclusion criteria. Anti-sclerostin antibodies significantly increased lumbar spine, total hip and femoral neck bone mineral density compared to placebo, alendronate and teriparatide at both 6 and 12 mo. Adverse events were comparable between anti-sclerostin antibodies and other treatments, except for the incidence of injection-site reactions that was higher in the anti-sclerostin antibody groups. Anti-sclerostin antibodies represent a valid theurapeutic option in the treatment of osteoporosis. Further studies with longer duration and follow-up are needed to confirm the results of this meta-analysis.

Total Annual Economic Burden of Patients with Sickle Cell Disease in Steady State in Greece.

Sickle cell disease includes a group of congenital hemolytic anemias, all characterized by the predominance of Hb S (HBB: c.20A>T). The population movement due to economic migration or escape from conflict zones will further affect the health systems of countries by either increasing the number of patients or forcing countries to create care units for sickle cell disease patients. This will probably also increase the incidence of the disease in areas where their incidence and prevalence were previously low. In the present study, an attempt has been made to estimate the total annual cost of the treatment of sickle cell disease in Greece. This was the first attempt to calculate the total annual cost of treating sickle cell disease patients in a steady state. The annual cost of sickle cell disease was estimated to be €21,152,340.00 (US$25,219,300.41), without calculating the cost of hospitalization for severe complications. Since 2013, in Greece, a pharmaceutical expenditure limit (decreasing with the years) has been budgeted at €1,945,000,000.00 (US$2,318,965,150.00), annually. It is therefore calculated that approximately 1.0% of the budget allocated to pharmaceutical spending is used to treat patients with sickle cell disease.

Infliximab prevents systemic bone loss and suppresses tendon inflammation in a collagen-induced arthritis rat model.

Reduced Bone Mineral Density (BMD) and tendon abnormalities, such as tenosynovitis and enthesitis, are prevalent comorbidities in patients with rheumatoid arthritis (RA). The aim of the present study was to investigate the effect of chronic treatment with infliximab on BMD and tendon inflammation in an animal model of inflammatory arthritis. Collagen-Induced Arthritis (CIA) was induced in rats, followed by long-term intraperitoneal administration of infliximab. Two additional groups of animals received methotrexate either as a monotherapy or as a co-treatment to infliximab. BMD was evaluated by Micro-Computed Tomography (Micro-CT) and bone histological examination. Tendon inflammation was assessed histologically and by quantitative ELISA analysis of pro-inflammatory cytokines in tendon tissues. Both methotrexate and infliximab treatment alleviated joint inflammation and reduced paw edema. Infliximab-treated animals exhibited an improved trabecular microarchitecture on micro-CT and histological analysis compared to both non-treated and methotrexate-treated animals. Infliximab almost reversed the pathological changes in tendons induced by CIA. Finally, we observed statistically significant declines in tendon TNF-a and IL-23 levels after infliximab treatment. Our study provides evidence that infliximab prevents arthritis-related osteoporosis and suppresses tendon inflammation in an animal model of inflammatory arthritis, in addition to controlling disease activity. These findings offer perspectives for the management of osteoporosis and enthesitis in RA.

The Use of Collagen-Induced Arthritis Animal Model on Studying Bone Metabolism.

CIA is a well-studied animal model of autoimmune arthritis. It resembles rheumatoid arthritis as far as histopathological changes and molecular pathogenesis are concerned. CIA is induced by immunization with collagen type II in susceptible strains. The purpose of this review is to assess the use of CIA animal model on bone metabolism and the potential therapeutic agents that could reverse this effect. A database search from their inception to 2019 was conducted to identify experimental animal studies pertinent to CIA model and bone examination. Studies including ovariectomy or without a direct comparison between control and CIA groups were excluded. Forty-eight articles were considered suitable for inclusion. Imaging techniques, biomechanical analysis, histopathological studies, and molecular biology techniques were employed. A decrease in bone mineral density in CII arthritic animals was established. Bone loss was either periarticular, generalized or both. Although trabecular bone loss was clear, the effect on cortical bone is yet to be determined. The proposed mechanism is an imbalance between bone formation and resorption as a result of osteoclast activation. The signal pathways implicated appear to be the RANKL/RANK/OPG and the Wnt pathway. Many therapeutic targets were investigated with promising results.

