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BackgroundLopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a and hydroxychloroquine efficacy for COVID-19 have been evaluated, but detailed evaluation is lacking.ObjectiveTo determine the efficacy of lopinavir/ritonavir, lopinavir/ritonavir-IFN-β-1a, hydroxychloroquine or remdesivir for improving the clinical, virological outcomes in COVID-19 inpatients.DesignOpen-label, randomized, adaptive, controlled trial.SettingMulti-center trial with patients from France.Participants583 COVID-19 inpatients requiring oxygen and/or ventilatory supportInterventionStandard of care (SoC, control), SoC plus lopinavir/ritonavir (400 mg lopinavir and 100 mg ritonavir every 12h for 14 days), SoC plus lopinavir/ritonavir plus IFN-ß-1a (44 μg of subcutaneous IFN-ß-1a on days 1, 3, and 6), SoC plus hydroxychloroquine (400 mg twice on day 1 then 400 mg once daily for 9 days) or SoC plus remdesivir (200 mg intravenously on day 1 then 100 mg once-daily for hospitalization duration or 10 days).MeasurementsThe primary outcome was the clinical status at day 15, measured by the WHO 7-point ordinal scale. Secondary outcomes included SARS-CoV-2 quantification in respiratory specimens and safety analyses.ResultsAdjusted Odds Ratio (aOR) for the WHO 7-point ordinal scale were not in favor of investigational treatments: lopinavir/ritonavirversuscontrol, aOR 0.83, 95%CI, 0.55 to 1.26, P=0.39; lopinavir/ritonavir-IFN-β-1aversuscontrol, aOR 0.69, 95%CI, 0.45 to 1.04, P=0.08; hydroxychloroquineversuscontrol, aOR 0.93, 95%CI, 0.62 to 1.41, P=0.75. No significant effect on SARS-CoV-2 RNA clearance in respiratory tract was evidenced. Lopinavir/ritonavir-containing treatments were significantly associated with more SAE.LimitationsNot a placebo-controlled, no anti-inflammatory agents tested.ConclusionNo improvement of the clinical status at day 15 nor SARS-CoV-2 RNA clearance in respiratory tract specimens by studied drugs. This comforts the recent Solidarity findings.RegistrationNCT04315948.FundingPHRC 2020, Dim OneHealth, REACTing

BACKGROUND Ischemic stroke is a prevalent, devastating disease with high morbidity and mortality. Despite extensive research using animal models, significant gaps remain in understanding the pathological processes in human stroke. We previously developed a tissue bank to analyze the blood immediately proximal and distal to an intracranial thrombus in patients undergoing mechanical thrombectomy (ClinicalTrials.gov identifier, NCT03153683). Our goal for the present project was to evaluate the blood gas changes and acid/base balance during stroke and determine how vascular collateralization affects these changes. METHODS We analyzed the blood samples and computed tomography angiography collateral scores from the first 62 patients in the BACTRAC (Blood and Clot Thrombectomy Registry and Collaboration) registry. The bicarbonate, partial pressure of oxygen, and partial pressure of carbon dioxide (pCO2) values of the intracranial (distal) and systemic (proximal) arterial blood relative to the occlusive thrombus were analyzed. Analysis of the group differences in systemic and intracranial blood gas values was also performed. RESULTS The partial pressure of oxygen, pCO2, and bicarbonate levels were all significantly higher in the systemic blood than in the intracranial blood (P < 0.001 for all) at thrombectomy. Collateralization did not significantly affect the distal blood gas values. Compared with the female patients, the male patients had had higher systemic pCO2 values (39.8 vs. 36.6 mm Hg; P = 0.0065) and lower systemic and intracranial pH values (7.351 vs. 7.392; P = 0.0047). CONCLUSIONS The arterial blood gases differed immediately proximal and distal to thrombi in large vessel occlusive stroke. Although vascular collateralization did not appear to affect the blood gas changes, some blood gas values differed between men and women. The changes in bicarbonate and pCO2 suggested a compensatory acid-base process occurring at the time of infarction.

Objective: to evaluate the efficacy and safety of glycosaminoglycan-peptide complex (GPC, Rumalon) used in patients with knee osteoarthritis (OA) and comorbidities (hypertension and/or type 2 diabetes mellitus (T2DM).Patients and methods: A 10-month multicenter (13 centers from 10 subjects of the Russian Federation) prospective study included 179 patients with Stages II–III primary tibiofemoral knee OA and comorbidity, a walking pain intensity of ≥40 mm on a visual analogue scale (VAS), and a need for nonsteroidal anti-inflammatory drugs (for at least 30 days in the previous 3 months). The efficiency of treatment was evaluated from the changes in VAS scores for knee pain intensity during walking, the overall WOMAC score and scores of its individual indicators, laboratory parameters, and ultrasound data. All the patients received 2 cycles of GPC treatment with 25 injections, by following the manufacturer's instructions.Results and discussion. Even at 2 months after starting the treatment, there was a statistically significant reduction in pain during walking from 60 (50–69) to 40 (27–53.5) mm on the VAS (p< 0.05), which persisted during the follow-up period. A similar pattern was found when assessing the WOMAC index and its components. The drug demonstrated an anti-inflammatory effect: a decrease in the number of patients with synovitis from 55.7 to 39.2% (p=0.02), the level of high-sensitivity C-reactive protein (hsCRP) from 3.2 (1.3–6.2) to 2.6 (1.2–5.7) mg/l (p< 0.05). GPC was ascertained to have a safety profile.Conclusion. The data of this study confirm the good therapeutic effect and safety of GPC Rumalon in knee OA patients with hypertension and/or T2DM. The drug is shown to have a rapid analgesic and anti-inflammatory effect, as well as a positive influence on all clinical manifestations of OA.

Risk of metastatic disease in the cluster 2-related pheochromocytoma/paraganglioma (PPGL) is low. In MEN2 patients, identification of origin of metastases from pheochromocytoma (PCC) or medullary thyroid carcinoma (MTC) is challenging as both are of neuroendocrine origin. We aim to describe our experience and perform a systematic review to assess prevalence, demographics, biochemistry, diagnostic evaluation, management, and predictors of cluster 2-related metastatic PPGL. Retrospective analysis of 3 cases from our cohort and 43 cases from world literature was done. For calculation of prevalence, all reported patients (n = 3063) of cluster 2 were included. We found that the risk of metastasis in cluster 2-related PPGL was 2.6% (2% in RET, 5% in NF1, 4.8% in TMEM127 and 16.7% in MAX variation). In metastatic PCC in MEN2, median age was 39 years, bilateral tumors were present in 71% and median tumor size was 9.7 cm (range 4–19) with 43.5% mortality. All patients had a primary tumor size ≥4 cm. Origin of primary tumor was diagnosed by histopathology of metastatic lesion in 11 (57.9%), 131I-MIBG scan in 6 (31.6%), and selective venous sampling and CT in 1 (5.3%) patient each. In subgroup of neurofibromatosis 1 (NF1), median age was 46 years (range 14–59) with median tumor size 6 cm and 57% mortality. To conclude, the risk of metastatic disease in cluster 2-related PPGL is low, being especially high in tumors with size ≥4 cm and associated with high mortality. One-third patients of NF1 with metastatic PPGL had presented in second decade of life. Long-term studies are needed to formulate management recommendations.

Diabetes is one of the four major non-communicable diseases, and appointed by the world health organization as the seventh leading cause of death worldwide. The scientists have turned over every rock in the corners of medical sciences in order to come up with better understanding and hence more effective treatments of diabetes. The continuous research on the subject has elucidated the role of immune disorders and inflammation as definitive factors in the trajectory of diabetes, assuring that blood glucose adjustments would result in a relief in the systemic stress leading to minimizing inflammation. On a parallel basis, microbial infections usually take advantage of immunity disorders and propagate creating a pro-inflammatory environment, all of which can be reversed by antimicrobial treatment. Standing at the crossroads between diabetes, immunity and infection, we aim in this review at projecting the interplay between immunity and diabetes, shedding the light on the overlapping playgrounds for the activity of some antimicrobial and anti-diabetic agents. Furthermore, we focused on the anti-diabetic drugs that can confer antimicrobial or anti-virulence activities.

