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.

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.

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.

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.

Infliximab and Tocilizumab Reduce Anxiety-Like Behaviour and Improve Cognitive Performance in a Juvenile Collagen-Induced Arthritis Rat Model.

Anxiety disorders and cognitive decline are highly prevalent in rheumatic diseases, including Juvenile Idiopathic Arthritis (JIA). In this study, we investigated the effect of long-term treatment with infliximab and tocilizumab on anxiety-like behaviour and cognitive performance in a juvenile collagen-induced arthritis (CIA) rat model. Forty-nine rats with established moderate arthritis were randomly allocated into 7 equal groups: negative control, vehicle, methotrexate, infliximab, tocilizumab, methotrexate + infliximab and methotrexate + tocilizumab groups. Behavioural tests were performed to evaluate anxiety-like behaviour and cognitive function. Neuropathological changes were investigated by histological examination at the level of the hippocampus, the amygdala and the prefrontal cortex. Also, the expression of Brain-Derived Neurotrophic Factor (BDNF), a biomarker associated with neuronal survival and plasticity, was determined in the hippocampus and the amygdala by RT-qPCR. We found that both infliximab and tocilizumab reduced anxiety-like behaviour in the elevated-plus and elevated-zero maze tests. Tocilizumab, also, improved cognitive function in the olfactory social memory and passive avoidance tests. Anti-cytokine treatment reversed the histopathological changes in the brain induced by CIA. BDNF expression was higher in all treatment groups and especially those receiving monoclonal antibodies combined with methotrexate. Our data provide evidence that chronic infliximab and tocilizumab treatment reduces anxiety-like behaviour, improves cognitive function, reverses neuropathological changes and increases central BDNF expression in a juvenile arthritis rat model. These findings may be translated to humans to address behavioural comorbidities associated with 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.

Modulation of nociception and pain-evoked neurobehavioral responses by levetiracetam in a craniotomy pain model.

Traditional and novel analgesic modalities have been extensively tested for post-craniotomy pain management, yet the role of newer antiepileptic drugs in this area remains obscure. This study investigates the impact of levetiracetam (LEV) on pain modulation and neurobehavioral performance in a craniotomy model. Fifty-six Wistar rats were randomly assigned into seven groups: no intervention (CTRL), administration of placebo or LEV with no further intervention (PBO and LEV, respectively), and sham-operation or craniotomy in placebo (PBO-SHAM and PBO-CR, respectively) or LEV-treated rats (LEV-SHAM and LEV-CR, respectively). Pain was assessed by the rat grimace scale before, and at 8 and 24 h after craniotomy, following intraperitoneal injections of LEV (100 mg/kg twice daily) or normal saline two consecutive days before and on the craniotomy day. Elevated plus-maze and olfactory social memory tests were performed at 24- and 48 h post-craniotomy, respectively. Upon testing conclusion blood samples were collected for cytokines estimation. Levetiracetam administration enhanced antinociception in sham and craniotomy groups. In the elevated plus-maze test, LEV-CR rats spent more time in investigating open arms and performed more open arm entries than PBO-SHAM and PBO-CR animals. The olfactory test revealed no between-groups difference in acquisition time during first contact with a juvenile rat, while LEV-CR rats spent less time to recognize the same juvenile rat compared to PBO-SHAM and PBO-CR groups. Furthermore, LEV-treatment attenuated cortisol, interleukin-6 and TNF-a release, in sham and craniotomy animals. In conclusion, preemptive use of LEV decreases nociception, improves pain-evoked behavior and attenuates stress response in rats subjected to craniotomy.

Effects of long-term infliximab and tocilizumab treatment on anxiety-like behavior and cognitive function in naive rats.