Levetiracetam as preventive treatment in adults with migraine: an up-to-date systematic review and quantitative meta-analysis.

PURPOSE: The aim of this systematic review was to evaluate current evidence on the efficacy and safety of levetiracetam as migraine prophylaxis in adult patients suffering from migraine attacks. METHODS: PubMed, Scopus, Cochrane Central Register of Controlled Trials, and International Web of Science were searched (last search in August 2018) for studies investigating levetiracetam for migraine prophylaxis in adults. Both randomized and non-randomized trials were eligible. Efficacy was the primary outcome, but tolerability was also investigated. The study is registered on PROSPERO, number CRD42018088900. RESULTS: Nine studies, enrolling 215 patients, were included. Levetiracetam decreased the frequency of attacks with headache in all studies, with a pooled mean difference of -3.02 (95% CI: -4.59 to -1.45; I2 = 0%), -4.65(-7 to -2.3; I2 = 0%), and -5.71 (-8.60 to -2.82; I2 = 0%) at 1, 3, and 6 months compared with baseline. Three randomized controlled trials were included, and levetiracetam was superior to placebo in two but was inferior to sodium valproate in reducing headache frequency. Similar results were found in the other indices of efficacy, and levetiracetam was generally well tolerated. CONCLUSION: Levetiracetam may be a relatively safe and efficacious treatment for the prophylaxis of migraine based on limited evidence, most from uncontrolled studies. Further evidence from randomized controlled trials is necessary.

Predictors of influenza vaccination among elderly: a cross-sectional survey in Greece.

BACKGROUND: Senior individuals are particularly vulnerable to influenza. Research suggests that protection against the virus and its transmission in this high-risk group of the population can be achieved by active immunization against the pathogen. AIMS: To explore and analyze the attitudes, knowledge and behavior of people over the age of 60 on influenza vaccination. POPULATION AND METHODS: This cross-sectional survey included people over the age of 60 who were eligible candidates for the influenza vaccine from 3 regions from Northern and 1 region from Southern Greece. A self-completed questionnaire based upon the Theory of Planned Behaviour, the Motivation for Vaccination (MoVac-flu) and the Vaccination Advocacy Scale (MovAd) was administered to the participants. Demographic characteristics and information about health status were also obtained. RESULTS: The final sample included 318 participants with mean age of 70.7 years. More than half of the participants (56.6%) had received a flu vaccine in 2018 while 50.8% received it annually in previous years. Behavioral (p < 0.001), normative (p < 0.001), and control beliefs (p < 0.001), promoted the uptake of the vaccine and the increased intention score (p < 0.001) was associated with increased probability of vaccination. Greater age (p = 0.001) and frequent visits to the doctors (p = 0.003) had a positive influence upon the uptake of the vaccine. CONCLUSIONS: Only a small proportion of those over the age of 60 had received the influenza vaccine. This finding is worrying, as it indicates the impact that a future outbreak of seasonal influenza could exert upon vulnerable groups. There is an urgent need for further, better and more evidence-based information from healthcare professionals to achieve greater vaccination coverage in the community.

Analgesic Efficacy and Safety of Local Infiltration of Tramadol in Pediatric Tonsillectomy Pain: A Systematic Review and Meta-Analysis.

OBJECTIVES: The aim of this systematic review and meta-analysis was to appraise clinical evidence of the impact of peritonsillar infiltration of tramadol, on postoperative pain control and the occurrence of adverse effects in children undergoing tonsillectomy. METHODS: A database search was conducted to identify randomized controlled trials (RCTs) pertinent to peritonsillar infiltration of tramadol compared to no treatment (placebo) or other analgesic regimens. The outcomes of interest were postoperative pain intensity, time to first analgesic demand, rescue analgesic consumption up to 24 hours after intervention, and the occurrence of adverse events. RESULTS: Twelve RCTs enrolling 972 pediatric patients were selected for qualitative analysis, among which eight were suitable for meta-analysis. Tramadol infiltration induced a significant reduction of pain intensity up to 24 hours post-tonsillectomy (mean difference [MD], -2.31; 95% confidence interval [CI], -3.49 to -1.12; P < 0.001; I2  = 97%) and time to first analgesic (MD 180.54; 95% CI, 56.91 to 304.18; P = 0.004; I2  = 99%), with no profound impact on postoperative nausea and vomiting (risk ratio [RR] 0.98; 95% CI, 0.73 to 1.32; P = 0.90; I2  = 0%) compared to the placebo group. The analgesic efficacy of tramadol infiltration was equivalent to the local or systematic use of ketamine or infiltration with local anesthetics. This effect was further enhanced when tramadol infiltration served as an adjunct to other analgesic interventions. No serious adverse events were reported. CONCLUSIONS: In children undergoing tonsillectomy, peritonsillar infiltration of tramadol is associated with a postoperative analgesic benefit when compared to placebo, with negligible adverse events. Yet, no definite conclusion can be drawn due to the low quality, considerable heterogeneity, and paucity of the available data.

