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The aims of this paper were to provide an overview of available activity monitors used in research in patients with heart failure and to identify the key criteria in the selection of the most appropriate activity monitor for collecting, reporting, and analysing physical activity in heart failure research. This study was conducted in three parts. First, the literature was systematically reviewed to identify physical activity concepts and activity monitors used in heart failure research. Second, an additional scoping literature search for validation of these activity monitors was conducted. Third, the most appropriate criteria in the selection of activity monitors were identified. Nine activity monitors were evaluated in terms of size, weight, placement, costs, data storage, water resistance, outcomes and validation, and cut-off points for physical activity intensity levels were discussed. The choice of a monitor should depend on the research aims, study population and design regarding physical activity. If the aim is to motivate patients to be active or set goals, a less rigorously tested tool can be considered. On the other hand, if the aim is to measure physical activity and its changes over time or following treatment adjustment, it is important to choose a valid activity monitor with a storage and battery longevity of at least one week. The device should provide raw data and valid cut-off points should be chosen for analysing physical activity intensity levels. Other considerations in choosing an activity monitor should include data storage location and ownership and the upfront costs of the device. Funding Agencies|European Society of Cardiology Funding Source: Medline

Background and aim: The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) aims to further develop its role in international medical and scientific guidance in the field of Clinical Microbiology and Infectious Diseases, where many types of guidance documents exist. The ESCMID Executive Committee and the Clinical Microbiology and Infection (CMI) editorial board wish to clarify the terminology and format to be used in ESCMID guidance documents submitted for publication in CMI, and to highlight the principles behind ESCMID guidance documents.Types of guidance documents: There are five types of ESCMID guidance documents: White Papers, Clinical Practice Guidelines, Consensus Statements, State-of-the-Science Statements, and Position Papers. They differ in scope, methods of development, drafting group composition and preferred publication format. Guidance documents can be proposed, developed and published by ESCMID Study Groups, Committees and individual members; often, other scientific societies are involved. The full disclosure of potential conflicts of interest of all drafting group members is a requirement.Final remarks: Guidance documents constitute a common cultural and scientific background to people in the same and related professions. Also, they are an important educational and training tool. Developing a guidance document is a scientific endeavour, where a sound and transparent development process is needed, requiring multidisciplinary and personal skills. (C) 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Objectives: The study investigated the difficulties experienced by endodontics researchers around the world in conducting studies and writing papers. Materials and Methods: A survey consisting of 18 questions on the difficulties experienced by endodontics researchers in performing studies and writing papers was e-mailed to academics in the field of endodontics working at 202 universities. The independent risk factors were analyzed using binary logistic regression at a significance level of 0.05. Results: A total of 581 individuals (10.7%) agreed to participate in the study. Almost half the participants (48.2%) reported that they had received some type of training in conducting studies and writing papers. In response to the question, “Do you get help from a statistician to perform the statistical analyses of your studies?,” 77.1% answered “yes.” Around 40% of the participants stated that the need to obtain ethical approval negatively affected their desire to conduct studies. The participants’ regions had no effect on the reported difficulties associated with writing papers in English or conducting statistical analyses (p > 0.05). Most participants (81.8%) reported difficulties in writing the Discussion section, regardless of their region, academic degrees, or years of experience. Conclusions: The participants stated they experienced difficulties in many areas, such as conducting statistical analyses, finding new ideas, and writing in English. Engaging in a detailed examination of ethics committee rules, expanding biostatistics education, increasing the number of institutions providing research funding, and increasing the number of endodontics journals can increase the enthusiasm of endodontics researchers to publish papers.

Osler demonstrated two cultures in his practice, in accordance with the conventions of his time: humanity and science. He was aware that ill health is best managed by one who is both ‘a scientist and a humanist in one’. (This was the title of seminars that took place at 13 Norham Gardens Oxford, his former home, to celebrate the Osler centenary. See figure 1.) In terms of humanity, his friendliness was itself therapeutic. As for science, his accurate observations of symptoms in the living, and of signs in both the living and dead, were more numerous. well described and analysed than ever before. Those who state nowadays that there are two separate cultures that do not speak to each other should recall Osler’s last communication to be published in the British Medical Journal: ‘The old humanities and the new science’.1 Here, he complained himself that the culture of humanities in Oxford, while embracing the philosophy of ancient Greeks, was giving too little attention to their contributions to science. Later, CP Snow2 and others such as the American philanthropist John McGovern3 discussed how these two cultures should both be embraced by practicing physicians I will reinterpret these as the ‘attitude of care’ and the ‘technology of care’. Osler was the greatest exponent of both in his time, deserving the claim that he was both a bringer of cheer and a scientist in what he brought to the bedside, rather more than most of his contemporaries. Figure 1 13 Norham Gardens, built in 1870. Much has been written about Osler the clinician and it is no longer easy to find something new to say. One such attempt was in a recent article by a contemporary student of ethics and his supervisor in Melbourne, Fiddes and Komesaroff was entitled ‘An emperor …

William Osler wrote more than a dozen books and over 750 articles in his lifetime, but one book and one article are by far the best known. ‘Principles and Practice of Medicine’ was published in 1892 and was a huge success. It went through 17 editions and established a model for textbooks of general medicine to the present day. The enduring fame of his short piece entitled ‘Aequanimitas’,1 composed 3 years earlier, might have surprised him more. It was the transcript of an address he gave to new medical graduates at the University of Pennsylvania. It also served as his farewell lecture before he departed to become chief of staff at Johns Hopkins Hospital. Reading it now, it seems in some ways very much from a bygone age. Osler assumes, for example, that every member of his audience will have a comfortable familiarity with classical literature, the Bible and Shakespeare. The first paragraph alone contains at least five references to the classics, including the tale of Er the Pamphylian from Plato’s Republic. Later, he reminds his audience that the word ‘aequanimitas’ (‘equanimity’) was used by the benign Roman emperor Antoninus Pius on his deathbed, as his choice of the day’s military password. He would have taken it for granted that all his students knew the word meant ‘calmness of soul’, from the Latin words ‘aequus’ and ‘animus’. It is not a style that would appeal to many new medical graduates today. The first three pages do not mention equanimity at all but cover a related quality, imperturbability. His approach is striking because of his insistence that imperturbability is largely a physical endowment, or in other words genetic. According to Osler, you either have it or you do not. …

Objective To survey the knowledge, attitude, and practices of Vietnamese pharmacists regarding the COVID-19 pandemic. Method This cross-sectional, paper-based study was conducted from June to August 2020. A validated questionnaire (Cronbach’s alpha = 0.84) was used to interview 1,023 pharmacists in nine provinces of Vietnam. Analysis of covariance was employed to identify factors associated with the knowledge of pharmacists. The best model was chosen by using the Bayesian Model Averaging method in R software version 4.0.4. Results The mean knowledge score was 12.02 ± 1.64 (range: 6–15), which indicated that 93.4% of pharmacists had good knowledge of COVID-19. There was no difference in the average score between males and females (p > 0.05). The multivariate linear regression model revealed that the knowledge was significantly associated with pharmacists’ age, education level, and residence (p < 0.001). About attitude and practices, pharmacists daily sought and updated information on the COVID-19 pandemic through mass media and the internet (social network and online newspapers). Nearly 48% of them conceded that they communicated with customers when at least one person did not wear a face mask at the time of the COVID-19 outbreak. At medicine outlets, many measures were applied to protect pharmacists and customers, such as equipping pharmacists with face masks and hand sanitizers (95.0%), using glass shields (83.0%), and maintaining at least one-meter distance between two people (85.2%). Conclusion The pharmacists’ knowledge of COVID-19 transmission, symptoms, and prevention was good. Many useful measures against the spread of this perilous virus were applied in medicine outlets. However, pharmacists should restrict forgetting to wear face masks in communication with medicine purchasers. The government and health agencies should have practical remedies to reduce the significant differences in the COVID-19 knowledge of pharmacists among provinces and education-level groups.