BACKGROUND: Circulating cytokines have been proposed to be implicated in the development of mood disorders and cognitive impairment. This study aims to examine the effect of chronic treatment with infliximab, a tumor necrosis factor-alpha (TNF-alpha) inhibitor, and tocilizumab, an antibody against interleukin-6 (IL-6) receptor on anxiety-like behavior and cognitive function. METHODS: Twenty-eight male, Wistar rats were randomly allocated into negative control, vehicle, infliximab and tocilizumab groups. After 8 weeks of intraperitoneal drug administration, rats performed the elevated-plus maze, the elevated-zero maze, the olfactory social memory and the passive avoidance tests. Brain sections at the level of the hippocampus, the amygdala and the prefrontal cortex were histologically examined. Finally, hippocampal and amygdaloid brain-derived neurotrophic factor (BDNF) expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Infliximab group exhibited a significantly higher number of entries and time spent into the open arms of the mazes, showing a lower level of anxiety. In the olfactory social memory test, tocilizumab significantly increased the ratio of interaction. Both infliximab- and tocilizumab-treated animals had a significantly lower latency time in the passive avoidance test that suggests an improved memory. Histological examination revealed similar morphology and neuronal density between groups. BDNF expression levels were significantly increased in the groups receiving anti-cytokine treatment. CONCLUSIONS: Our findings suggest that long-term peripheral TNF-alpha and IL-6 inhibition improves anxiety and cognitive function in rats and leads to an increased BDNF expression in the brain.

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.

Ibuprofen and COVID-19 disease: separating the myths from facts.

Introduction: The Coronavirus disease 2019 (COVID-19) poses novel challenges in the healthcare systems around the world. Concern about the role of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and, in particular, ibuprofen has led to significant speculation.Areas covered: A literature search was conducted to evaluate ibuprofen's potential benefits and harms in the COVID-19 disease. Angiotensin-Converting Enzyme 2 (ACE-2) is crucial entry receptor for Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) in host cells. We found no scientific evidence linking ibuprofen use and an ACE-2 overexpression. Ibuprofen suppresses the production of various pro-inflammatory cytokines that are implicated in the 'cytokine storm' and subsequent ARDS in COVID-19 disease. Nevertheless, the exact role of ibuprofen in the immune response in COVID-19 disease is still unknown. There are no double-blind, placebo-controlled studies assessing the effect of ibuprofen on COVID-19 disease progression.Expert opinion: The studies that have been performed so far demonstrate no association between ibuprofen use and increased mortality rates or an increased risk for respiratory support. Accordingly, we recommend ibuprofen to be used for managing COVID-19 symptoms.

Infliximab and tocilizumab reduce anxiety-like behavior, improve cognitive performance and reverse neuropathological alterations in juvenile rats with severe autoimmune arthritis.

Several studies have demonstrated that rheumatic diseases, including Juvenile Idiopathic Arthritis (JIA), are associated with anxiety-like behavior and a cognitive decline. Infliximab, a Tumor Necrosis Factor-alpha (TNF-a) inhibitor, and tocilizumab, an antibody against Interleukin-6 (IL-6) receptor, are commonly used in the treatment of JIA. Here, we aimed to evaluate the effects of infliximab and tocilizumab on anxiety symptoms and cognitive function in a juvenile model of severe autoimmune arthritis. We found that both infliximab and tocilizumab improved anxiety-like behavior in the elevated-plus and elevated-zero maze tests. Tocilizumab, also, improved cognitive performance in the passive avoidance and olfactory social memory tests. Histological examination showed that anti-cytokine treatment reversed the histopathological alterations in the brain induced by arthritis. Further, infliximab and tocilizumab treatment increased Brain-Derived Neurotrophic Factor (BDNF) expression in the hippocampal and amygdaloid area of rat brain. In summary, our findings provide evidence that infliximab and tocilizumab have a beneficial effect on anxiety-like behavior and cognitive function and alleviate neuropathological alterations in a juvenile rat model of severe arthritis, suggesting that inhibition of TNF-a and IL-6 in the periphery, may be associated with a mood and memory enhancement in JIA patients.

Effects of Long-Term Methotrexate, Infliximab, and Tocilizumab Administration on Bone Microarchitecture and Tendon Morphology in Healthy Wistar Rats.

Objective Rheumatic diseases are associated with bone loss, both systemic and periarticular, and tendon abnormalities. The aim of this study is to examine the effect of three antiarthritic drugs, methotrexate, an anti-folate metabolite; infliximab, a Tumor Necrosis Factor-alpha (TNF-α) inhibitor; and tocilizumab, an antibody against Interleukin-6 (IL-6) receptor, on bone microarchitecture and tendon morphology in the absence of an inflammatory state. Materials and methods Thirty-five, 8- to 9-week-old, male, Wistar rats were randomly allocated into five groups: negative control (CTRL), vehicle (VEH), methotrexate (MTX), infliximab (INFX), and tocilizumab (TCZ). After 8 weeks of antiarthritic drug intraperitoneal administration, animals were euthanized and rat tibiae and patellar tendons were histologically examined. Results All sections exhibited normal bone microarchitecture. Histological scores in all groups corresponded to normal bone mineral density. No no apparent differences in tenocyte morphology and architecture of collagen fibers were observed. Conclusions The results of this study indicate that long-term administration of methotrexate, infliximab, and tocilizumab had no effect on bone microarchitecture and tendon morphology in rats in the absence of an inflammatory condition.