Nonmedical Use of Prescription Medications Among Medical Students in Greece: Prevalence of and Motivation for Use.

BACKGROUND: Non-medical use of prescription medications has risen to unprecedented levels over the past decade worldwide; however, studies assessing misuse across medical students are sparse. OBJECTIVES: The purpose of this study was to1) estimate the lifetime and the past-year prevalence of non-medical use of prescription medications among medical students in Greece 2) identify the motivation for use. METHODS: 591 medical students completed an anonymous, self-administered, web-based survey assessing lifetime and past-year prevalence of non-medical use of four classes of prescription drugs (opioid painkillers, tranquillizers, sleeping and stimulant medications). According to the motivation to use the responders were classified into three subtypes (selftreatment, recreational, and mixed). RESULTS: The prevalence of lifetime use was 10.7% for at least one of the four prescription drug classes and 9% of the respondents reported lifetime misuse of multiple categories of prescription drugs. The past-year prevalence was approximately 7.7% for at least one of the four prescription drug classes, while the majority misused the drugs "1-2 times per year". Senior students used tranquilizers more than junior students. Self-treatment and mixed subtypes of tranquillizers misuse was more prevalent among women than men while the self-treatment subtype was the most prevalent subtype in all the four drug classes. CONCLUSIONS: This is the first study investigating non-medical use of prescription medications among Greek medical students and indicates a high prevalence of misuse of some categories of prescription drugs, mostly for self-treatment purposes.

Efficacy and safety of prophylactic levetiracetam in supratentorial brain tumour surgery: a systematic review and meta-analysis.

AIMS: The aim of this study was to perform an up-to-date systematic review and meta-analysis on the efficacy and safety of prophylactic administration of levetiracetam in brain tumour patients. METHOD: A systematic review of studies published until April 2015 was conducted using Scopus/Elsevier, EMBASE and MEDLINE. The search was limited to articles reporting results from adult patients, suffering from brain tumour, undergoing supratentorial craniotomy for tumour resection or biopsy and administered levetiracetam in the perioperative period for seizure prophylaxis. Outcomes included the efficacy and safety of levetiracetam, as well as the tolerability of the specific regimen, defined by the discontinuation of the treatment due to side effects. RESULTS: The systematic review included 1148 patients from 12 studies comparing levetiracetam with no treatment, phenytoin and valproate, while only 243 patients from three studies, comparing levetiracetam vs phenytoin efficacy and safety, were included in the meta-analysis. The combined results from the meta-analysis showed that levetiracetam administration was followed by significantly fewer seizures than treatment with phenytoin (OR = 0.12 [0.03-0.42]: χ(2) = 1.76: I(2) = 0%). Analysis also showed significantly fewer side effects in patients receiving levetiracetam, compared to other groups (P < 0.05). The combined results showed fewer side effects in the levetiracetam group compared to the phenytoin group (OR = 0.65 [0.14-2.99]: χ(2) = 8.79: I(2) = 77%). CONCLUSIONS: The efficacy of prophylaxis with levetiracetam seems to be superior to that with phenytoin and valproate administration. Moreover, levetiracetam use demonstrates fewer side effects in brain tumour patients. Nevertheless, high risk of bias and moderate methodological quality must be taken into account when considering these results.

Memantine's action against aminoglycoside-induced ototoxicity.

