Clinical Utility of Melatonin in Fibromyalgia Diagnosis

       Fibromyalgia syndrome (FMS) is a chronic disease with an unknown etiology, which is characterized by reduced pain threshold (hyperallgesia) & pain with normally innocuous stimuli (allodynia).This diffuse pain is often disease associated  with wide range of  other symptoms including fatigue, sleep disturbance, stiffness& more.FMS often occur concomitantly  with other rheumatologic disease such as rheumatoid arthritis(RA), systemic lupus erthymatosus(SLE).       The pineal hormone melatonin (MT) exerts a variety of effects on the immune system. MT activates immune cells and enhances inflammatory cytokine and nitric oxide production.Methods: We were studied 75 subjects, 55 of subjects were FMS patients defined by the American Colleague of Rheumatology (ACR 2010) criteria. Patients' mean age was 32.5 ± 13.9 years. They were classified into two groups: Group I of 25  primary FMS patients . Group II of 30 secondary FMS patients with other rheumatologic disease such as RA, SLE. Twenty age and sex matched healthy individuals were included in the study as a control group.Results:Mean Melatonin titers were significantly reduced (p<0.0001) in primary FMs patients compared to the controls (21.32vs. 30.9 pg/ml), but they were significantly elevated (p<0.0001) in secondary FMS compared to controls (138.1vs.30.9 pg/ml). Our data imposed that, in 1ry FMS there were negative correlations of MT titers with tender points (r=-0.848**,p<0.0001), sleep disturbance(r=-0.963**, p< 0.0001**), Fatigue (r= -0.972**, p<0.001**), WPI (r= -0,953 **, p<0.0001) and SS (r=-0.901**, p< 0.0001). Conclusions:In primary FMS patients melatonin level is lower than melatonin level in control, but MT level is high in secondary FMS patients. There was a negative correlation between MT with tender points, sleep disturbance, fatigue, SS & WPI. But there was a positive correlation between MT & cognitive symptoms

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Echocardiographic predictors of atrial fibrillation after mitral valve replacement

Objectives: Detection of the echocardiographic predictors of post-operative atrial fibrillation in patients with rheumatic mitral valve disease undergoing mitral valve replacement. Methods: The study included 50 patients with rheumatic mitral valve disease undergoing mitral valve replacement. Preoperative assessment included standard two-dimensional echocardiography to assess LA diameter, volume, and emptying fraction, LV volume and ejection fraction. TDI derived velocity, strain of the left atrium and speckle tracking to assess left ventricular function then postoperative follow up for 1 month for occurrence of atrial fibrillation. Results: The incidence of postoperative AF was 44%; these patients were significantly older (P = 0.001) and show higher prevalence of DM (P = 0.001) and HTN (P = 0.001). Also, LA diameters (antero-posterior, transverse and longitudinal) and LA volumes (maximal and minimal) were increased (P  0.05). Systolic LA strain and left ventricular global longitudinal strain were significantly reduced in those patients (P value <0.001). Echocardiographic predictors of AF were LA systolic strain (P value <0.001) and LV global longitudinal strain (P value = 0.003). Cutoff value for systolic LA strain ≤23 had sensitivity 90.91% and specificity 93.33% in predicting POAF. While, left ventricular global longitudinal strain ≤−14.9% had sensitivity 63.6% and specificity 100.0% in predicting AF. Conclusion: LA systolic strain and LV global longitudinal strain were significant predictors of POAF. Echocardiographic parameters can identify patients at greater risk of developing POAF who can benefit from preventive measure and guide the selection of prosthesis

Sun-Exposed versus Sun-Protected Cutaneous Basal Cell Carcinoma: Clinico-Pathological Profile and p16 Immunostaining