The data on the congenital hyperinsulinism (CHI) in Asian Indian patients is limited. Diazoxide is often unavailable in India, which poses challenge in managing CHI. The study was aimed to present our experience with CHI with a special focus on the effectiveness and cost-effectiveness of octreotide long-acting release (OCT-LAR) among diazoxide-responsive CHI. The data of 14 index cases with CHI registered at our center were retrospectively analyzed. The diagnosis of CHI was based on elevated serum insulin (3.4–32.5 μIU/ml) and C-peptide (0.58–1.98 ng/ml) at the time of symptomatic hypoglycemia (BG≤41 mg/dl). Fourteen patients (13 males) presented at a median (range) age of 3 (1–270) days, seizures being the most common mode of presentation (78.6%). Ten patients were diazoxide-responsive, two were partially responsive, while two were unresponsive. Genetics was available for eight patients; ABCC8 (n=3, 1 novel) and HADH (n=2, both novel) were the most commonly mutated genes. OCT-LAR was offered to eight patients including four with diazoxide-responsive disease and was universally effective. We propose a cost-effective approach to use OCT-LAR in the management of CHI, which may also make it more cost-effective than diazoxide for diazoxide-responsive disease. Five of the 11 (45.5%) patients had evidence of neurological impairment; notably, two patients with HADH mutations had intellectual disability despite diazoxide-responsiveness. We report three novel mutations in CHI-associated genes. We demonstrate the effectiveness of and propose a cost-effective approach to use OCT-LAR in diazoxide-responsive CHI. Mutations in HADH may be associated with abnormal neurodevelopmental outcomes despite diazoxide-responsiveness.

espanolLa peritonitis secundaria es una patologia extremadamente delicada con una alta tasa de mortalidad, debido a las complicaciones que esta pude generar. Su tratamiento esta combinado entre antimicrobianos y el quirurgico, mediante la tecnica de laparoscopia en donde se debe contener el foco de infeccion, mediante la reseccion del organo afectado y drenaje del area purulenta. Se presenta caso clinico de paciente femenino de 17 anos de edad, que ingresa a centro de salud por presentar cuadro clinico de aproximadamente de 19 dias de evolucion, caracterizado por dolor abomino pelvico muy intenso de tipo colico, se acompanaba de nauseas y vomitos de tipo bilioso en varias ocasiones; refiere familiar ausencia de deposiciones una semana previa a su ingreso hospitalario en clinica San Francisco, donde es intervenida quirurgicamente, debido a apendicitis incidental y dolicomega sigma, diagnosticandose choque septico por peritonitis secundaria. En el presente caso de estudio, se observa el desarrollo de una apendicitis, que derivo en un abdomen agudo, desencadenandose una peritonitis secundaria. En el presente caso de estudio, se observa como el desarrollo de una apendicitis previa, derivo en un abdomen agudo, esencadenandose una peritonitis secundaria. En este contexto algunos de los sintomas de dolor abdominal concuerdan con la literatura, en el aspecto del dolor abdominal localizado o focalizado que en este particular la paciente refiere con nauseas y vomitos, no se presenta o describe alguna perforacion de la cavidad abdominal, por ello se puede clasificar como un abdomen agudo de tipo inflamatorio (peritonitico). A consecuencia de ello el paciente debe ser intubado e ingresado a UCI y se le realiza una relaparotomia para explorar y corregir los danos causados por la peritonitis en este contexto, con protocolo de antimicrobianos, sin embargo el paciente continua con una condicion critica, bajo sedacion, en constante monitoreo de su evolucion. EnglishSecondary peritonitis is an extremely delicate pathology with a high mortality rate, due to the complications that it can generate. Its treatment is combined between antimicrobial and surgical, through the laparoscopic technique where the focus of infection must be contained, through resection of the affected organ and drainage of the purulent area. A clinical case of a 17-year-old female patient is presented, who is admitted to the health center due to a clinical picture of approximately 19 days of evolution, characterized by very intense pelvic pain of the colic type, accompanied by nausea and vomiting of the bilious on several occasions; She refers to her family's absence of stools a week prior to her admission at the San Francisco clinic, where she undergoes surgery due to incidental appendicitis and dolicho mega sigma, diagnosing septic shock due to secondary peritonitis. In the present case study, it is observed how the development of a previous appendicitis led to an acute abdomen, triggering secondary peritonitis. In this context, some of the symptoms of abdominal pain agree with the literature, in the aspect of localized or focused abdominal pain that in this particular the patient refers with nausea and vomiting, no perforation of the abdominal cavity is presented or described, therefore It can be classified as an acute abdomen of an inflammatory type (peritonitic). As a result, the patient must be intubated and admitted to the ICU and a relaparotomy is performed to explore and correct the damage caused by peritonitis in this context, with an antimicrobial protocol, however the patient continues with a critical condition, under sedation, constantly monitoring its evolution

The widespread introduction into clinical practice of modern approaches to the treatment of rheumatoid arthritis (RA), the rational use of traditional and targeted antirheumatic drugs can effectively suppress inflammatory activity, restrain the progression of the disease and improve the quality of life of patients. At the same time, in some patients, even after the repeated change of targeted drugs, it is not possible to achieve the target level of RA activity. Serious difficulties arising in the management of such patients raised the question of identifying a special variant of the disease – difficult-to-treat (D2T) RA. The presence of various variants of D2T RA and the need to use a personalized approach to therapy justify the creation of special recommendations for the management of this category of patients. The first step in preparing these recommendations was the definition of D2T RA recently presented by the EULAR working group. It includes three criteria: 1) insufficient effectiveness of the therapy; 2) the presence of an active symptomatic disease; 3) clinical perception.

Objective: comparison of the accuracy of risk assessment of low-energy fractures in patients with rheumatoid arthritis (RA) using the prognostic model developed at V.A. Nasonova Research Institute of Rheumatology, and the Russian model of the FRAX algorithm.Patients and methods. A prospective long-term observational non-interventional study included 70 women aged 40–80 years with a definite diagnosis of RA (ACR, 1987). All patients underwent dual-energy X-ray absorptiometry at baseline and over time; clinical and anamnestic data were analyzed, including information on fractures that occurred during the observation period, confirmed by medical documents.Results and discussion. The sensitivity and specificity of the FRAX algorithm were 67 and 56%, the sensitivity and specificity of the prognostic model of V.A. Nasonova Research Institute of Rheumatology – 78 and 56%, respectively. The diagnostic accuracy of the FRAX algorithm and the predictive model was 58 and 61%, respectively.Conclusion. The predictive model developed at V.A. Nasonova Research Institute of Rheumatology, showed higher diagnostic accuracy and sensitivity, as well as comparable specificity with the FRAX algorithm in assessing fractures in RA patients.

Modern therapy of osteoarthritis (OA) consists of four sequential stages and includes non-pharmacological, pharmacological and surgical methods of treatment, and also assumes the possibility of collaborative management of the patient by doctors of different specialties, which allows to optimize the processes of diagnosis and treatment. The article presents simple and convenient algorithms, including diagnostic criteria, options for providing medical care, as well as situations (so-called red flags) that require referral of a patient to a specialist, primarily a rheumatologist. It has been demonstrated that the early use of the well-proven SYSADOA in any localization of OA, in particular the combined drugs of chondroitin sulfate and glucosamine, can increase the effectiveness of treatment, reduce possible functional disorders, and minimize the adverse effects of analgesic therapy.