The objectives of this study were (1) to assess the protective role of NMDA antagonists against the ototoxic effects of aminoglycosides, (2) to provide any possible evidence between ototoxicity due to aminoglycosides and excitotoxicity. An animal experiment was conducted. Twenty-eight, 3-month-old female New Zealand rabbits, weighing 1,000-1,500 g, were studied prospectively for 28 days after intramuscular administration of amikacin (15 mg/kg/day divided into two equal doses) for 14 days. Twenty-one rabbits were categorized into three equal treatment groups and seven animals received no medication and served as the control group. The animals of A, B and C groups were injected, intramuscularly, with amikacin 15 mg/kg/day, divided into two equal doses every day for 14 days. Animals of group A received in parallel memantine (per os) and those of group B received p.o. the same volume of placebo solution. The rabbits of the third group (group C) received on the 15th day and every 2 days for the next 2 weeks, until the day 28, memantine of the same quantity as the members of group A. Differences in DPOAE amplitudes, and therefore in cochlear activity, between group A and group B were revealed. DPOAE amplitudes of group B were further reduced compared to the respective amplitudes in rabbits of group A. No improvement was observed in DPOAE measurements performed after the discontinuation of injections. The findings in group C should be examined separately. The measurements showed apparent reversal ototoxic effects in four of the animals. The development of aminoglycoside otoprotective strategies is a primary goal in ototoxicity research. The administration of NMDA antagonists has been shown to prevent, at least to some extent, toxic damage to hair cells in guinea pigs, treated with aminoglycoside antibiotics.

Role of Memantine in Limiting Cochleotoxicity in Rats.

Οur aim was to test whether amikacin's well-known cochleotoxic effects could be suppressed, depending on whether an NMDA-antagonist (memantine) was administered simultaneously with or after amikacin treatment. Forty Wistar rats were used in this experiment. Ten rats acted as controls and received no medication (group A). Amikacin (200 mg/kg) was administered intraperitoneally (i.p.) once daily for 14 days to 10 animals in group B; amikacin (200 mg/kg) was administered concurrently with memantine (10 mg/kg, i.p., once daily) to the same 10 animals in group C. Group D was given intraperitoneal memantine (10 mg/kg, once daily) for 14 days following a 2-week amikacin treatment. The cochlear activity of the right ear was tested using DPOAE in conscious animals. All animals were sacrificed at the conclusion of the experiment and both cochleae were collected for histological and immunohistochemical analysis. All groups treated with amikacin showed decreased cochlear activity, as testified by decreased DPOAE-amplitudes compared to the pre-treatment state. In the rats of group B, the DPOAE reduction was more pronounced. On histologic exam, the cochlear structures of group C rats and, although to a lesser extent, group D rats showed less severe cochlea damage. Memantine plays a protective role, resulting in restoring partially cochlear structures when administered either simultaneously with or after completion of amikacin i.p. treatment in rats.

Pregabalin abuse after past substance-seeking behavior.

Pregabalin is a prescription drug, structurally related to the neurotransmitter GABA. Following the rapidly increasing use of pregabalin, data signaling its abuse liability have been published recently. We report a case of a 19-year-old man with a history of cannabis and alcohol-seeking behavior that showed similar drug-seeking behavior with pregabalin. This report highlights the potential for abuse of pregabalin in patients with a history of substance-seeking behavior. Considering that the drug has recently been proposed as a treatment for alcohol- and benzodiazepine-dependence a better clarification of its abuse potential is essential.

Pharmacologic Stewardship in a Rural Community Pharmacy.