The most oral surgical interventions require primary wound closure with stitches after previously raised mucoperiosteal flap. Different suture materials are used for this purpose which are classified upon their origin (organic and synthetic) or according to their durability in host tissues (absorbable and non-absorbable). The aim of the review paper was to emphasize the all-important properties of suture material include knot safety, stretch capacity, tissue reactivity, and wound safety. MEDLINE and PubMed databases were explored from the 1970 up to 2018 using the keywords in different combinations: oral surgery, suture material, flap, dental implants, nylon, periodontal, polyglecaprone, polytetrafluoroethylene, polyglycolic acid, polylactic acid, silk. Normal wound healing after oral surgery procedures requires multiple finely tuned processes that occur in a specific sequence as well as proliferation, regeneration and organization (differentiation). The final stage of the wound healing process is named the contraction phase, which begins following sufficient collagen formation in the granular tissue. Traditionally, silk has been the mostly used as suture material for oral surgical procedures, with rarely including others as: nylon, polyester, cat gut, polytetrafluoroethylene (ePTFE), polyglycolic acid (PGA) etc. Surgery with silk sutures increases the risk of infections because they react with the connective tissue, causing adhesion of dental plaque and bacteria adherence around the stitch. On the other hand, a specific form of wound healing occurs around placed dental implants. Usually the implants are placed directly under or at the same level as the bone surface at biphasic dental implant procedures. In conclusion, besides the carefully used surgical and suturing technique, and properly oral hygiene in the postoperative period, the choice of suture material may also influence the healing of the incised soft tissues. Thus the selection of the suture material should be brought under consideration during treatment planning for oral surgical interventions, periodontal surgery and dental implantation. Key words: Oral, Surgery, Periodontal, Implants, Flap, Suture, Silk, Nylon.

In his life of Sir William Osler, the historian Michael Bliss wrote ‘To a modern biographer, searching for the feet of clay that make subjects credible, the remarkable unanimity of the sources is disconcerting’.1 The sources that Bliss referred to here included not only doctors who were almost as distinguished as Osler, like Harvey Cushing, but everyone else from medical students to cabinet ministers. Osler seems to have been one of those rare individuals who combined an astonishing level of professional achievement with personal warmth and kindness. It is hard if not impossible to disagree with his biographer’s overall judgement: ‘He …

Sir William Osler, born on 12th July 1849 and died on 29th December 1919, is often called the ‘Father of Modern Medicine’. Born and raised in Canada, he graduated from McGill University and took up important posts in Philadelphia, Baltimore and Oxford. He left his mark on all these places and so in the centenary of this death, he is commemorated widely for his legacy to the practice of medicine and the training of medical doctors. The Postgraduate Medical Journal is proud to dedicate the current issue to the memory of the great …

Improved medical care of congenital heart disease patients increased survival into adulthood from 15% in the 1960s to over 85% in the current era. As a consequence, the prevalence of adult congenital heart disease (ACHD) increased rapidly,1 which is estimated to be >1 million ACHD patients in North America and 1.2 million in Europe. The growing number and aging of ACHD patients led to an overall increase in hospitalizations over the last decade and a substantial increase in patients presenting with heart failure (HF) (∼20%).2 The incidence of first HF-admission was 1.2 per 1000 patient-years in the Dutch national ‘CONCOR’ registry. Patients admitted with HF had a five-fold higher risk of death than those not admitted. From the same registry, the mortality was 2.8% during a follow-up period of 24 865 patient-years. Chronic HF (26%) and sudden death (19%) were recorded most frequently. The median age at death from HF was 51.0 years (range: 20.3–91.2 years).3 In another ACHD cohort, sudden death (26%) was the most common cause of death, followed by progressive HF (21%) and perioperative death (18%).4 Although patients with ACHD may not readily report symptoms, clinical HF is documented in 22.2% of patients with a Mustard repair for transposition of the great arteries (TGAs), 32.3% with congenitally corrected transposition of the great arteries (ccTGA), and 40% of patients after Fontan palliation. ### Heart failure with impaired systolic ventricular function The aetiology and triggers of impaired systolic ventricular function in ACHD patients are summarized in Table 1 . View this table: Table 1 Pathophysiology of heart failure with impaired systolic function: triggers (examples) ### Heart failure with preserved systolic ventricular function This occurs less often in ACHD patients, but is associated with specific conditions such as Shone complex and restrictive …

Moderate-to-severe psoriasis is associated with significant comorbidity, an impaired quality of life, and increased medical costs, including those associated with treatments. Systematic reviews (SRs) and meta-analyses (MAs) of randomized clinical trials are considered two of the best approaches to the summarization of high-quality evidence. However, methodological bias can reduce the validity of conclusions from these types of studies and subsequently impair the quality of decision making. As co-authorship is among the most well-documented forms of research collaboration, the present study aimed to explore whether authors' collaboration methods might influence the methodological quality of SRs and MAs of psoriasis. Methodological quality was assessed by two raters who extracted information from full articles. After calculating total and per-item Assessment of Multiple Systematic Reviews (AMSTAR) scores, reviews were classified as low (0-4), medium (5-8), or high (9-11) quality. Article metadata and journal-related bibliometric indices were also obtained. A total of 741 authors from 520 different institutions and 32 countries published 220 reviews that were classified as high (17.2%), moderate (55%), or low (27.7%) methodological quality. The high methodological quality subnetwork was larger but had a lower connection density than the low and moderate methodological quality subnetworks; specifically, the former contained relatively fewer nodes (authors and reviews), reviews by authors, and collaborators per author. Furthermore, the high methodological quality subnetwork was highly compartmentalized, with several modules representing few poorly interconnected communities. In conclusion, structural differences in author-paper affiliation network may influence the methodological quality of SRs and MAs on psoriasis. As the author-paper affiliation network structure affects study quality in this research field, authors who maintain an appropriate balance between scientific quality and productivity are more likely to develop higher quality reviews.

WOS: 000356799600005, PubMed ID: 25999021, Acute heart failure is a fatal syndrome. Emergency physicians, cardiologists, intensivists, nurses and other health care providers have to cooperate to provide optimal benefit. However, many treatment decisions are opinion-based and few are evidenced-based. This consensus paper provides guidance to practicing physicians and nurses to manage acute heart failure in the pre-hospital and hospital setting. Criteria of hospitalization and of discharge are described. Gaps in knowledge and perspectives in the management of acute heart failure are also detailed. This consensus paper on acute heart failure might help enable contiguous practice., Bayer; Cardiorentis; Medicine Company; Critical Diagnostics; Novartis; Steering Committee member of Cardiorentis; TUBITAK; Medicines Company; Cornerstone Therapeutics; Otsuka; Janssen; Apex Innovations; Inte-Section Medical; Trevena; Vifor Pharma Ltd; Amgen; Servier; Abbott Vascular; Coridea; Respicardia; Swiss National Science Foundation; Swiss Heart Foundation; Cardiovascular Research Foundation Basel; 8sense; Abbott; ALERE; Brahms; Nanosphere; Roche; Siemens; University Hospital Basel; Astra Zeneca; BG medicine; Biomerieux; Lilly; Orion; Resmed; Roche Diagnostics; Ratiopharm; BMS; Boehringer-Ingelheim; Pfizer; Daiichi Sankyo; Boehinger Ingelheim; AstraZeneca; European Union, A.M. received speaker's honoraria from Alere, Bayer, Edwards Life Sciences, The Medicines Company, Novartis, Orion, Servier, Thermofisher, Vifor Pharma and also received fee as member of advisory board and/or Steering Committee from Bayer, Cardiorentis, The Medicine Company, Critical Diagnostics.; M.B.Y. received speaker's honoraria and research fee from Novartis and received fee as Steering Committee member of Cardiorentis, and is supported by TUBITAK.; P.L. received speaker's honoraria from Beckman Coulter and Novartis and also received fees as a member of advisory board and/or Steering Committee from Bayer, Cardiorentis, The Medicines Company, Cornerstone Therapeutics, Novartis, Otsuka, Janssen, Apex Innovations, Inte-Section Medical, and Trevena.; P.P. received speaker's honoraria from Bayer, Novartis, Servier, Vifor Pharma, Amgen, Pfizer, Cardiorentis, Merck-Serono, Abbott Vascular and Respicardia and also received fee as member of advisory board and/or Steering Committee from Bayer, Cardiorentis, Novartis, Vifor Pharma Ltd, Amgen, Servier, Abbott Vascular, Coridea and Respicardia.; E.L. received consultancy fee from Novartis.; J.M. received honoraria for speaker or advisor from Abbott, Novartis, Orion, Otsuka, and Sanofi and fee as a member of Steering Committee from Corthera, Novartis, and Cardiorentis.; C.M. received research grants from the Swiss National Science Foundation and the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, 8sense, Abbott, ALERE, Brahms, Critical Diagnostics, Nanosphere, Roche, Siemens, and the University Hospital Basel, as well as speaker/consulting honoraria from Astra Zeneca, Abbott, ALERE, BG medicine, Biomerieux, Brahms, Cardiorentis, Lilly, Novartis, Pfizer, Roche, and Siemens.; V.P.H. received speaker's fee: Bayer, Orion, Resmed, Roche Diagnostics, Ratiopharm; consultation fees: Bayer, BMS, Boehringer-Ingelheim, Novartis, Pfizer, Roche Diagnostics, Servier. H.A.T. received speaker's honoraria from Daiichi Sankyo, Lilly, Medicines Company, AstraZeneca, Boehinger Ingelheim. Advisory board for Maquet Cardiovascular. Institutional research support by Maquet Cardiovascular, Teleflex, Terumo, Lilly, The Medicine Company.; G.F. has received research grants and/or has served as Committee member or Cochair of studies sponsored by Bayer, Novartis, Cardiorentis, Vifor Pharma, and the European Union.