Potential discrepancies between laboratory and estimated (from Continuous Glucose Monitoring (CGM)) glycated hemoglobin (HbA1c) have been reported by diabetologists. CGM devices produce an eA1c derived from average glucose and correlated with Time-in-Range (TIR, %) which is the relative time spent in a range of normal glycaemia. Through a case report, we studied the potential causes for these discrepancies. CGM devices estimate eA1c during the lifespan of the sensor, that is replaced every 14 days and HbA1c is a retrospective data of exposure to hyperglycemia over 8 to 12 weeks. In our case report, the patient had a poor glycemic control resulting in 9% eA1c compared to 7,4% HbA1c got by delocalized immune-assay (Siemens DCA-Vantage®), confirmed at 7,7% by HPLC (Variant II Turbo). On top of the CGM data, an increased labile A1c (LA1c) fraction was found on the patient's HbA1c HPLC profile, both in favor of a recently altered glycemic control. Thus, recent and/or substantial variations in glycemic control will increase the gap between HbA1c and eA1c, being a potential source of therapeutic errors. The differences of those markers, particularly the time window during which it is estimated, make them hardly comparable. As the use of CGM is becoming widespread, it is important to understand and harness its data and biomarkers.

Upadacitinib (UPA), a JAK inhibitor, is a new therapeutic option that allows patients with insufficient response to therapy with basic anti-inflammatory drugs (DMARDs) or genetically engineered biological drugs (GEBDs) to achieve the goals of therapy for rheumatoid arthritis (RA). Despite the availability of convincing data from international randomized clinical trials, there is insufficient information about the efficacy and safety profile of UPA, the quality of life of patients receiving the drug in real clinical practice.Aim of the study – to assess the efficacy and tolerability of the UPA drug at a dose of 15 mg/day in patients with rheumatoid arthritis with moderate and high disease activity and to assess their quality of life in real clinical practice.Materials and methods. The study included 41 patients with RA with insufficient effect of previous therapy with DMARDs or GEBDs, persisting moderate or high disease activity, who were initiated with UPA therapy in 7 rheumatological centers of the Russian Federation. To assess the activity of the disease, standard indices were used: DAS28- ESR, DAS28-CRP, SDAI, CDAI. Functional ability was assessed according to the HAQ questionnaire, quality of life – according to the EQ-5D questionnaire, the activity of the disease according to the patient’s opinion – according to the RAPID-3 index. The HADS scale was used to identify the states of depression, anxiety and emotional disorder.Results. During the first week of taking the drug, there was a marked decrease in pain from 60 to 30 mm on a visual analogue scale, which lasted until the third month of therapy. There was a statistically significant decrease in morning stiffness, the number of painful and swollen joints, health assessments by the doctor and patient, erythrocyte sedimentation rate and C-reactive protein (p≤0.001). A decrease in disease activity was also noted according to the dynamics of the activity indices DAS28, SDAI, CDAI (pConclusions. The first results of the use of UPA in RA patients with insufficient efficacy of previous therapy with DMARDs or GEBDs in real clinical practice indicate its efficacy and safety, an improvement in the functional state and quality of life of patients by the 12th week of the study.

Background The symptom burden associated with cancer and its treatment can negatively affect patients’ quality of life and survival. Symptom-focused collaborative care model (CCM) interventions can improve outcomes, but only if patients engage with them. We assessed the receptivity of severely symptomatic oncology patients to a remote nurse-led CCM intervention. Methods In a pragmatic, cluster-randomized, stepped-wedge trial conducted as part of the National Cancer Institute IMPACT Consortium (E2C2, NCT03892967), patients receiving cancer care were asked to rate their sleep disturbance, pain, anxiety, emotional distress, fatigue, and limitations in physical function. Patients reporting at least 1 severe symptom (≥7/10) were offered phone consultation with a nurse symptom care manager (RN SCM). Initially, patients had to “opt-in” to receive a call, but the protocol was later modified so they had to “opt-out” if they did not want a call. We assessed the impact of opt-in vs opt-out framing and patient characteristics on receptiveness to RN SCM calls. All statistical tests were 2-sided. Results Of the 1204 symptom assessments (from 864 patients) on which at least 1 severe symptom was documented, 469 (39.0%) indicated receptivity to an RN SCM phone call. The opt-out period (odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.12 to 2.32, P = .01), receiving care at a tertiary care center (OR = 3.59, 95% CI = 2.18 to 5.91, P < .001), and having severe pain (OR = 1.80, 95% CI = 1.24 to 2.62, P = .002) were associated with statistically significantly greater willingness to receive a call. Conclusions Many severely symptomatic patients were not receptive to an RN SCM phone call. Better understanding of reasons for refusal and strategies for improving patient receptivity are needed.

Background:Microbiological surveillance of bronchoscopes and automatic endoscope reprocessors (AERs)/washer disinfectors as a quality control measure is controversial. Experts also are divided on the infection risks associated with bronchoscopic procedures.Objective:We evaluated the impact of routine microbiological surveillance and audits of cleaning/disinfection practices on contamination rates of reprocessed bronchoscopes.Design:Audits were conducted of reprocessing procedures and microbiological surveillance on all flexible bronchoscopes used from January 2007 to June 2020 at a teaching hospital in France. Contamination rates per year were calculated and analyzed using a Poisson regression model. The risk factors for microbiological contamination were analyzed using a multivariable logistical regression model.Results:In total, 478 microbiological tests were conducted on 91 different bronchoscopes and 57 on AERs. The rate of bronchoscope contamination significantly decreased between 2007 and 2020, varying from 30.2 to 0% (P < .0001). Multivariate analysis confirmed that retesting after a previous contaminated test was significantly associated with higher risk of bronchoscope contamination (OR, 2.58; P = .015). This finding was explained by the persistence of microorganisms in bronchoscopes despite repeated disinfections. However, the risk of persistent contamination was not associated with the age of the bronchoscope.Conclusions:Our results confirm that bronchoscopes can remain contaminated despite repeated reprocessing. Routine microbial testing of bronchoscopes for quality assurance and audit of decontamination and disinfection procedures can improve the reprocessing of bronchoscopes and minimize the rate of persistent contamination.

Objective Literature regarding utility of 68 Ga-DOTATATE PET/CT in insulinoma localization across various subgroups [benign/malignant/multiple endocrine neoplasia-1 (MEN-1) syndrome associated] remains scarce. In this study, the performance of 68 Ga-DOTATATE PET/CT was compared with contrast-enhanced computed tomography (CECT) and 68 Ga-NODAGA-Exendin-4 PET/CT (whenever available) in an endogenous hyperinsulinemic hypoglycemia (EHH) cohort. Design Retrospective audit. Patients EHH patients [N = 36, lesions (n) = 49, final diagnosis: benign sporadic insulinoma (BSI) (N = 20), malignant insulinoma (N = 4, n = 14), MEN-1 syndrome associated insulinoma (N = 9, n = 15), Munchausen syndrome (N = 2) and drug-induced hypoglycemia (N = 1)] having both preoperative imaging modalities (CECT and 68 Ga-DOTATATE PET/CT). Measurements Per-lesion sensitivity (Sn) and positive predictive value (PPV) for histopathological diagnosis of insulinoma. Results Sn and PPV of 68 Ga-DOTATATE PET/CT were 67.3% and 89.2%; 55% and 100%; 85.7% and 100%; and 66.7% and 77% for overall EHH, BSI, malignant, and MEN-1 syndrome associated insulinoma cohorts respectively. Despite having comparatively lower sensitivity in BSI cohort, 68 Ga-DOTATATE PET/CT localized a pancreatic tail lesion missed by other modalities. 68 Ga-DOTATATE PET/CT had comparatively higher sensitivity in malignant insulinoma than BSI cohort. 68 Ga-DOTATATE PET/CT also paved the way for successful response to 177 Lu-based peptide receptor radionuclide therapy (PRRT). In MEN-1 cases, lower PPV as compared with BSI was due to uptake in non-insulinoma pancreatic neuroendocrine tumours (Pan-NET). Conclusions 68 Ga-DOTATATE PET/CT has supplemental role in selected cases of BSI with negative and/or discordant results with CECT and 68 Ga-NODAGA-Exendin-4 PET/CT. In malignant insulinoma, 68 Ga-DOTATATE-PET/CT has an additional theranostic potential. Interference due to uptake in non-insulinoma Pan-NET in MEN-1 syndrome may hinder insulinoma localization with 68 Ga-DOTATATE-PET/CT.