Introduction: Although widespread, BCC is still relatively poorly understood in regards to pathogenesis and prognosis, particularly the lesions formed on anatomical sites away from sun exposure. With the aim of deepening our understanding of the pathogenesis and clinico-pathological correlations of BCCs, we conducted this study. Methods: Tissue blocks and data of 52 Egyptian patients diagnosed with BCC were retrieved for clinical information and inclusion criteria, then re-examined histologically; p16 immunostaining was carried out and evaluated for analysis and comparison between the two groups, i.e., sun-exposed and sun-protected. Results: Sex, age, clinical suspicion, tumor size, recurrence status, and histologic variants did not show a significant difference between the sun-protected and sun-exposed groups; however, the mean ages recorded were 67.2 vs. 62.7 for the sun-protected and sun-exposed groups, respectively. A total of 52% of BCCs were positive for p16. The sun-protected lesions showed p16 positivity in 61% of cases, whereas 49% of the sun-exposed lesions were positive with no significant difference. There was a significant difference in p16 expression between the recurrent and non-recurrent lesions. Conclusions: A significant difference was seen in the case of cancer recurrence, where all the recurrent BCCs in this study demonstrated negative p16 immunostaining of the primary lesions; however, the positively stained cases in total were 52% of BCCs. The mean patient age of the sun-protected group was much higher than in previous peer studies. We assume that the biological, prognostic, and clinical aspects of p16 protein expression in BCCs are still far from being clearly understood. Further studies are highly recommended, with more focus on its role in the pathogenesis and the prognostic factors

Optimization of a Fluorescence-Based Assay for Large-Scale Drug Screening against <i>Babesia</i> and <i>Theileria</i> Parasites

<div><p>A rapid and accurate assay for evaluating antibabesial drugs on a large scale is required for the discovery of novel chemotherapeutic agents against <i>Babesia</i> parasites. In the current study, we evaluated the usefulness of a fluorescence-based assay for determining the efficacies of antibabesial compounds against bovine and equine hemoparasites in <i>in vitro</i> cultures. Three different hematocrits (HCTs; 2.5%, 5%, and 10%) were used without daily replacement of the medium. The results of a high-throughput screening assay revealed that the best HCT was 2.5% for bovine <i>Babesia</i> parasites and 5% for equine <i>Babesia</i> and <i>Theileria</i> parasites. The IC₅₀ values of diminazene aceturate obtained by fluorescence and microscopy did not differ significantly. Likewise, the IC₅₀ values of luteolin, pyronaridine tetraphosphate, nimbolide, gedunin, and enoxacin did not differ between the two methods. In conclusion, our fluorescence-based assay uses low HCT and does not require daily replacement of culture medium, making it highly suitable for <i>in vitro</i> large-scale drug screening against <i>Babesia</i> and <i>Theileria</i> parasites that infect cattle and horses.</p></div

IC₅₀ values of the diminazene aceturate drug evaluated for <i>B</i>. <i>bovis</i> and <i>T</i>. <i>equi</i> with and without daily replacement of the medium using the fluorescence-based method.

<p>^a IC₅₀ values for diminazene aceturate were determined on the fourth day of <i>in vitro</i> culture using the fluorescence-based method with 2.5% and 5% HCTs for <i>B</i>. <i>bovis</i> and <i>T</i>. <i>equi</i>, respectively, in three separate experiments. Each drug concentration was made in triplicate in each experiment, and the final obtained IC₅₀s were the mean of three obtained values from separate experiments.</p><p>^b The differences between IC₅₀ values determined using the fluorescence-based method with and without daily replacement of the medium were not statistically significant.</p><p>IC₅₀ values of the diminazene aceturate drug evaluated for <i>B</i>. <i>bovis</i> and <i>T</i>. <i>equi</i> with and without daily replacement of the medium using the fluorescence-based method.</p

Growth inhibition of <i>B</i>. <i>bovis</i> and <i>T</i>. <i>equi</i> by diminazene aceturate estimated by the fluorescence-based method without daily replacement of the medium (black) and with daily replacement of the medium (gray).

<p>(A) Growth inhibition of <i>B</i>. <i>bovis</i> (y-axis) and log concentration of diminazene aceturate (nM) (x-axis). (B) Growth inhibition of <i>T</i>. <i>equi</i> (y-axis) and log concentration of diminazene aceturate (nM) (x-axis). Each value is presented as the mean of three triplicate wells ± SD after subtraction of the background fluorescence for non-parasitized RBCs.</p