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.

An Improved Method for Isolating High-Quality RNA From Rat Bone at Room Temperature Without the Need for Specialized Equipment.

Research on bone diseases often requires investigation of bone gene expression. Isolating high-quality RNA is essential to obtain reliable and accurate gene expression data. In an effort to analyze the expression of genes related to osteoporosis in rat bones, we developed an improved method for extraction of high-quality RNA without the need for liquid nitrogen or specialized equipment. This method involved transitioning frozen bone tissues to a more pliable state with RNAlater ice and pulverization of the samples with a simple homogenizer, followed by a phenol-chloroform-based RNA extraction. Spectrophotometric analysis indicated high purity of the isolated RNA. Electrophoresis on agarose gel revealed two well-defined ribosomal RNA bands. Herein, we present a method that consistently yields RNA of high purity and integrity from rat bone.

Improved strategies to counter the COVID-19 pandemic: Lockdowns vs. primary and community healthcare.

COVID-19 pandemic mitigation strategies are mainly based on social distancing measures and healthcare system reinforcement. However, many countries in Europe and elsewhere implemented strict, horizontal lockdowns because of extensive viral spread in the community which challenges the capacity of the healthcare systems. However, strict lockdowns have various untintended adverse social, economic and health effects, which have yet to be fully elucidated, and have not been considered in models examining the effects of various mitigation measures. Unlike commonly suggested, the dilemma is not about health vs wealth because the economic devastation of long-lasting lockdowns will definitely have adverse health effects in the population. Furthermore, they cannot provide a lasting solution in pandemic containment, potentially resulting in a vicious cycle of consecutive lockdowns with in-between breaks. Hospital preparedness has been the main strategy used by governments. However, a major characteristic of the COVID-19 pandemic is the rapid viral transmission in populations with no immunity. Thus, even the best hospital system could not cope with the demand. Primary, community and home care are the only viable strategies that could achieve the goal of pandemic mitigation. We present the case example of Greece, a country which followed a strategy focused on hospital preparedness but failed to reinforce primary and community care. This, along with strategic mistakes in epidemiological surveillance, resulted in Greece implementing a second strict, horizontal lockdown and having one of the highest COVID-19 death rates in Europe during the second wave. We provide recommendations for measures that will reinstate primary and community care at the forefront in managing the current public health crisis by protecting hospitals from unnecessary admissions, providing primary and secondary prevention services in relation to COVID-19 and maintaining population health through treatment of non-COVID-19 conditions. This, together with more selective social distancing measures (instead of horizontal lockdowns), represents the only viable and realistic long-term strategy for COVID-19 pandemic mitigation.

Exploring a Safety Signal of Antipsychotic-Associated Pneumonia: A Pharmacovigilance-Pharmacodynamic Study.

An association between antipsychotic drugs and pneumonia has been demonstrated in several studies; however, the risk for pneumonia caused by specific antipsychotics has not been extensively studied. The underlying mechanism is still unknown, and several receptor mechanisms have been proposed. Therefore, using a combined pharmacovigilance-pharmacodynamic approach, we aimed to investigate safety signals of US Food and Drug Administration (FDA)-approved antipsychotics for reporting pneumonia and the potential receptor mechanisms involved. A disproportionality analysis was performed to detect a signal for reporting "infective-pneumonia" and "pneumonia-aspiration" and antipsychotics using reports submitted between 2004 and 2019 to the FDA adverse events spontaneous reporting system (FAERS) database. Disproportionality was estimated using the crude and the adjusted reporting odds ratio (aROR) and its 95% confidence interval (CI) in a multivariable logistic regression. Linear regressions investigated the relationship between aROR and receptor occupancy, which was estimated using in vitro receptor-binding profiles. Safety signals for reporting infective-pneumonia were identified for clozapine (LL = 95% 3.4, n = 546 [aROR: 4.8]) as well as olanzapine (LL = 95% 1.5, n = 250 [aROR: 2.1]) compared with haloperidol, while aRORs were associated with higher occupancies of muscarinic receptors (beta = .125, P-value = .016), yet other anti-muscarinic drugs were not included as potential confounders. No safety signals for reporting pneumonia-aspiration were detected for individual antipsychotics. Multiple antipsychotic use was associated with both reporting infective-pneumonia (LL 95%: 1.1, n = 369 [aROR:1.2]) and pneumonia-aspiration (LL 95%: 1.7, n = 194 [aROR: 2.0]). Considering the limitations of disproportionality analysis, further pharmacovigilance data and clinical causality assessment are needed to validate this safety signal.