Debilitating diseases of the eye represent a large unmet medical need potentially addressable with stem cell‐based approaches. Over the past decade, the California Institute for Regenerative Medicine (CIRM) has funded and supported the translation, from early research concepts to human trials, of therapeutic stem cell approaches for dry age‐related macular degeneration, retinitis pigmentosa, and limbal stem cell deficiency. This article chronicles CIRM's journey in the ophthalmology field and discusses some key challenges and questions that were addressed along the way as well as questions that remain., Cell‐based therapies comprised of or derived from stem/progenitor cells are being developed to treat debilitating eye diseases such as dry age‐related macular degeneration (AMD), retinitis pigmentosa (RP), and limbal stem cell deficiency (LSD). Shown are the routes of delivery and location within the eye of the specific cell therapies discussed in this article. Adapted from https://www.freepik.com/premium-vector/eye-anatomy-vector_760161.htm.

Background Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients. Objective and design We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome. Subjects and methods We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay. Results Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of −1.99 (95% confidence interval [CI] −2.36 to −1.62), −1.98 (95% CI −2.94 to −1.02), −2.20 (95% CI −3.15 to −1.25) and − 2.10 (95% CI −3.29 to −0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05). Conclusions This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.

In March 2020, the Australian government introduced a raft of public health initiatives to curb the rising cases of coronavirus disease 2019 (COVID-19) including closing schools and work from home orders. As a group of female academics, we were immediately attuned to the potential of COVID-19 to dilute progress made towards reducing the academic gender gap. This study emerged in response and comprised a rapid gender impact assessment of Australian universities’ organisational responses to COVID-19. Our aim was to understand the nature of university policy responses and the extent to which they considered differential impacts for men and women. We searched for relevant communications pertaining to COVID-19 policies from all Australian universities published up to June 2020. Our final sample comprised 79 documents from 29 universities. Information collected was in relation to five key policy domains: support for higher degree research students, leave arrangements for staff, working remotely, managing staff and academic promotion. Overall, little attention was paid to how gender might impact on the need for, or access to, policies in response to COVID-19. Findings showed a reliance on existing workplace mechanisms including access to leave and flexible working arrangements. While the ability to work flexibly is considered a key enabler of gender equality, these approaches have been in place at Australian universities for decades but have, on their own, been inadequate to redress entrenched inequalities. While there is potential for social disruptions brought about by the pandemic to act as a catalyst for change, this will not happen without policies that are transformative in their approach to equality and inclusion.

BackgroundEvidence-based international expert consensus regarding the impact of peripheral nerve block (PNB) use in total hip/knee arthroplasty surgery.MethodsA systematic review and meta-analysis: randomized controlled and observational studies investigating the impact of PNB utilization on major complications, including mortality, cardiac, pulmonary, gastrointestinal, renal, thromboembolic, neurologic, infectious, and bleeding complications.Medline, PubMed, Embase, and Cochrane Library including Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, were queried from 1946 to August 4, 2020.The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess evidence quality and for the development of recommendations.ResultsAnalysis of 122 studies revealed that PNB use (compared with no use) was associated with lower ORs for (OR with 95% CIs) for numerous complications (total hip and knee arthroplasties (THA/TKA), respectively): cognitive dysfunction (OR 0.30, 95% CI 0.17 to 0.53/OR 0.52, 95% CI 0.34 to 0.80), respiratory failure (OR 0.36, 95% CI 0.17 to 0.74/OR 0.37, 95% CI 0.18 to 0.75), cardiac complications (OR 0.84, 95% CI 0.76 to 0.93/OR 0.83, 95% CI 0.79 to 0.86), surgical site infections (OR 0.55 95% CI 0.47 to 0.64/OR 0.86 95% CI 0.80 to 0.91), thromboembolism (OR 0.74, 95% CI 0.58 to 0.96/OR 0.90, 95% CI 0.84 to 0.96) and blood transfusion (OR 0.84, 95% CI 0.83 to 0.86/OR 0.91, 95% CI 0.90 to 0.92).ConclusionsBased on the current body of evidence, the consensus group recommends PNB use in THA/TKA for improved outcomes.Recommendation: PNB use is recommended for patients undergoing THA and TKA except when contraindications preclude their use. Furthermore, the alignment of provider skills and practice location resources needs to be ensured. Evidence level: moderate; recommendation: strong.

Patient's satisfaction with treatment is a fundamental indicator of the quality of medical care, which is especially important for assessing the effectiveness of therapy for musculoskeletal pain in rheumatic diseases (RD).Objective: to determine satisfaction of patients with RD with pain relief therapy and to analyze the factors influencing the subjective assessment of analgesic therapy.Patients and methods. Anonymous survey of 1040 patients (age 55.8±14.0 years, 76.8% were women) with RD, rheumatoid arthritis (RA), osteoarthritis (OA), spondyloarthritis, systemic connective tissue diseases and gout, was carried out. The presence of pain and its therapy, satisfaction with treatment, and patient's opinion about the reasons of low pain relief effectiveness were assessed. The dependence of the presence of dissatisfaction with treatment on a number of demographic and clinical factors was analyzed.Results and discussion. 71.5% of patients experienced pain in one or more joint areas and/or in the back. 70.6% of patients used non-steroidal antiinflammatory drugs (NSAIDs), 1.6% – paracetamol, 40.0% – non-drug modalities and methods of alternative medicine. 15.6% of the respondents were completely satisfied with the treatment, 64.0% were partially satisfied, and 20.4% were completely dissatisfied. The main subjective reasons for the insufficient effectiveness of analgesic therapy were: fear of taking prescribed medications due to possible complications (45.4%), low effectiveness of drugs (15.7%), insufficient attention of doctors (20.3%). Male gender, body mass index >30 kg/m2 , severe pain, pain in several areas, and the diagnosis of OA were statistically significantly associated with treatment dissatisfaction. In contrast, patients with RA showed greater satisfaction with treatment.Conclusion. Most patients with RD are dissatisfied with the results of pain therapy. Educational work with patients and a personalized approach to prescribing analgesic therapy is needed.

Osteoarthritis (OA) is the most common disease of the elderly, which is accompanied by pain and damages all tissues of the joint. OA is associated with progressive loss of articular cartilage, sclerotic changes in the subchondral bone and the formation of osteophytes. Cartilage destruction is caused by resorption of the extracellular matrix, which consists mainly of type II collagen and aggrecan proteoglycan. Excessive cleavage of type II collagen in OA is associated with increased synthesis and activity of metalloproteinases and the expression of pro-inflammatory cytokines of interleukin 1β and tumor necrosis factor α. Currently, OA therapy is symptomatic, often ineffective, and in some cases is accompanied by adverse side effects. Therefore, the search for new therapeutic approaches to the treatment of the disease, using modern technological capabilities and knowledge of the metabolic disorders that cause the disease. The review presents new promising methods in the treatment of OA using stem cells and subcellular structures, based on modern knowledge of molecular and cellular mechanisms that are disrupted during development and disease progression.