We performed a systematic survey of original papers published in The Lancet throughout the years 1945, 1946, 1970 and 1995. The Lancet was chosen due to a conservative layout through these years, and the year 1946 added to the analysis to ponder for any war-induced bias. The general layout and structure of the journal were indeed maintained throughout these years. The number of authors per paper increased steadily (from 1.7±1.3 in 1945 to 6.4±3.4 in 1995), as well as the number of papers written on behalf of investigation groups (from 1 in 1945 to 37 in 1995). Major changes were observed in the area of origin of the papers, from an overwhelming British Isles' preponderance (87% of papers published in 1945) to a partake with Continental Europe, America and international groups (27, 33, 15 and 12%, respectively of the 1995 papers). The most often addressed fields of medicine shifted from war-, surgery- and microbiology-related subjects in 1945 towards cardiology-, oncology-, and virus-related works in 1995. The most impressive and enduring change was the increase in the use of statistical tools for data analysis and presentation (0.3% of papers in 1945 vs. 60% in 1995). As one of the leading medical journals with a maintained layout over the last decades, The Lancet reflects changes in medical thinking and publishing. Multiauthorship, internationalisation of research, and (over) confidence into statistical analysis are becoming leading characteristics, some rather positive others not, of the corporate feeling within medical edition.

Access to the vascular system has been one of the major factors limiting the application of haemodialysis for the treatment of kidney failure. The history of vascular access parallels the development of dialysis technology. The celloidin-tubing dialysis machine by Abel et al. used glass cannulas that were perfectly apt for that milestone proof of concept study which demonstrated that haemodialysis can remove diffusible solutes from living animals [1, 2]. The Kolff dialyzer initially used a more much laborious procedure [3]. Blood had to be taken by venipuncture in 50-mL aliquots, dialyzed and returned to the patient. This was a lengthy, time-consuming procedure and the urgent need of developing continuous-flow methods was evident since the early days of dialysis. Artery and vein cannulation and heparin anti-coagulation offered a first solution for the successful application of haemodialysis as treatment of acute renal failure. With this approach, survival depended on the time to recovery of renal function face to face to progressive exhaustion of available vessels for cannulation. A late recovery precluded survival simply because it became impossible to access the patient’s circulation. Alwall and Norvitt [4] developed an ingenious arteriovenous glass shunt in 1948 but this was marred by major thrombotic problems; the lack of adequate material with limited thrombogenic potential remained an unresolved problem over the subsequent decade. In 1960, Quinton et al. [5] developed the first Teflon shunt allowing long-term vascular access with a reasonably low incidence of clotting episodes. The effectiveness and the safety of this approach was further improved by the use of silicone shunts. In 1962, anticipating the idea of arterio-venous fistula, Cimino proposed a new method allowing repeated dialyses by venipuncture in the arm [6]. In brief, he created intermittent tourniquet pressure in the arm by a sphygmomanometer, applied

During the phased transition from a paper-based record to an electronic health record (EHR), we found that clinicians had difficulty remembering where to find important clinical documents. We describe our experience with the design and use of a web-based map of the hybrid medical record. With between 50 to 75 unique visits per day, the UCare Navigator has served as an important aid to clinicians practicing in the transitional environment of a large EHR implementation.

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This study sought to answer the question: What percentage of an LDS Hospital patient's chart is contained in the HELP system? Using the number of pages in the record as the criteria, the answer is about 26 percent overall, but between 35 percent and 40 percent for patients in nursing divisions where computerized nurse charting is used. Although this fraction is likely to rise in the near future, the critical factor driving computerization is the desire for data usable in computerized decision making rather than the need to computerize the entire chart per se. The medical record at LDS Hospital will probably be a hybrid of computerized and paper data for some time to come.

BACKGROUND/AIMS: As epilepsy is a complex disease group, it is difficult to diagnose and classify. Oxidative stress plays a vital role in the pathogenesis of epilepsy. This study investigated the total oxidant/antioxidant status levels in patients with focal onset and generalized onset seizures. The results we obtained may help find the etiological cause in patients with seizure complaints and may guide their treatment. In addition, knowing the seizure type of the patient can give an idea about the prognosis of their disease.MATERIALS AND METHODS: The total number of patients included in this prospective study was 58. There were also 57 people in a control group. The patients were classified according to their type of seizure: focal or generalized onset. The serum oxidative stress index (OSI) and total oxidant/antioxidant status values of all patients and control group members were measured. The patients (focal/generalized groups) and control group members were compared.RESULTS: This prospective study was completed with 58 eligible patients who met the inclusion criteria. There were 57 people in the control group. Total oxidant status (TOS) and OSI levels were higher in the seizure groups compared to the control group (p

Background: The impact of public health policy to reduce the spread of COVID-19 on access to surgical care is poorly defined. We aim to quantify the surgical backlog during the COVID-19 pandemic in the Brazilian public health system and determine the relationship between state-level policy response and the degree of state-level delays in public surgical care. Methods: Monthly estimates of surgical procedures performed per state from January 2016 to December 2020 were obtained from Brazil's Unified Health System Informatics Department. Forecasting models using historical surgical volume data before March 2020 (first reported COVID-19 case) were constructed to predict expected monthly operations from March through December 2020. Total, emergency, and elective surgical monthly backlogs were calculated by comparing reported volume to forecasted volume. Linear mixed effects models were used to model the relationship between public surgical delivery and two measures of health policy response: the COVID-19 Stringency Index (SI) and the Containment & Health Index (CHI) by state. Findings: Between March and December 2020, the total surgical backlog included 1,119,433 (95% Confidence Interval 762,663–1,523,995) total operations, 161,321 (95%CI 37,468–395,478) emergent operations, and 928,758 (95%CI 675,202–1,208,769) elective operations. Increased SI and CHI scores were associated with reductions in emergent surgical delays but increases in elective surgical backlogs. The maximum government stringency (score = 100) reduced emergency delays to nearly zero but tripled the elective surgical backlog. Interpretation: Strong health policy efforts to contain COVID-19 ensure minimal reductions in delivery of emergent surgery, but dramatically increase elective backlogs. Additional coordinated government efforts will be necessary to specifically address the increased elective backlogs that accompany stringent responses.