BACKGROUND: Pharmacotherapy is an essential part of patient care. In order to achieve optimal health outcomes, safe and effective prescribing and administering of medications is crucial, especially since the process of pharmacotherapy can cause serious problems, mainly adverse events and/or interactions, that often pass undetected. OBJECTIVE(S): To investigate the feasibility of using community pharmacies as checkpoints to detect errors and failures in prescribing, as well as patients' compliance with pharmacotherapy. To this end, analysis and recording of the prescribing process was carried out and error-prone points were identified. METHODS: Patients and caregivers filling prescriptions during the first 4 weeks of November 2017 and February 2018 answered questions in order to evaluate their attendance of regular checkups and their compliance with prescribing instructions. All prescriptions filled at the pharmacy were examined for detection of prescription errors and drug-drug interactions. Statistical analyses, including calculations of the correlation coefficient phi (φ), chi-square, and confidence intervals, were carried out. Detected errors and failures were evaluated by application of the Health Failure Mode Effect Analysis (HFMEA) quality tool. RESULTS: A significant number of patients (16.7%) failed to regularly attend checkups regarding known health problems (95% CI: 10.6-22.7%), a corresponding percentage (16%, 95% CI: 10.1-21.9%) did not comply with prescribed pharmacotherapy, and a significant proportion of patients self-medicated regularly (32%, 95% CI: 24.5-39.5%). A total of 8.6% of prescriptions included medication combinations with a potential for severe drug-drug interactions (95% CI: 7.1-10.2%) while 58.7% of the prescriptions included combinations that could lead to moderate ones (95% CI: 56.1-61.4). The HFMEA indicated that all problems recorded required immediate interventions, except for prescribing errors. CONCLUSIONS: Community pharmacies can be potential checkpoints for the detection and evaluation of prescribing errors and pharmacotherapy failures.

Efficacy and safety of parenteral and local application of tramadol in mandibular third molar extraction: a qualitative systematic review of current evidence.

PURPOSE: To assess the efficacy and safety of perioperative parenteral administration or submucosal infiltration of tramadol for perioperative pain control on the basis of pain intensity or analgesics consumption and perioperative outcomes in mandibular third molar surgery. MATERIAL-METHODS: An electronic database search was conducted up to 10 November 2022 to retrieve all randomized controlled trials (RCTs), assessing the analgesic efficacy of parenteral use of tramadol implemented as an adjunct to local anesthesia or intraoperative sedation/general anesthesia, in surgical extraction of mandibular third molars. Modified Jadad scale and Cochrane bias tool were used for the qualitative appraisal. RESULTS: Nineteen RCTs were selected for qualitative analysis. Nine studies involved intravenous, and 5 intramuscular administration of tramadol, while 5 evaluated submucosal infiltration with tramadol. Intravenous or intramuscular tramadol provided a weaker analgesic effect compared with non-steroidal anti-inflammatory drugs (NSAIDs), while intravenous tramadol induced an enhanced analgesic effect than oral tramadol. Parenteral administration of tramadol improved the quality of postoperative analgesia versus placebo. No notable adverse effects were recorded. CONCLUSIONS: Parenteral or submucosal infiltration of tramadol constitutes an effective and safe alternative analgesic approach in surgical extraction of mandibular third molars, yet the nociceptive effect of this analgesic modality could not supersede that of NSAIDs. TRIAL REGISTRATION: PROSPERO No CRD42021227574.

Salicylate- and Noise-induced Tinnitus. Different Mechanisms Producing the same Result? An Experimental Model.

PURPOSE: Tinnitus, the generation of phantom sounds, can be the result of noise exposure, however, understanding of its underlying mechanisms is limited. Purpose of the study was is to determine whether different concentrations of salicylate can cause tinnitus of different intensity. METHODS: For the purposes of this study 50 male Wistar rats were used. The animals were divided into 5 groups (10 rats in each group). The animals that did not receive any substance were allocated to the control group (Group A). The second group (Group B) of rats received salicylate (Sigma Aldrich) intraperitoneally for 7 days (300 mg/Kg/day). The 3rd group (Group C) received salicylate intraperitoneally for 7 days, but at twice the concentration of the animals in the second group (600 mg/kg/d). The 4th group (Group D) simultaneously received salicylate (300 mg/Kg/day) and pure Memantine (Sigma Aldrich, 10 mg/kg/d) intraperitoneally for 7 days. The 5th group (Group E) did not receive any substance but was exposed for 168 consecutive hours (7 days) to sound to induce tinnitus. Cochlear activity was evaluated with the use of Distortion Product Otoacoustic Emissions (DPOAEs). At the end of the experimental period, the animals were sacrificed, and the right cochlea was removed and prepared for further histological and immunohistochemical studies. RESULTS: The DPOAEs of animals treated either with salicylate as monotherapy or salicylate combined with memantine were indistinguishable from the noise floor, did not differ significantly compared to the animals of the control group or those expose to constant noise. The cochlear structures of Group E remained anatomically and functionally unaffected from the exposure to constant noise. Memantine does not seem to offer substantial protection to the cochlear structures, according to histological examination and hearing tests, however, the rats receiving it exhibited better results in behavioral tests. CONCLUSIONS: The administration of memantine does not contribute significantly to the reduction of tinnitus.