The review provides a brief description of the clinical and serological markers of antiphospholipid syndrome (APS), risk factors for the development and recurrence of thrombosis in APS. A complete description of the GAPSS and its simplified (corrected) version, adjusted GAPSS (aGAPSS), as well as the DIAPS, is presented. These scales allow one to determine the activity of APS and reflect the range of cumulative and/or irreversible damage due to the disease.

Currently chondroitin sulfate (CS) is the most studied drug from the group of «chondroprotectors». The article shows the role of CS in the treatment of osteoarthritis (OA): mechanism of action, clinical efficacy and safety in patients with OA with comorbidity. Evidence for the effectiveness and safety of the use of CS has been analyzed. The place of this drug in Russian and international clinical guidelines for the management of patients with OA is discussed.In domestic practice, the parenteral form of CS is often used in patients with OA. The parenteral form of CS for intramuscular and intra-articular administration (Chondroguard®) has a number of advantages, including the rapid onset of the effect. This enables reducing the dose in a short time or completely abandon the use of non-steroidal anti-inflammatory drugs (NSAIDs), which is extremely important for patients with OA with comorbidity. Chondroguard®can be recommended for initial use in exacerbations of chronic joint and back pain in OA, including in patients with relative and absolute contraindications for NSAID therapy.

The article discusses various options for the management of patients with rheumatoid arthritis (RA) in accordance with modern foreign and domestic recommendations. Data on the possibility of achieving an effect on the background of monotherapy with methotrexate (MT) are presented and options for more active therapy are discussed. The authors compare the effectiveness of sequential change of basic anti-inflammatory drugs (DMARDs), sequential addition of DMARDs to MT, treatment with a triple combination of DMARDs with an inadequate response to MT or in the debut of therapy, combination of DMARDs and biological drugs. According to the study data, in cohorts of patients with equal clinical effectiveness of the triple combination of DMARDs and the combination of DMARDs with biological drugs, however, the severity of the progression of destruction in the joints of the hands and feet is less when using biological agents. It was noted that the evaluation of the effectiveness of the double / triple combination of DMARDs was carried out in open observational studies, which has less evidence value than randomized controlled double-blind placebo-controlled trials (RCTs) for the assessment of biological drugs. Despite the importance of implementing biological drugs in clinical practice, their high cost limits their use by patients. Registration in the Russian Federation of the first biosimilar of etanercept (ETN) - the drug Erelzi is important for the treatment of patients with RA. The article describes the advantages of original ETN (tumor necrosis factor ainhibitor - iFNO a) over other iFNO a, which are monoclonal antibodies to this cytokine. The article presents data on the equivalence of the ETN biosimilar registered in the Russian Federation (Erelzi) with the original ETN in terms of clinical efficacy, safety and immunogenicity. The comparability of drugs in terms of the frequency of adverse events was demonstrated. It is shown that switching from the original ETN to its biosimilar allows you to maintain the effect, not accompanied by an increase in the frequency of intolerance or immunogenicity. It is indicated that Erelzi is registered in the Russian Federation for the treatment of RA, various variants of axial spondylitis, psoriatic arthritis, psoriasis and juvenile idiopathic arthritis.

We present a clinical case of combination of axial spondyloarthritis (axSpA) and chronic recurrent skin lesions in the form of acne conglobata, hidradenitis suppurativa (HS) with fistulous tracts formation. During the diagnostic search, the following diseases were considered: HS, SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis), PASS syndrome (pyoderma gangrenosum, acne, ankylosing spondylitis, HS). The choice of therapy in this patient and the possibility of using biologic disease-modifying antirheumatic drugs for axSpa and concomitant autoinflammatory skin process are discussed.

We present two clinical cases: the first patient had combination of antiphospholipid syndrome (APS) and melanoma, and the second – systemic lupus erythematosus (SLE) and APS, melanoma, infiltrative tuberculosis and Herpes zoster. Managing patients with SLE combined with APS is really challenging. Infections and malignant neoplasms, along with kidney damage and cardiovascular diseases, are a significant cause of death in this cohort of patients. The role of antibodies to phospholipids in the onset of malignancy is still under discussion. The combination of rheumatic diseases with oncological or infectious pathology complicates therapy, limiting the use of drugs, recommended by clinical guidelines.

In mid-2021, the SARS-CoV-2 (Severe Acute Respiratory coronavirus 2) infection, which caused the coronavirus disease (COVID-19) pandemic, affected more than 157 million people in all regions of the world and led to more than 3.2 million deaths. It is assumed that elderly age, uncontrolled inflammation, anti-inflammatory therapy, comorbid pathology, genetic and other factors can potentially lead to an increase in “sensitivity” to viral and bacterial infections, including SARS-CoV-2. The new version of the recommendations of the Association of Rheumatologists of Russia formulates the main provisions concerning the tactics of managing patients with Immune-mediated Rheumatic Diseases during the ongoing COVID-19 pandemic.

A foundational strategy to promote implementation of evidence-based interventions (EBIs) is providing EBI training to therapists. This study tested an online training system in which therapists practiced observational coding of mock video vignettes demonstrating family therapy techniques for adolescent behavior problems. The study compared therapists ratings to gold-standard scores to measure therapist reliability (consistency across vignettes) and accuracy (approximation to gold scores); tested whether reliability and accuracy improved during training; and tested therapist-level predictors of overall accuracy and change in accuracy over time. Participants were 48 therapists working in nine community behavioral health clinics. The 32-exercise training course provided online instruction (about 15 min/week) in 13 core family therapy techniques representing three modules: Family Engagement, Relational Orientation, Interactional Change. Therapist reliability in rating technique presence (i.e., technique recognition) remained moderate across training; reliability in rating extensiveness of technique delivery (i.e., technique judgment) improved sharply over time, from poor to good. Whereas therapists on average overestimated extensiveness for almost every technique, their tendency to give low-accuracy scores decreased. Therapist accuracy improved significantly over time only for Interactional Change techniques. Baseline digital literacy and submission of self-report checklists on use of the techniques in their own sessions predicted coding accuracy. Training therapists to be more reliable and accurate coders of EBI techniques can potentially yield benefits in increased EBI self-report acumen and EBI use in daily practice. However, training effects may need to improve from those reported here to avail meaningful impact on EBI implementation. Trial Registration: The parent clinical trial is registered at www.ClinicalTrials.gov , ID: NCT03342872 (registration date: 11.10.17).

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8–0.9 per week increase; p Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

WOS:000613461600006 PubMed ID: 32926494 Objectives To evaluate the maternal and perinatal outcomes of pregnancies affected by SARS-CoV-2 infection. Methods This was a multinational retrospective cohort study including women with a singleton pregnancy and laboratory-confirmed SARS-CoV-2 infection, conducted in 72 centers in 22 different countries in Europe, the USA, South America, Asia and Australia, between 1 February 2020 and 30 April 2020. Confirmed SARS-CoV-2 infection was defined as a positive result on real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab specimens. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit (ICU), use of mechanical ventilation and death. Results In total, 388 women with a singleton pregnancy tested positive for SARS-CoV-2 on RT-PCR of a nasopharyngeal swab and were included in the study. Composite adverse maternal outcome was observed in 47/388 (12.1%) women; 43 (11.1%) women were admitted to the ICU, 36 (9.3%) required mechanical ventilation and three (0.8%) died. Of the 388 women included in the study, 122 (31.4%) were still pregnant at the time of data analysis. Among the other 266 women, six (19.4% of the 31 women with first-trimester infection) had miscarriage, three (1.1%) had termination of pregnancy, six (2.3%) had stillbirth and 251 (94.4%) delivered a liveborn infant. The rate of preterm birth before 37 weeks' gestation was 26.3% (70/266). Of the 251 liveborn infants, 69/251(27.5%) were admitted to the neonatal ICU, and there were five (2.0%) neonatal deaths. The overall rate of perinatal death was 4.1% (11/266). Only one (1/251, 0.4%) infant, born to a mother who tested positive during the third trimester, was found to be positive for SARS-CoV-2 on RT-PCR. Conclusions SARS-CoV-2 infection in pregnant women is associated with a 0.8% rate of maternal mortality, but an 11.1% rate of admission to the ICU. The risk of vertical transmission seems to be negligible. (C) 2020 International Society of Ultrasound in Obstetrics and Gynecology.