Background Control of cutaneous leishmaniasis by public health systems in the Americas relies on case identification and treatment. Point-of-care diagnostics that can be performed by health workers within or near affected communities could effectively bring the health system to the resource-limited sites providing early diagnosis and treatment, reducing morbidity and the burden of disease. Methodology/principal findings A cross-sectional study was undertaken to evaluate the diagnostic test performance of Isothermal Recombinase Polymerase Amplification (RPA) targeting Leishmania kinetoplast DNA, coupled with a lateral flow (LF) immunochromatographic strip, in a field setting and a laboratory reference center. Minimally invasive swab and FTA filter paper samples were obtained by community health workers and highly trained technicians from ulcerated lesions of > 2 weeks’ evolution from 118 patients’ ≥ 2 years of age in the municipality of Tumaco, Nariño. Extracted DNA was processed by RPA-LF at a reference center or in a primary health facility in the field. Evaluation was based on a composite “gold standard” that included microscopy, culture, biopsy and real-time polymerase chain reaction detection of Leishmania 18S rDNA. Standard of care routine diagnostic tests were explored as comparators. Sensitivity and specificity of RPA-LF in the reference lab scenario were 87% (95%CI 74–94) and 86% (95%CI 74–97), respectively. In the field scenario, the sensitivity was 75% (95%CI 65–84) and specificity 89% (95%CI 78–99). Positive likelihood ratios in both scenarios were higher than 6 while negative likelihood ratios ranged to 0.2–0.3 supporting the usefulness of RPA-LF to rule-in and potentially to rule-out infection. Conclusions/significance The low complexity requirements of RPA-LF combined with non-invasive sampling support the feasibility of its utilization by community health workers with the goal of strengthening the diagnostic capacity for cutaneous leishmaniasis in Colombia. Trial registration ClinicalTrials.gov NCT04500873., Author summary Limited access to diagnosis is a critical determinant of the “neglect” that defines the so-called Neglected Tropical Diseases (NTDs) including cutaneous leishmaniasis. Diagnostic tests that can be performed close to and involve the participation of the affected communities would improve access to treatment as well as diagnosis. Using non-invasive swab and filter paper samples obtained by Community Health Workers, we evaluated the diagnostic performance of an innovative and technically simple molecular test: Isothermal Recombinase Polymerase Amplification (RPA) to detect Leishmania DNA, coupled with a lateral flow (LF) strip to read the results with the naked eye. The RPA-LF test demonstrated high sensitivity and specificity and capacity to rule in or rule out a diagnosis of cutaneous leishmaniasis in both an endemic field setting and reference laboratory. The findings encourage the further optimization of the test format for Point-of-Care diagnosis by health personnel and rural health workers in endemic settings.

In most low-resource settings, microscopy still is the standard method for diagnosis of cutaneous leishmaniasis, despite its limited sensitivity. In Ethiopia, the more sensitive molecular methods are not yet routinely used. This study compared five PCR methods with microscopy on two sample types collected from patients with a suspected lesion to advise on optimal diagnosis of Leishmania aethiopica. Between May and July 2018, skin scrapings (SS) and blood exudate from the lesion spotted on filter paper (dry blood spot, DBS) were collected for PCR from 111 patients of four zones in Southern Ethiopia. DNA and RNA were simultaneously extracted from both sample types. DNA was evaluated by a conventional PCR targeting ITS-1 and three probe-based real-time PCRs: one targeting the SSU 18S rRNA and two targeting the kDNA minicircle sequence (the ‘Mary kDNA PCR’ and a newly designed ‘LC kDNA PCR’ for improved L. aethiopica detection). RNAs were tested with a SYBR Green-based RT-PCR targeting spliced leader (SL) RNA. Giemsa-stained SS smears were examined by microscopy. Of the 111 SS, 100 were positive with at least two methods. Sensitivity of microscopy, ITS PCR, SSU PCR, Mary kDNA PCR, LC kDNA PCR and SL RNA PCR were respectively 52%, 22%, 64%, 99%, 100% and 94%. Microscopy-based parasite load correlated well with real-time PCR Ct-values. Despite suboptimal sample storage for RNA detection, the SL RNA PCR resulted in congruent results with low Ct-values. DBS collected from the same lesion showed lower PCR positivity rates compared to SS. The kDNA PCRs showed excellent performance for diagnosis of L. aethiopica on SS. Lower-cost SL RNA detection can be a complementary high-throughput tool. DBS can be used for PCR in case microscopy is negative, the SS sample can be sent to the referral health facility where kDNA PCR method is available., Author summary Cutaneous leishmaniasis is a neglected tropical disease and causing a public health problem in Ethiopia. Microscopy is still the standard method for detection of the parasite in Ethiopia, and also in many other low resource settings. A more sensitive method is needed for timely diagnosis and treatment. In this study, we compared five molecular methods on samples collected from patients with a skin lesion suspected of cutaneous leishmaniasis to advice on optimal diagnosis of L. aethiopica. We collected two sample types from the same lesion (skin scrapings and lesion fluid on filter paper) and isolated both DNA and RNA of them. Majority (90.1%) of the samples from skin scrapings were positive in two or more methods and the molecular methods had a higher sensitivity than the conventional methods. Interestingly, we evaluated for the first time a new molecular method designed to improve L. aethiopica detection. Also, we showed that RNA detection performed well for samples that were collected under difficult field conditions. Samples collected on filter paper showed less positive results than skin scraped samples, but could still be the method of choice for easy sampling and transport in resource-limited settings as it performed better than microscopy.

The impact of left bundle branch block (LBBB) related mechanical dyssynchrony on left ventricular (LV) diastolic function remains unclear. 4D flow cardiovascular magnetic resonance (CMR) has provided reliable markers of LV dysfunction: reduced volume and kinetic energy (KE) of the portion of LV inflow which passes directly to outflow (Direct Flow) has been demonstrated in failing hearts compared to normal hearts. We sought to investigate the impact of mechanical dyssynchrony on diastolic function by comparing 4D flow in myopathic LVs with and without LBBB. CMR data were acquired at 3 T in 22 heart failure patients; 11 with LBBB and 11 without LBBB matched according to several demographic and clinical parameters. An established 4D flow analysis method was used to separate the LV end-diastolic (ED) volume into functional flow components based on the blood’s timing and route through the heart cavities. While the Direct Flow volume was not different between the groups, the KE possessed at ED was lower in LBBB patients (P = 0.018). Direct Flow entering the LV during early diastolic filling possessed less KE at ED in LBBB patients compared to non-LBBB patients, whereas no intergroup difference was observed during late filling. Pre-systolic KE of LV Direct Flow was reduced in patients with LBBB compared to matched patients with normal conduction. These intriguing findings propose that 4D flow specific measures can serve as markers of LV mechanical dyssynchrony in heart failure patients, and could possibly be investigated as predictors of response to cardiac resynchronization therapy. Electronic supplementary material The online version of this article (doi:10.1007/s10554-017-1261-5) contains supplementary material, which is available to authorized users.

Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of 3 functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls. Subjects were genotyped regarding the mu-opioid receptor (OPRM1) gene (rs1799971), the serotonin transporter (5-HTT) gene (5-HTTLPR/rs25531), and the serotonin-1a receptor (5-HT1a) gene (rs6296). The patients with FM had increased pain sensitivity and reduced EIH compared with healthy controls. None of the polymorphisms had an effect on EIH on their own. We found significant gene-to-gene interactions between OPRM1 x 5-HTT and OPRM1 x 5-HT1a regarding activation of EIH, with no statistically significant difference between groups. Better EIH was found in individuals with genetically inferred strong endogenous opioid signaling (OPRM1 G) in combination with weak 5-HT tone (5-HTT low/5-HT1a G), compared with strong 5-HT tone (5-HTT high/5-HT1a CC). Based on the proposed mechanisms of these genetic variants, the findings indicate antagonistic interactions between opioid and serotonergic mechanisms during EIH. Moreover, despite different baseline pain level, similar results were detected in FM and controls, not supporting an altered interaction between opioid and 5-HT mechanisms as the basis for dysfunction of EIH in patients with FM. In summary, our results suggest that, by genetic association, the mu-opioid receptor interacts with 2 major serotonergic structures involved in 5-HT reuptake and release, to modulate EIH.

Nano-enabled technologies hold great promise for medicine and health. The rapid progress by the physical sciences/engineering communities in synthesizing nanostructures and characterizing their properties must be rapidly exploited in medicine and health toward reducing mortality rate, morbidity an illness imposes on a patient, disease prevalence, and general societal burden. A National Science Foundation–funded workshop, “Re-Engineering Basic and Clinical Research to Catalyze Translational Nanoscience,” was held 16–19 March 2008 at the University of Southern California. Based on that workshop and literature review, this article briefly explores scientific, economic, and societal drivers for nanomedicine initiatives; examines the science, engineering, and medical research needs; succinctly reviews the US federal investment directly germane to medicine and health, with brief mention of the European Union (EU) effort; and presents recommendations to accelerate the translation of nano-enabled technologies from laboratory discovery into clinical practice. From the Clinical Editor An excellent review paper based on the NSF funded workshop “Re-Engineering Basic and Clinical Research to Catalyze Translational Nanoscience” (16-19 March 2008) and extensive literature search, this paper briefly explores the current state and future perspectives of nanomedicine.