Contractile properties and movement behaviour in neonatal rats with axotomy, treated with the NMDA antagonist DAP5.

BACKGROUND: It is well known that axotomy in the neonatal period causes massive loss of motoneurons, which is reflected in the reduction of the number of motor units and the alteration in muscle properties. This type of neuronal death is attributed to the excessive activation of the ionotropic glutamate receptors (glutamate excitotoxicity). In the present study we investigated the effect of the NMDA antagonist DAP5 [D-2-amino-5-phosphonopentanoic acid] in systemic administration, on muscle properties and on behavioural aspects following peripheral nerve injury. METHODS: Wistar rats were subjected to sciatic nerve crush on the second postnatal day. Four experimental groups were included in this study: a) controls (injection of 0.9% NaCl solution) b) crush c) DAP5 treated and d) crush and DAP5 treated. Animals were examined with isometric tension recordings of the fast extensor digitorum longus and the slow soleus muscles, as well as with locomotor tests at four time points, at P14, P21, P28 and adulthood (2 months). RESULTS: 1. Administration of DAP5 alone provoked no apparent adverse effects. 2. In all age groups, animals with crush developed significantly less tension than the controls in both muscles and had a worse performance in locomotor tests (p < 0.01). Crush animals injected with DAP5 were definitely improved as their tension recordings and their locomotor behaviour were significantly improved compared to axotomized ones (p < 0.01). 3. The time course of soleus contraction was not altered by axotomy and the muscle remained slow-contracting in all developmental stages in all experimental groups. EDL, on the other hand, became slower after the crush (p < 0.05). DAP5 administration restored the contraction velocity, even up to the level of control animals 4. Following crush, EDL becomes fatigue resistant after P21 (p < 0.01). Soleus, on the other hand, becomes less fatigue resistant. DAP5 restored the profile in both muscles. CONCLUSIONS: Our results confirm that contractile properties and locomotor behaviour of animals are severely affected by axotomy, with a differential impact on fast contracting muscles. Administration of DAP5 reverses these devastating effects, without any observable side-effects. This agent could possibly show a therapeutic potential in other models of excitotoxic injury as well.

Prevalence of post-menopausal depression and associated factors: A web-based cross-sectional study in Greece.

OBJECTIVES: The impact of depression on post-menopausal women is an important public health issue but remains largely unknown. The purpose of this study was to identify the prevalence of post-menopausal depression in Greece and outline the profile of the women it affects. STUDY DESIGN: A sample of post-menopausal women completed an anonymous, self-administered, web-based survey which included the Beck Depression Inventory-ΙΙ (BDI-II) and questions regarding socio-demographic data. MAIN OUTCOME MEASURES: The dependent variable of interest was a BDI-II score ≥ 20 (the cut-off for moderate depression according to the BDI). RESULTS: Overall, 502 post-menopausal women participated in the study. The median BDI-II score was 13 (range 0-50); 136 (27.1%) of the women scored ≥ 20 and were considered screen-positive for depression. According to the multivariate logistic regression model, age< 55 years (OR: 1.621; 95% CI: 1.036-2.535), not working (OR: 1.580; 95% CI: 1.013-2.465), smoking (OR: 1.656; 95% CI: 1.081-2.536) and history of depression (OR: 1.650; 95% CI: 1.045-2.604) were independently associated with post-menopausal depression. Subgroup analyses revealed that current smokers (OR: 2.514; 95% CI: 1.485-4.256) had higher odds of moderate depression, while obesity (OR: 2.455; 95% CI: 1.206-4.996), absence of healthcare insurance (OR: 4.413; 95% CI: 1.970-9.887) and a history of depression (OR: 2.253; 95% CI: 1.212-4.190) were identified as independent risk factors for severe post-menopausal depression. CONCLUSIONS: More than one out of four post-menopausal women were screen-positive for symptoms indicative of depression, while a personal history of depression, age < 55 years, smoking and current working status were independent predictors of its emergence.