The article presents a case of periodic fever (PF) in a 35-year-old patient, who did not have hereditary and proven genetic factors of the disease, which was characterized by an atypical course with variable in duration and frequency severe abdominal pain and febrile fever attacks, increased acute phase reactants and ineffectiveness of colchicine intake. Differential diagnosis with a wide range of febrile conditions was performed. Daily subcutaneous therapy of interleukin 1 inhibitor (iIL1) at a dose of 100 mg was used as a diagnostic marker to confirm the diagnosis of PF. As a result of the therapy, a rapid (within a few hours after injection) relief of the current attack of the disease, normalization of serum CRP levels, and further complete control over the disease (no relapses) were achieved. Our observation shows that a positive response to iIL1 therapy can serve as a diagnostic marker of PF.

The purpose of this study was to determine the profile of immunoreactants deposited in intact skin biopsies from the patients with confirmed and probable systemic lupus erythematosus. The study involved 94 patients who, along with a standard clinical and laboratory examination, underwent a biopsy of clinically healthy skin in the deltoid muscle area (lupus band test). The nature and combination of immune deposits in the skin, the strength of immunofluorescence, and the location were evaluated. In the patients with significant systemic lupus erythematosus (n = 56), lupus band test was positive in 60.7 % of the cases and correlated with disease activity according to SLEDAI 2K (p = 0.001). At the same time, the skin biopsy often revealed the immunoreactant IgM (85.3 %), the degree of fluorescence of which had direct correlations with the increased level of antibodies to dsDNA (p 0.05). In the examined patients with probable systemic lupus erythematosus, positive lupus band test was detected in 47 % of cases, and IgM was detected in 72.2% of patients, which brought them closer to the group of patients with confirmed systemic lupus erythematosus. However, 33.3% of patients with probable systemic lupus erythematosus had isolated deposits of any one immunoreactant, while the association of immunoreactants (IgM+IgG) and (IgM+IgG+C3) characteristic of confirmed systemic lupus erythematosus occurred in only 27.7 and 5.5% of cases, respectively. It should be noted that the C1q immunoreactant was detected in the skin biopsies with both confirmed (38.2%) and probable systemic lupus erythematosus (39%). The data obtained suggest that lupus band test with the presence of a specific pattern of immunoreactants can be used as an additional diagnostic test for the diagnosis of systemic lupus erythematosus.

Difficulties in treating patients with rheumatological diseases are due to the complexity and versatility of pathogenesis, frequent comorbidity and advanced age of the majority of such patients. The use of non-pharmacological methods of treatment, including physical methods, enhances the analgesic and anti-inflammatory effect, improves tissue trophism and promotes the activation of reparative processes, slows down the progression of the disease and generally improves the quality of life of patients. In the complex treatment and rehabilitation of rheumatological patients, the use of magnetotherapy seems to be a method that is well substantiated by the data of numerous fundamental and modern clinical studies.

The development of irreversible organ damage (IOD) in systemic lupus erythematosus (SLE) significantly increases the risk of death, worsens the quality of life and significantly increases the cost of treatment. The development and implementation of specific tools that will promote early identification of the risk of unfavorable outcomes is a priority. The article presents literature review on a new method for prediction of unfavorable outcomes in SLE – frailty index (FI, vulnerability index). FI, developed by a group of international experts on the basis of the database of the international cohort of SLE patients – SLICC (Systemic Lupus International Collaborating Clinics) – is easily reproducible in real clinical practice and can be used in patients with an early stage of SLE to predict the risk of death, the development of IOD. and hospitalization. The SLE Forecasting index of unfavorable outcomes (SLICC-FI) appears to be a promising clinical and research tool for identifying those who need more careful monitoring and an individual therapeutic strategy at an early stage of the disease.

Osteoarthritis (OA) is the most common pathology of the musculoskeletal system and is a serious medical and social problem. OA is of particular importance in elderly and senile people due to the high frequency of comorbid pathology. Pain relief is a priority in the formation of individual therapeutic programs for patients with OA, starting from their first request for medical assistance. At the same time, due to the ambiguity of existing clinical recommendations, most experts note a number of difficulties in prescribing treatment for patients with OA.The article presents a consensus position of experts regarding a complex approach to the choice of therapy in patients with OA at the initial visit to the doctor. The article discusses: current clinical guidelines for the management of patients with OA; most common problems in the management of patients with OA in real clinical practice; goals of treatment strategies for OA taking into account the risk factors for its progression; an algorithm of pain relief during initial treatment in patients with OA; prevention of OA exacerbations with the use of basic structure-modifying drugs; recommendations for the choice of non-steroidal anti-inflammatory drugs.According to experts, a rational approach to the treatment of OA is based on the combined use of non-drug and pharmacological methods with constant monitoring of therapy regimens and side effects. These recommendations can be considered disease-modifying strategies that in many cases allow improving functional status and achieving long-term remission in patients with OA.

The COVID-19 pandemic has generated many concerns about cross-contamination risks, particularly in hospital settings and Intensive Care Units (ICU). Virus-laden aerosols produced by infected patients can propagate throughout ventilated rooms and put medical personnel entering them at risk. Experimental results found with a schlieren optical method have shown that the air flows generated by a cough and normal breathing were modified by the oxygenation technique used, especially when using High Flow Nasal Canulae, increasing the shedding of potentially infectious airborne particles. This study also uses a 3D Computational Fluid Dynamics model based on a Lattice Boltzmann Method to simulate the air flows as well as the movement of numerous airborne particles produced by a patient’s cough within an ICU room under negative pressure. The effects of different mitigation scenarii on the amount of aerosols potentially containing SARS-CoV-2 that are extracted through the ventilation system are investigated. Numerical results indicate that adequate bed orientation and additional air treatment unit positioning can increase by 40% the number of particles extracted and decrease by 25% the amount of particles deposited on surfaces 45s after shedding. This approach could help lay the grounds for a more comprehensive way to tackle contamination risks in hospitals, as the model can be seen as a proof of concept and be adapted to any room configuration.

Purpose Colorectal cancer (CRC) is the second most deadly cancer in the USA. Early detection can improve CRC outcomes, but recent national screening rates (62%) remain below the 80% goal set by the National Colorectal Cancer Roundtable. Multiple options are endorsed for average-risk CRC screening, including the multi-target stool DNA (mt-sDNA) test. We evaluated cross-sectional mt-sDNA test completion in a population of commercially and Medicare-insured patients. Methods Participants included individuals ages 50 years and older with commercial insurance or Medicare, with a valid mt-sDNA test shipped by Exact Sciences Laboratories LLC between January 1, 2018, and December 31, 2018 (n = 1,420,460). In 2020, we analyzed cross-sectional adherence, as the percent of successfully completed tests within 365 days of shipment date. Results Overall cross-sectional adherence was 66.8%. Adherence was 72.1% in participants with Traditional Medicare, 69.1% in participants with Medicare Advantage, and 61.9% in participants with commercial insurance. Adherence increased with age: 60.8% for ages 50–64, 71.3% for ages 65–75, and 74.7% for ages 76 + years. Participants with mt-sDNA tests ordered by gastroenterologists had a higher adherence rate (78.3%) than those with orders by primary care clinicians (67.2%). Geographically, adherence rates were highest among highly rural patients (70.8%) and ordering providers in the Pacific region (71.4%). Conclusions Data from this large, national sample of insured patients demonstrate high cross-sectional adherence with the mt-sDNA test, supporting its role as an accepted, noninvasive option for average-risk CRC screening. Attributes of mt-sDNA screening, including home-based convenience and accompanying navigation support, likely contributed to high completion rates.