Epigenetic silencing of tumor suppressor genes (TSGs) by promoter methylation can be an early event in the multi-step process of carcinogenesis. Human chromosome 3 contains clusters of TSGs involved in many cancer types including nasopharyngeal carcinoma (NPC), the most common cancer in Southern China. Among ten candidate TSGs identified in chromosome 3 using NotI microarray, ITGA9 and WNT7A could be validated. 5-aza-2 deoxycytidine treatment restored the expression of ITGA9 and WNT7A in two NPC cell lines. Immunostaining showed strong expression of these genes in the membrane and cytoplasm of adjacent control nasopharyngeal epithelium cells, while they were weakly expressed in NPC tumor cells. The ITGA9 promoter showed marked differentially methylation between tumor and control tissue, whereas no differentially methylation could be detected for the WNT7A promoter. The expression level of ITGA9 in NPC tumors was downregulated 4.9-fold, compared to the expression in control. ITGA9 methylation was detected by methylation specific PCR (MSP) in 56% of EBV positive NPC-cases with 100% specificity. Taken together, this suggests that ITGA9 might be a TSG in NPC that is involved in tumor cell biology. The possibility of using ITGA9 methylation as a marker for early detection of NPC should further be explored. Funding Agencies|Cancerfonden; Cancerforeningen in Stockholm; National Natural Science Foundation of China [81202135]; Project for the Development of University of Balochistan, Quetta, Pakistan

The recent revision of ISO15189 has further strengthened its position as the standard for accreditation for medical laboratories. Both for laboratories and their customers it is important that the scope of such accreditation is clear. Therefore the European co-operation for accreditation (EA) demands that the national bodies responsible for accreditation describe the scope of every laboratory accreditation in a way that leaves no room for doubt about the range of competence of the particular laboratories. According to EA recommendations scopes may be fixed, mentioning every single test that is part of the accreditation, or flexible, mentioning all combinations of medical field, examination type and materials for which the laboratory is competent. Up to now national accreditation bodies perpetuate use of fixed scopes, partly by inertia, partly out of fear that a too flexible scope may lead to over-valuation of the competence of laboratories, most countries only use fixed scopes. The EA however promotes use of flexible scopes, since this allows for more readily innovation, which contributes to quality in laboratory medicine. In this position paper, the Working Group Accreditation and ISO/CEN Standards belonging to the Quality and Regulation Committee of the EFLM recommends using an approach that has led to successful introduction of the flexible scope for ISO15189 accreditation as intended in EA-4/17 in The Netherlands. The approach is risk-based, discipline and competence-based, and focuses on defining a uniform terminology transferable across the borders of scientific disciplines, laboratories and countries.

Introduction: Acute intoxications with corrosive substances can cause severe chemical injuries of the upper gastrointestinal tract, most often located in the mouth, pharynx, esophagus, stomach and duodenum. If a patient survives the acute phase of intoxication, regenerative response may result in esophageal and/or gastric stenosis, and increased risk of esophageal and gastric cancer. Such intoxication may be fatal due to perforation or tracheal necrosis. Enteral nutrition is a nutritional method when nutritional substances are administered through specially designed tubing placed through the nose or percutaneously, directly into the GIT. Aim: The aim of this study is to describe the methods of artificial nutrition in patients with acute corrosive intoxications and the importance of nutritional support in the treatment of these intoxications. Discussion: Nutrition in the treatment of acute corrosive intoxications is one of the most important therapeutic processes that largely contribute to faster recovery of the post-corrosive injuries of upper GIT, stabilization of biologic, immunologic and metabolic parameters, and reduction of length of stay in hospital Aim of the treatment of acute corrosive intoxications is to prevent perforation and progressive fibrosis, and esophageal and gastric stenosis. There are different and often conflicting positions, on the conservative treatment of acute corrosive intoxications in adults. Such treatment mainly consists of anti-secretory treatment, antibiotics and intensive hyper-alimentation, aiming to prevent late post-corrosive intoxications. Conclusion: It is considered that nutritional support plays a major role in maintenance of metabolic processes and prevention of severe metabolic complications that could additionally aggravate the condition and impair the treatment. Key words: corrosive poisonings, deglutition, deglutition disorders, nutritional therapy, enteral nutrition, parenteral nutrition

SUMMARYInfluenza causes severe illness and deaths, and global surveillance systems use different clinical case definitions to identify patients for diagnostic testing. We used data collected during January 2007–July 2010 at hospital-based influenza surveillance sites in western Kenya to calculate sensitivity, specificity, positive predictive value, and negative predictive value for eight clinical sign/symptom combinations in hospitalized patients with acute respiratory illnesses, including severe acute respiratory illness (SARI) (persons aged 2–59 months: cough or difficulty breathing with an elevated respiratory rate or a danger sign; persons aged ⩾5 years: temperature ⩾38 °C, difficulty breathing, and cough or sore throat) and influenza-like illness (ILI) (all ages: temperature ⩾38 °C and cough or sore throat). Overall, 4800 persons aged ⩾2 months were tested for influenza; 416 (9%) had laboratory-confirmed influenza infections. The symptom combination of cough with fever (subjective or measured ⩾38 °C) had high sensitivity [87·0%, 95% confidence interval (CI) 83·3–88·9], and ILI had high specificity (70·0%, 95% CI 68·6–71·3). The case definition combining cough and any fever is a simple, sensitive case definition for influenza in hospitalized persons of all age groups, whereas the ILI case definition is the most specific. The SARI case definition did not maximize sensitivity or specificity.

Background: Bone lytic lesion in Multiple myeloma are the most commonly presented symptoms which require treatment with bisphosphonates (BPs). BPs are providing supportive care, reducing the rate of skeletal morbidity but evidently not abolishing it, the criteria for stopping their administration have to be different from those used for classic antineoplastic drugs, and they should not be stopped when metastatic bone disease is progressing. Osteonecrosis of the jaw (ONJ) has been associated recently with the use of BPs. Aim: The aim of these study is to evaluate the incidence of ONJ in patients with MM treated with mixed biphosphonates. Patients and methods: We analyzed total 296 myeloma patients (150 male and 146 female). Mostly effected age group with 58,1% is age more than 60 years up to 88 years, diagnosed in our institution in the period 2005-2015. We used intravenous or oral forms of biphosphonates such as pamidronate, ibandronate, clodronate and zolendronic acid. The patients were evaluated for ONJ. Results: The incidence of ONJ in our group of patients treated with Bps was 4,6% from our group of 260 patients 87,8% received BPs therapy and patients which haven’t received BPs 12,2%. From this group, 95,4% (248) didn’t show ONJ, and 4,6% (12) showed ONJ. The period of this treatment with BPs is an important risk factor for development of ONJ, average duration of BPs therapy in patients which show adverse effects is 26.8±13.7 months, from the total number of 12 patients that developed ONJ adverse effects, we have 8 patients which received treatment with Zolendronic acid and the remaining 4 patients which were treated with other BPs combinations without Zolendronic acid. Conclusions: All patients treated for MM must continue with the therapy with Zolendronic acid and Pamidronate, each patient must be individually treated according to his response of the treatment (dose, frequency and duration of therapy).

In contrast to public health and the resolution to further increase the health care of the whole community in regions worldwide, current clinical medicine has its limits. Further improvement in public health - rather than individual diseases - can only be achieved by integrating new views into treatment. Some years ago, the concept of biopsychosocial medicine was integrated into patient treatment and is now generally accepted. Therefore the author describes here a new dimension to treatment and presents substantial evidence to include ecological health in this already existing concept. The problem of community education is discussed.