The Administrative Prevalence of Multiple Sclerosis in Greece on the Basis of a Nationwide Prescription Database.

Objective: To estimate current prevalence of multiple sclerosis (MS) in Greece using administrative data from the nationwide medicine prescription database. Methods: Prescription records of a 24-month period (June 2017-May 2019) were analyzed in order to identify cases of MS. Sex, age, and place of residence were recorded for each identified case. Prevalence of MS was calculated based on the updated records of the Greek population according to Hellenic Statistical Authority. Results: The 2-year cumulative period prevalence of MS was estimated to 197.8 per 100,000 (95% CI 197.6-198.0). In total, 21,218 patients (65.8% female) were identified. During this period, the prevalence of MS was 138.7 per 100,000 (95% CI 138.4-139.0) in men and 253.6 per 100,000 (95% CI 253.3-254.1) in women. Prevalence was higher in the 45-49 age group in both sexes. Analysis of the place of residence revealed higher prevalence in the Attica region and Western Greece while lower prevalence was observed in Northern Greece. No north-south latitude gradient was detected. Point prevalence on 1 January 2019 was calculated to 188.9 per 100,000 (95% CI 188.7-189.1). Regarding treatment, 73.1% of the identified cases received at least once a Disease Modifying Drug. Conclusions: According to this national-level study conducted in Greece, estimated prevalence of MS was found to be similar to those of other European countries. Heterogeneity of MS prevalence across the country was observed and needs further investigation.

Reduced pain and analgesic use after acoustic binaural beats therapy in chronic pain - A double-blind randomized control cross-over trial.

BACKGROUND: Binaural Beats (BB) consist of two artificial acoustic stimuli with different frequency, presented simultaneously but independently to each ear. The human brain perceives and synchronizes to this frequency difference (entrainment). Aim of this study was to test the hypothesis that brain entrainment to a lower function rhythm, with BB application, can decrease pain perception and analgesic medication use, in chronic pain patients. METHODS: In a double blind, randomized, cross-over trial, BB at 5Hz (theta rhythm) were applied for 30 minutes, under simultaneous electroencephalogram recordings, followed by liberal, on demand use by chronic pain patients for a week, compared to sham stimulation (SS). Pain as the main outcome (numeric scale, NRS), stress (STAI) and medication usage (defined daily doses, DDD) were assessed at baseline, 30 minutes and week's end. RESULTS: Perceived pain (NRS) was significantly reduced in BB intervention (5.6±2.3 to 3.4±2.6, p<0.001), compared to SS (5.2±2.1 to 4.8±2.3, p=0.78), during the first 30-minute phase, as well as at the week's end (to 3.9±2.5 compared to 5.5±2.6 respectively, p<0.001). The mean EEG theta power at 5Hz was significantly increased only during BB application. Stress was significantly reduced at 30 minutes in both interventions but remained reduced only in the BB group at the week's end. Analgesic medication consumption (DDD, g) during the week was significantly less in the BB intervention (3.9±3.7 vs. 4.6±4.1, p<0.05), while reporting equal to SS mean levels of pain. CONCLUSIONS: Acoustic BB reduced pain intensity, stress and analgesic use, compared to SS, in chronic pain patients. SIGNIFICANCE: This study provides evidence that theta rhythm binaural beats can alleviate pain intensity, both after a brief 30 minute and a longer one week on-demand intervention. The subsequent significant reduction in analgesic medication consumption in chronic pain patients' daily living could offer a valuable tool, augmenting the effect of existing pain therapies.