The epidemiology of Yersinia pestis, the causative agent of plague, involves vectors and reservoirs in its transmission cycle. The passive plague surveillance in Madagascar targets mainly rodent and fleas. However, carnivores are routinely surveyed as sentinels of local plague activity in some countries. The aim of this study is to assess the use of domestic dog (Canis familiaris) as sentinel animal for field surveillance of plague in a highly endemic area in Madagascar. Cross-sectional surveys of plague antibody prevalence in C. familiaris were conducted in endemic areas with contrasting histories of plague cases in humans, as well as a plague free area. Rodent capture was done in parallel to evaluate evidence for Y. pestis circulation in the primary reservoirs. In 2 sites, dogs were later re-sampled to examine evidence of seroconversion and antibody persistence. Biological samplings were performed between March 2008 and February 2009. Plague antibody detection was assessed using anti-F1 ELISA. Our study showed a significant difference in dog prevalence rates between plague-endemic and plague-free areas, with no seropositive dogs detected in the plague free area. No correlation was found between rodents and dog prevalence rates, with an absence of seropositive rodents in some area where plague circulation was indicated by seropositive dogs. This is consistent with high mortality rates in rodents following infection. Re-sampling dogs identified individuals seropositive on both occasions, indicating high rates of re-exposure and/or persistence of plague antibodies for at least 9 months. Seroconversion or seropositive juvenile dogs indicated recent local plague circulation. In Madagascar, dog surveillance for plague antibody could be useful to identify plague circulation in new areas or quiescent areas within endemic zones. Within active endemic areas, monitoring of dog populations for seroconversion (negative to positive) or seropositive juvenile dogs could be useful for identifying areas at greatest risk of human outbreaks.

Background EEG-based prognostication studies in intensive care units often rely on a standard 21-electrode montage (stdEEG) requiring substantial human, technical, and financial resources. We here evaluate whether a simplified 4-frontal electrode montage (4-frontEEG) can detect EEG patterns associated with poor outcomes in adult patients under veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods We conducted a reanalysis of EEG data from a prospective cohort on 118 adult patients under VA-ECMO, in whom EEG was performed on admission to intensive care. EEG patterns of interest included background rhythm, discontinuity, reactivity, and the Synek’s score. They were all reassessed by an intensivist on a 4-frontEEG montage, whose analysis was then compared to an expert’s interpretation made on stdEEG recordings. The main outcome measure was the degree of correlation between 4-frontEEG and stdEEG montages to identify EEG patterns of interest. The performance of the Synek scores calculated on 4-frontEEG and stdEEG montage to predict outcomes (i.e., 28-day mortality and 90-day Rankin score $${\ge {4}}$$ ≥ 4 ) was investigated in a secondary exploratory analysis. Results The detection of EEG patterns using 4-frontEEG was statistically similar to that of stdEEG for background rhythm (Spearman rank test, ρ = 0.66, p $$\kappa$$ κ = 0.955), reactivity ($$\kappa$$ κ = 0.739) and the Synek’s score (ρ = 0.794, p 4-frontEEG and stdEEG montages in predicting 28-day mortality (AUC 4-frontEEG 0.71, AUC stdEEG 0.68) and for 90-day poor neurologic outcome (AUC 4-frontEEG 0.71, AUC stdEEG 0.66). An exploratory analysis confirmed that the Synek scores determined by 4 or 21 electrodes were independently associated with 28-day mortality and poor 90-day functional outcome. Conclusion In adult patients under VA-ECMO, a simplified 4-frontal electrode EEG montage interpreted by an intensivist, detected common EEG patterns associated with poor outcomes, with a performance similar to that of a standard EEG montage interpreted by expert neurophysiologists. This simplified montage could be implemented as part of a multimodal evaluation for bedside prognostication.

To evaluate the cardiovascular risk (CVR) and analyze its relationship with detection of early carotid artery atherosclerotic lesion in patients with rheumatoid arthritis (RA).One hundred and nine RA patients aged 45 to 60 without established cardiovascular diseases (CVD) were included in the study. The median age was 52 [48; 54] years, duration of RA was 120 [36; 204] months, DAS28 was 4.7 [3.5; 5.6] points. CVD risk was calculated with mSCORE, Reynolds Risk Score (RRS), ASSIGN, QRISK3, ERS-RA scales and Carotid Artery Doppler Ultrasound Exam was performed for all patients.High risk was found in 5, 5, 14, 6, and 38% of patients according to mSCORE, RRS, ASSIGN, QRISK3, ERS-RA scales, respectively. Atherosclerotic plaques of carotid arteries were found in 30% of patients. It was found that carotid intima-media thickness is correlated to all CVR calculators, age, systolic and diastolic blood pressure, cholesterol, erythrocyte sedimentation rate, interleukin-6 levels. The sensitivity and specificity of the CVR algorithms in prognostication of atherosclerotic carotid artery lesions were 73 and 67% for mSCORE, 64 and 63% for RRS, 64 and 56% for ASSIGN, 73 and 49% for QRISK3, respectively, p0.05 in all cases, 67 and 50% for ERS-RA, p=0.06.RRS, mSCORE, ASSIGN, QRISK3 calculators equally predict atherosclerotic carotid artery damage in RA patients. The optimal ratio of specificity and sensitivity is shown for the mSCORE scale. Stratification of CVR in RA patients should include assessment of the carotid intima-media thickness. To identify CVR in RA patients, the most informative methods are mSCORE calculation and carotid intima-media thickness determination.Цель. Оценить сердечно-сосудистый риск (ССР) и проанализировать его связь с выявлением раннего атеросклеротического поражения сонных артерий у больных ревматоидным артритом (РА). Материалы и методы. В исследование включены 109 пациентов с РА в возрасте от 45 до 60 лет без установленных сердечно-сосудистых заболеваний (ССЗ). Медиана возраста составила 52 [48; 54] года, продолжительности РА 120 [36; 204] мес; DAS28 4,7 [3,5; 5,6] балла. Пациентам определен суммарный ССР по шкалам mSCORE, Reynolds Risk Score (RRS), ASSIGN, QRISK3, ERS-RА, и выполнена ультразвуковая допплерография сонных артерий. Результаты. По результатам расчета ССР по шкалам mSCORE, RRS, ASSIGN, QRISK3, ERS-RA высокий риск обнаружен у 5, 5, 14, 6 и 38% больных соответственно. У 30% больных выявлены атеросклеротические бляшки сонных артерий. Продемонстрирована связь толщины комплекса интимамедиа (КИМ) сонных артерий со всеми калькуляторами ССР, а также с возрастом, показателями систолического и диастолического артериального давления, уровнями холестерина, скорости оседания эритроцитов, интерлейкина-6. Чувствительность и специфичность алгоритмов ССР в прогнозировании атеросклеротического поражения сонных артерий составили для mSCORE 73 и 67%, для RRS 64 и 63%, для ASSIGN 64 и 56%, для QRISK3 73 и 49% соответственно, р0,05 во всех случаях, для ERS-RА 67 и 50%, р=0,06. Заключение. Калькуляторы mSCORE, RRS, ASSIGN, QRISK3 в равной степени прогнозируют атеросклеротическое поражение сонных артерий у больных РА. Оптимальное соотношение специфичности и чувствительности показано для шкалы mSCORE. Стратификация риска ССЗ у больных РА должна включать оценку толщины КИМ сонных артерий. Для идентификации риска развития ССЗ у больных РА наиболее информативными являются вычисление mSCORE и определение толщины КИМ сонных артерий.