Objective: To determine the effectiveness of providing synthesized research evidence to inform patient care practices via an evidence based informatics program, the Clinical Informatics Consult Service (CICS). Design: Consults were randomly assigned to one of two conditions: CICS Provided, in which clinicians received synthesized information from the biomedical literature addressing the consult question or No CICS Provided, in which no information was provided. Measurement: Outcomes were measured via online post-consult forms that assessed consult purpose, actual and potential impact, satisfaction, time spent searching, and other variables. Results: Two hundred twenty six consults were made during the 19-month study period. Clinicians primarily made requests in order to update themselves (65.0%, 147/226) and were satisfied with the service results (Mean 4.52 of possible 5.0, SD 0.94). Intention to treat (ITT) analyses showed that consults in the CICS Provided condition had a greater actual and potential impact on clinical actions and clinician satisfaction than No CICS consults. Evidence provided by the service primarily impacted the use of a new or different treatment (OR 8.19 95% CI 1.04–64.00). Reasons for no or little impact included a lack of evidence addressing the issue or that the clinician was already implementing the practices indicated by the evidence. Conclusions: Clinical decision-making, particularly regarding treatment issues, was statistically significantly impacted by the service. Programs such as the CICS may provide an effective tool for facilitating the integration of research evidence into the management of complex patient care and may foster clinicians' engagement with the biomedical literature.

Extracellular circulating microRNAs (miRNAs) have been suggested to be biomarkers for disease monitoring but data are inconsistent, one reason being that blood miRNA is of heterogeneous origin. Here, we sampled extracellular microRNAs locally in situ using microdialysis. Three different cohorts of women were included; postmenopausal women with ongoing breast cancer investigated within the cancer and in normal adjacent breast tissue, postmenopausal women investigated in their normal healthy breast and subcutaneous fat before and after six weeks of tamoxifen therapy, premenopausal women during the menstrual cycle. Samples were initially screened using TaqMan array cards with subsequently absolute quantification. 124 miRNA were expressed in microdialysates. After absolute quantifications extracellular miRNA-21 was found to be significantly increased in breast cancer. In addition, the levels were significantly higher in pre-menopausal breast tissue compared with postmenopausal. In breast tissue of pre-menopausal women miRNA-21 exhibited a cyclic variation during the menstrual cycle and in postmenopausal women six weeks of tamoxifen treatment decreased miRNA-21 suggesting that this miRNA may be important for breast carcinogenesis. None of these changes were found in plasma or microdialysates from subcutaneous fat. Our data revealed tissue specific changes of extracellular circulating miRNAs that would be otherwise unraveled using blood samples. Funding Agencies|Swedish Cancer Society [2012/454]; Swedish Research Council [2013-2457]; Linkoping University

Writing in Medical Education in 1982, Fowkes (1982) noted the lack of general agreement within the medical profession on methods of audit, a deficiency previously articulated by Shaw (1980) and later emphasized by McIntyre (1985). More recently, a study by Black & Thompson (1993) of consultant and junior medical staff in four London district general hospitals revealed that ‘many doctors did not understand how to undertake audit’, and major research by both Hopkins (1993, 1994) and Buttery et al. (1994) described a multiplicity of methodological deficiencies in the general approaches to audit adopted by clinicians since the promulgation of the White Paper definition in 1989. Soundness of methodological approach is fundamental to securing the success of clinical audit within Provider organizations and is thus central to the generation of measurable improvements in the quality of clinical care being delivered to patients. It is therefore disturbing that methodological deficiencies may still be observed in general approaches to audit (Buttery et al. 1994), with no author yet recommending a formal system for critical inquiry into clinical practice. It was the recognition of the unsatisfactory nature of this situation which led us to develop a system aimed at assessing, in a critical fashion, the quality of the totality of care dispensed within NHS provider organizations. The system is presented here for the first time.

Objective To estimate the coverage provided by SNOMED CT for clinical research concepts represented by the items on case report forms (CRFs), as well as the semantic nature of those concepts relevant to post-coordination methods. Design Convenience samples from CRFs developed by rheumatologists conducting several longitudinal, observational studies of vasculitis were selected. A total of 17 CRFs were used as the basis of analysis for this study, from which a total set of 616 (unique) items were identified. Each unique data item was classified as either a clinical finding or procedure. The items were coded by the presence and nature of SNOMED CT coverage and classified into semantic types by 2 coders. Measurements Basic frequency analysis was conducted to determine levels of coverage provided by SNOMED CT. Estimates of coverage by various semantic characterizations were estimated. Results Most of the core clinical concepts (88%) from these clinical research data items were covered by SNOMED CT; however, far fewer of the concepts were fully covered (that is, where all aspects of the CRF item could be represented completely without post-coordination; 23%). In addition, a large majority of the concepts (83%) required post-coordination, either to clarify context (e.g., time) or to better capture complex clinical concepts (e.g., disease-related findings). For just over one third of the sampled CRF data items, both types of post-coordination were necessary to fully represent the meaning of the item. Conclusion SNOMED CT appears well-suited for representing a variety of clinical concepts, yet is less suited for representing the full amount of information collected on CRFs.

As I write this JMT update, it seems like yesterday that the Internet Journal of Medical Toxicology (IJMT) was transitioning to the Journal of Medical Toxicology (JMT). Can it really be time for volume 10? When one is entrenched in the details, it is easy to forget the big picture. The big picture for JMT continues to be bright. There has been quite a bit of activity for JMT in 2013, sustained in large part by the invaluable efforts of our editorial board and reviewers. The editorial board continues to evolve, with three board members, Russ Kerns, Stephen Borron, and Ed Boyer, rotating off after productive terms. Our two fellow-in-training members, Patrick Lank and Aaron Skolnik, graduated in 2013 and two incoming fellows, Navneet Cheema and Mark Neavyn, joined the board. Navneet has been instrumental, with Nathanael McKeown, at updating the JMT portion of the American College of Medical Toxicology (ACMT) website, adding extensive instructions for author section, as well as links to articles available online, podcasts, all of the journals policies, and more. Mark is organizing the online issues of IJMT to make them accessible to members. Mark Mycyk writes a press release for every print issue of JMT, increasing our media presence, and the JMT Facebook page has been much more active with more “likes” weekly. Our ACMT tweeter, Joseph D'Orazio, also includes us in his prolific activity. The entertaining and informative podcasts for each print issue continue to be produced by Dan Rusyniak and Howard Greller. Thanks to the efforts of Chuck McKay and Lynn Lancaster, the December issue included the proceedings from the ACMT symposium on chelation. The Toxicology Investigators Consortium report also appeared in the December issue, the third annual report published in JMT by this group. JMT is partnering with the CDC to offer continuing medical education (CME) for reviewers. The application was approved this fall, and reviewers will be able to collect physician and pharmacy CME for reviews performed. Rick Wang was instrumental in shepherding this innovative project to completion. Thanks to the efforts of Lewis Nelson, JMT was able to copublish the National Association of Medical Examiners Position Paper: Recommendations for the Investigation, Diagnosis, and Certification of Deaths Related to Opioid Drugs. We also published a joint position statement with AACT on Antidote Shortages in the US, developed with the oversight of Silas Smith. Article submissions more than tripled from 2007 to 2013, and rejection rate increased to 50 %. Submissions came from over 47 countries across various regions including North America, Europe, Asia, and the Middle East. The number of submissions continues to increase steadily. Full-text article downloads are also increasing steadily from 1 year to the next, including a significant increase of 56 % from 2011 to 2012. As of early August 2013, a Scopus search indicated the following: Journal of Medical Toxicology: 199 citations year-to-date 2013, to 159 articles published in 2011 + 2012 = 1.25 average citations per article. While this does not equate exactly with impact factor, it suggests that our articles are being cited. With this promising data and the help of Springer, JMT has applied for an impact factor. It can take a considerable amount of time (years) to get a decision, but we are optimistic. The editorial board has been tirelessly working toward this important goal. Finally, I attended the International Congress of Peer Review in Chicago in September 2013. The event only occurs every 4 years. Christine Murphy, a member of the editorial board, also attended. It was a fascinating opportunity to meet some of the big names in medical publishing and hear them speak. It was also interesting to discuss the latest research in peer review, including the controversy about open access and conflicts of interest. While much has been done in this area, there are many opportunities for further research. As we approach our tenth year, I extend my appreciation to all of the editorial staff, reviewers, and editorial board members, as well as the previous editors. I also want to thank ACMT for its incredible support of this important endeavor.

Introduction: Myeloma multiplex is defined by the presence of monoclonal plasma cell population in the bone marrow>10%,M protein in the serum and/or urine ,and clinical evidence of end organ damage like hypercalcemia ,renal failure, anemia, or bone lesions. In the most hematologic malignancies the role of induction treatment is to achieve complete remission (CR). Thalidomide became a new therapeutic approach but use of Thalidomide as a single agent or combination with steroids or chemotherapy is associated with several side effects like deep vein thrombosis (DVT), peripheral neuropathy (PN), constipation, somnolence, pyrexia, pain, fatigue osteonecrosis of jaw, and teratogenicity that is the most worrying adverse event. Risk of appearance of DVT increased if we use combination of Thalidomide plus Dexamethasone plus cytotoxic chemotherapy such Cyclophosphamide. >30% DVT usually occurs during the first months of treatment and is more frequent in newly diagnosed patients with a high tumor burden. The second side effect is peripheral neuropathy (PN) which occurs in 50% of patients with MM treated with Thalidomide plus Dexamethasone and chemotherapy. Patients and methods: Eighty patients of both sexes (43 males and 37 females) at the age of 31-81 (median range 58 years) with MM, were treated–one group with combinations of Thalidomide plus Dexamethasone plus Cyclophosphamide (CyThalDex) 4 cycle(>4months), and the other group with Thalidomide plus Dexamethasone plus Melphalan (MPT), (>4month) and third group with high dose of chemotherapy and continue with ThalDex (TD), the fourth group with CyThalDex, > than 5 cycles, and the fifth group with ThalDex (TD) only. Results: It is obvious while myelo-suppression is very rare, the incidence of nonhematologic side effects is high and dose dependent. Eight (or 10%) patients that developed DVT and CVI were initially treated with antiaggregation therapy of Aspirin 100mg per day, but those that already developed were treated with low dose of Heparin 40000 iE per day in ten days and continued with oral anticoagulans therapy. However, besides the given therapy in four (or 5 %) patients there was exitus letalis. PN was developed in twentyone patients (or 26.25%) from the total number of patients treated with Thalidomide, in ten patients the dosage of Thalidomide was decreased to 50mg per day, in one patient with Epi attacks it was interrupted and the other was with paresis n.occulomotorius and n.abducens. Conclusions: Patients treated with thalidomide have an increased risk of arterial thromboembolism, including myocardial infarction and cerebrovascular events, in addition to the established risk of venous thromboembolism, but most patients who presenting DVT or some of thromboembolic events have had identifiable risk factors. The prolonged exposure to Thalidomide seems to induce resistance of MM reducing overall survival (OS). We must evaluate consolidation and maintenance therapies with Thalidomide, determinate which regimens provide a highness benefit with favorable side effect profiles in specific subgroups of patients.

Medicine is traditionally known as an 'art', and not an exact 'science'. Medical images of clinical signs and pathology were communicated through 'metaphors' in the 19th and early 20th centuries to make recognition easier in anticipation of the clinical counterpart when encountered in medical practice. They have served as teaching aids, enhancing memory retention for medical students, nurses and doctors and have withstood the test of time. Standard medical textbooks contain metaphors that have become entrenched in teaching, learning and examining in medical schools and hospitals worldwide. The continued use of metaphors has given rise to an ongoing debate, particularly in Africa, due to the usage of inappropriate or unfamiliar metaphors which are not locally or culturally relevant. Despite this, medical analogies will no doubt continue to be useful for medical education, clinical practice and 'aide memoirs' for examinations, and bring light humour, for a long time to come.

INTRODUCTION: Acute corrosive poisonings are caused by ingestion of corrosive chemicals which are most commonly used as household agents. Intoxications with these kind of agents produce numerous and severe post-corrosive complications of the upper gastrointestinal tract. On the other hand, our experience showed that corrosive agents may also cause injuries of the respiratory system, which makes the treatment very hard and additionally complicates the severe clinical condition of the patient. OBJECTIVE: The aim of the study is to show the incidence of respiratory complications in acute corrosive poisonings, the need of various clinical investigations and also the treatment and final outcome of these kind of poisoning. METHODS: We retrospectively analyzed clinical records of 415 patients hospitalized and treated at the University clinic for toxicology and urgent internal medicine, in Skopje, Republic of Macedonia, in the period between 2007 and 2011. The protocol consisted of methods for analyzing the systemic complications, with an accent on the post-corrosive respiratory complications. RESULTS: From the total number of patients even 98 (23.61%) exhibited systemic complications, from which 51 (52.04%) are respiratory complications. The majority of patients are female (n=40, 78.43%) and the most common complication is pneumonia (n=47). The youngest patient in this study was 14 and the oldest was 87 years old. CONCLUSION: Besides the gastrointestinal complications in the acute corrosive poisonings respiratory complications are also very often. They complicate the clinical state of patient and very often lead to fatal endings. Language: en

The extraordinary increase in life-expectancy that occurred early in this century has been attributed largely to non-medical factors. Life-expectancy has continued to rise, and medical care can now be shown to make substantial contributions. Three of the seven years' increase in life expectancy since 1950 can be attributed to medical care. Medical care is also estimated to provide, on average, five years of partial or complete relief from the poor quality of life associated with chronic disease. The association of social factors with health is well-known, but except for occupation, it is not known how they might act or whether they are proxies for some other yet to be identified factor.

Infantile hemangiomas are oneof the most common benign vascular tumors in infants and children. Because hemangiomas can resolve spontaneously, they usually do not require specific treatment unless the proliferation interferes with normal function or causes interference with the function of essential vital organs. There are severaltypes of therapy, but in recent decades the use of propranolol has become more common due to its excellent effectiveness. The purpose of this paper is to analyze different pharmaceutical formulations of propranolol in the treatment of infantile hemangioma, including technological differences of the oral and topical pharmaceutical dosage forms of propranolol. The European Medicines Agency (EMA) has approved the commercially available oral propranolol therapy in the countries of the European Union, but thisis not yet happened in our country. Recommendations to follow and use the protocols for the oral application of propranolol in the treatment of this disease are difficult due to the fact that this drug formulation is not registered in our country and patients are forced to obtain it from countries where it is registered. The use of syrup as an oral form of therapy has been clinically proven and has a high percentage of efficiency in infantile hemangioma, but side effectssuch as sleep disturbance, bronchospasm, hypoglycemia, hypotension. The goal of this publication is to propose the most appropriate topical formulation of propranolol for external use in infantile hemangioma through a review of relevant published data on the use of various pharmaceutical formulations of propranolol in clinical studies and documents from the European Medicines Agency,In this paper, we used compilation and comparison methods, as most useful for a high-quality critical evaluation of the literature regarding problematic topics, in our case the pharmaceutical formulation of propranolol, the effect of clinical treatment and the required legislation, and which have the potential to promote clearer, shared understandings and accelerate advances in the research. Our results were focused on obtained and published data related to pharmaceutical-technological aspects of production of topical formulations and the effect of clinical application, especially when it is necessary to define exactly the amount of the released active compoundfrom the topical form (cream, ointment or gel) and its absorption through the skin.Topical form of propranolol avoids the side effects of oral administrated propranolol, can help maintain a high level of active ingredient in a local or focal region, and has an easy way of administration.The obtained research data showed that the topical application and penetration of propranolol through the skin is good and has a lower and controlled systemic absorption. To achieve this, the choice of the formulation andthe excipients used are particularly important. Lipophilic formulations have limited release and penetration of propranolol. The best results are achieved by using a hydrophilic cream.After the research done, we can conclude that the production of topical formulations containing specific active components with a strong systemic effect, such as propranolol, can be carried out in galenic laboratories or hospital pharmacies. For this, already existing validated equipment and excipients that are readily available can be used. We believe that the use of topical pharmaceutical forms for local application, even in children such as the case of propranolol in infantile hemangioma, is justified, especially to the fact that so far no side effects have been registered even after long-term therapy

Two wheeled Self balancing robots have become more popular in recent times and used in many applications, commonly used in transportation as these balancing robots are faster and apparently stable. Balancing is achieved by using controllers tuned for the system. Inverted pendulum principle is used in these robots. This paper proposes the use of two control methods, namely Proportional-Integral-Derivative (PID) and Extended PID (EPID), for maintaining the balance of two-wheeled and self-balancing robots, even when slightly tilted, thus preventing them from falling. PID control theory generally depends up on transfer functions, this paper extends the theory using EPID. EPID provides a new perspective on the working principle of PID control and its relationship with other control theories, such as tracking control and disturbance observer. This approach is illustrated using the fundamental principle of inverted pendulum technology. The key advantage of these robots over other mobile robots is their increased stability due to zero turning radius, which allows for smoother rotations during changes in direction.

Removal of impacted permanent third molars is considered to be one of the most common and routine oral surgical procedures. This intervention is usually performed in the classical way with the use of rotatory instruments and burs. As an alternative to this classical approach, piezosurgery can be used, which is an osteotomy technique based on ultrasonic vibrations. The crucial advantage of piezosurgery is that it is inert to soft tissues. The aim of this study was to compare piezosurgery with the rotatory osteotomy technique, with particular reference to the time required to perform the intervention and the intensity of postoperative sequelae: pain, swelling, and trismus. This paper summarizes published experiences and knowledge of piezosurgery, with special regard to the extraction of mandibular third molars. For the purposes of this research, an automatic detailed search was performed on the electronic database PubMed for the period 2012-2022. Keywords used in the search were: piezosurgery, impacted third molars. The initial filtration resulted in 47 scientific papers, 17 of which met the selection criteria. Of particular interest were papers such as Meta-analyzes and systematic reviews. A review of the literature indicates that although patients undergoing piezosurgery required longer operating times, they had less postoperative pain, swelling, and trismus. Keywords: impacted molar, piezosurgery.

PurposeWhen the augmentative and alternative communication (ACC) model (Lloyd et al., 1990) was proposed, these components of symbols were not considered, nor were they contemplated when superordinate (Lloyd and Fuller, 1986) and subordinate levels (Fuller et al., 1992) of AAC symbol taxonomy were developed. The purpose of this paper is to revisit the ACC model and propose a new symbol classification system called multidimensional quaternary symbol continuum (MQSC)Design/methodology/approachThe field of AAC is evolving at a rapid rate in terms of its clinical, social, research and theoretical underpinnings. Advances in assessment and intervention methods, technology and social issues are all responsible to some degree for the significant changes that have occurred in the field of AAC over the last 30 years. For example, the number of aided symbol collections has increased almost exponentially over the past couple of decades. The proliferation of such a large variety of symbol collections represents a wide range of design attributes, physical attributes and linguistic characteristics for aided symbols and design attributes and linguistic characteristics for unaided symbols.FindingsTherefore, it may be time to revisit the AAC model and more specifically, one of its transmission processes referred to as the means to represent.Originality/valueThe focus of this theoretical paper then, is on the current classification of symbols, issues with respect to the current classification of symbols in terms of ambiguity of terminology and the evolution of symbols, and a proposal for a new means of classifying the means to represent.Peer reviewThe peer review history for this article is available at: https://publons.com/publon10.1108/JET-04-2021-0024

Objective: The proliferation and growing demands of genetic testing are anticipated to revolutionise medical practice. As gatekeepers of healthcare systems, general practitioners (GPs) are expected to play a critical role in the provision of clinical genetic services. This paper aims to review existing literature on GPs' experience, attitudes and needs towards clinical genetic services. Design: A systematic mixed studies review of papers published between 2010 and 2022. Eligibility criteria: The inclusion criterion was peer-reviewed articles in English and related to GPs' experience, views and needs on any genetic testing. Information sources: The PubMed, PsycINFO, Cochrane, EMBASE databases were searched using Mesh terms, Boolean and wildcards combinations to identify peer-reviewed articles published from 2010 to 2022. Study quality was assessed using Mixed Methods Appraisal Tool. Only articles that fulfilled the inclusion criteria were selected. A thematic meta-synthesis was conducted on the final sample of selected articles to identify key themes. Results: A total of 62 articles were included in the review. Uncertainty over GPs' role in providing genetic services were attributed by the lack of confidence and time constraints and rarity of cases may further exacerbate their reluctance to shoulder an expanded role in clinical genetics. Although educational interventions were found to increasing GPs' knowledge and confidence to carry out genetic tasks, varied interest on genetic testing and preference for a shared care model with other genetic health professionals have resulted in minimal translation to clinical adoption. Conclusion: This review highlights the need for deeper exploration of GPs' varied experience and attitudes towards clinical genetic services to better facilitate targeted intervention in the adoption of clinical genetics. Ministry of Health (MOH) Nanyang Technological University National Medical Research Council (NMRC) Published version This research is supported by the Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist Award (MOH-¬000654) as well as the Centre for Primary Health Care Research & Innovation, Lee Kong Chian School of Medicine Seedcorn grant (L0483103 NHG--CPHCRI).

Biosocial Medicine, with its emphasis on the full integration of the person's biology and biography, proposes a strategy for clinical research and the practice of medicine that is transformative for the care of individual patients. In this paper, we argue that Biology is one component of what makes a person unique, but it does not do so alone. Biography, the lived experience of the person, integrates with biology to create a unique signature for each individual and is the foundational concept on which Biosocial Medicine is based. Biosocial Medicine starts with the premise that the individual patient is the focus of clinical care, and that average results for “ideal” patients in population level research cannot substitute for the “real” patient for whom clinical decisions are needed. The paper begins with a description of the case-based method of clinical reasoning, considers the strengths and limitations of Randomized Controlled Trials and Evidence Based Medicine, reviews the increasing focus on precision medicine and then explores the neglected role of biography as part of a new approach to the tailored care of patients. After a review of the analytical challenges in Biosocial Medicine, the paper concludes by linking the physician's commitment to understanding the patient's biography as a critical element in developing trust with the patient.

Purpose Recently published papers have demonstrated that particularly in untreated individuals, clinical parameters more often associate with thyroid hormone, particularly free thyroxine (FT4), levels than with thyrotropin (TSH) levels. Clinical and research assessments of the thyroid state of peripheral tissues would therefore be more precise if they were based on FT4 levels rather than on TSH levels. In this paper we describe implications of, and opportunities provided by, this discovery. Conclusions The FT4 level may be the best single test of thyroid function. The addition of free triiodothyronine (FT3) and TSH levels would further enhance test sensitivity and distinguish primary from secondary thyroid dysfunction respectively. There are opportunities to reconsider testing algorithms. Additional potential thyroidology research subjects include the peripheral differences between circulating FT4 and FT3 action, and outcomes in patients on thyroid replacement therapy in terms of thyroid hormone levels. Previously performed negative studies of therapy for subclinical thyroid dysfunction could be repeated using thyroid hormone levels rather than TSH levels for subject selection and the monitoring of treatment. Studies of outcomes in older individuals with treatment of high normal FT4 levels, and pregnant women with borderline high or low FT4 levels would appear to be the most likely to show positive results. There are fresh indications to critically re-analyse the physiological rationale for the current preference for TSH levels in the assessment of the thyroid state of the peripheral tissues. There may be opportunities to apply these research principles to analogous parameters in other endocrine systems.

Objective The study objective was to enhance clinical skills among undergraduate students majoring in clinical medicine in performing physical examination by establishing a novel platform for peer assessment of clinical skills. Methods A total 126 Year 2012 students majoring in medicine and receiving traditional training were assigned to the control group, and 126 Year 2013 students receiving instruction via the peer assessment platform of clinical skills were allocated to the study group. Scores of the physical examination, paper exam, and peer assessment were compared using a t-test, and we performed linear correlation analysis of the data. Results Scores of the physical examination and peer assessment among Year 2013 students (the study group) were significantly higher than those in the control group. Paper exam scores in the study group were also significantly higher than those in the controls. The three assessment scores did not differ significantly according to sex. Conclusions The peer assessment platform can not only improve medical students’ skills and capabilities in physical examination, it can also enhance their theoretical knowledge of basic clinical principles. We determined that sex was not related to the assessment scores obtained by medical students.