The article highlights the current status of symptomatic slow-acting drugs (SYSADOA) in osteoarthritis (OA). Mechanism of action, clinical studies data on the effectiveness of glucosamine (GA) and chondroitin sulfate (CS) and their combinations in OA, their positive symptomatic and structural-modifying effects, are described. The article provides the latest recommendations for the OA treatment with these two drugs and presents an argument for the combination therapy with both drugs as a background therapy in the earliest stages of OA. It is indicated that such therapy should be long-term due to its high safety and possible reduction of cardiovascular accidents risk as well. It is noted that therapeutic doses of CS and GA are ≥1500 and ≥800 mg per day, respectively, and encapsulated forms of SYSADOAs have advantages due to their pharmacokinetic features.

While most guidelines still recommend colorectal cancer (CRC) screening initiation at age 50 years in average-risk individuals, guideline-creating bodies are starting to lower the recommended age of initiation to 45 years to mitigate the trend of increasing CRC rates in younger populations. Using CRC-AIM, we modeled the impact of lowering the CRC screening initiation age, incorporating theoretical and reported adherence rates, for triennial multi-target stool DNA (mt-sDNA) or annual fecal immunochemical test (FIT) screening.Screening strategies were simulated for individuals without CRC at age 40 and screened from ages 50 to 75 or 45 to 75 years. Outcomes included CRC incidence, CRC mortality, and life-years gained (LYG) per 1000 individuals screened (compared with no screening). Models used theoretically perfect (100%) and previously reported (71% mt-sDNA; 43% FIT) adherence rates.With perfect adherence, mt-sDNA and FIT resulted in 22.2 and 23.4 more predicted LYG, respectively, with screening initiation at age 45 versus 50 years; reported adherence resulted in 23.9 and 24.4 more LYG, respectively. With perfect adherence, screening initiation at age 45 versus 50 years resulted in 26.1 and 28.6 CRC cases, respectively, with mt-sDNA and 22.8 and 25.5 cases with FIT; with reported real-world adherence there were 28.5 and 31.2 cases, respectively, with mt-sDNA and 37.1 and 40.2 cases with FIT. Similar patterns were observed for CRC deaths. With screening initiation at age 45 and reported adherence, mt-sDNA averted 8.6 more CRC cases and 3.3 more deaths per 1000 individuals than FIT.Estimated CRC screening outcomes improved by lowering the initiation age from 50 to 45 years. Incorporating reported adherence rates yields greater benefits from triennial mt-sDNA versus annual FIT screening.

Intimate partner violence against women (IPVAW) is a global public health issue often assumed to be associated with gender inequality. The so-called Nordic Paradox, the apparently contradictory co-existence of high levels of IPVAW and of gender equality in Nordic countries, has not been adequately explained. This study explores discussions about how this apparent paradox can be understood among 30 IPVAW professionals working in southern Sweden, through a thematic analysis of focus groups and individual and paired interviews. The analysis highlights complexities of gender (in)equality and its links with IPVAW in Sweden, of relevance for the addressing and prevention of IPVAW.

Antibiotic resistance (ABR) has been identified as a critical threat to global health at the highest policy fora. A leading cause of ABR is the inappropriate use of antibiotics by both patients and healthcare providers. Although countries around the world have committed to developing and implementing national action plans to tackle ABR, there is a considerable gap in evidence about effective behaviour change interventions addressing inappropriate use of antibiotics in low- and middle-income countries (LMICs), where ABR is growing at an alarming rate. We conducted a systematic review to synthesize evidence about the effectiveness and cost-effectiveness of behaviour change interventions to reduce inappropriate use of antibiotics in LMICs. Three databases were searched using a set of predefined search terms and exclusion criteria. The search identified 43 relevant articles. A narrative synthesis of results was conducted using the Behaviour Change Wheel framework to categorize intervention components. The majority of the reviewed studies were set in lower-middle-income or low-income countries located in Sub-Saharan Africa or East Asia and the Pacific. Twenty-four articles evaluated multi-faceted interventions over a period of 12 months or less. Despite the widespread use of antibiotics in the community, interventions were primarily implemented in public health facilities, targeting health professionals such as doctors, nurses, and other allied medical staff. Although education for providers was the most widely used strategy for influencing antibiotic use, it was shown to be most effective when used in conjunction with training or other enabling and supportive measures to nudge behaviour. Six articles included an evaluation of costs of interventions and found a reduction in costs in inpatient and outpatient settings, and one article found a training and guidelines implementation-based intervention to be highly cost-effective. However, the small number of articles conducting an economic evaluation highlights the need for such analyses to be conducted more frequently to support priority setting in resource-constrained environments.

Objective: analysis of the osteoarthritis (OA) comorbidity taking into account the microelement status and genetic polymorphisms of the examined patients, determination of the prospects for the OA prevention and therapy.Material and methods. A cross-sectional study of a multiethnic cohort (n=655, mean age 43±14 years, 95% CI 29–70) formed on the basis of the Institute of Microelements database, was carried out. For all participants, the content of the 62 elements of the Element Periodic Table profile in hair was identified and variants of 120 nucleotide polymorphisms associated with various pathologies were definedResults. The study found that 18 of the 27 ICD-10 diagnoses examined were comorbid with OA. Osteoarthritis was comorbid with pathologies with a pronounced component of inflammation (ulcerative colitis, atherosclerosis, unspecified encephalopathy, obesity, diabetes mellitus, essential (primary) hypertension, urine calculus, acute myocardial infarction, cholelithiasis, etc.). The core of OA comorbidity was established, which included following pathologies: chronic cerebral ischemia, diabetes mellitus, thrombophlebitis, atherosclerosis, cholelithiasis. Seven profiles of the most frequent combinations of these diagnoses were identified. The presence of 2 out of 5 of these pathologies was recorded in 92% of patients with OA (n=50) and only in 2% of control patients (n=600), which corresponded to an extreme increase in the risk of OA (OR 56.3, 95% CI 17.4–181.6, pConclusion. Based on the obtained results the prospects for the use of chondroitin sulfate and glucosamine sulfate in patients with an increased risk of OA development are shown.

Objective: to evaluate changes in T- and B-lymphocyte subpopulations at different stages of rheumatoid arthritis (RA).Patients and methods. The study included 53 patients with a definite RA diagnosis according to the 2010 ACR/EULAR criteria (mean age 54.2 [47; 62] years). Group 1 included 27 patients (25 women and 2 men) without history of synthetic disease modifying anti-rheumatic drugs (sDMARDs) intake, group 2 included 26 patients (22 women and 4 men) receiving sDMARDs (methotrexate or leflunomide). The control group consisted of 29 healthy volunteers (23 women and 6 men), the median age was 58.5 [53; 62] years. In all participants flow cytofluorometry according to the standard technique with immunophenotyping of T- and B-lymphocytes was performed.Results and discussion. Compared to controls, patients in group 1 who had not previously received sDMARDs showed a transient increase in "switched" memory B-cells, transient B-cells, and plasmablasts, which was not observed in patients of group 2 (on sDMARDs therapy). Patients with advanced RA showed a statistically significant decrease in the absolute and relative number of memory B-cells, the absolute and relative number of "switched" B-lymphocytes, as well as the number of plasmablasts and transient cells. In RA patients, a statistically significant rela tionship was established between the number of swollen joints and the level of plasmablasts (r=0.51), memory cells (r=0.54), and "switched" B-cells (r=0.41), p< 0,05 in all cases. There were no statistically significant changes in other subpopulations of B-lymphocytes and the profile of T-lymphocytes.Conclusion. Changes in the B-lymphocyte profile are characteristic of different stages of RA. At an early stage, there is an increase in the number of transient B-lymphocytes, plasmablasts and plasmocytes, and in the advanced stage, a decrease in the level of certain populations of B-lymphocytes, such as memory B-cells and "switched" B-lymphocytes. It can be assumed that the ineffectiveness of sDMARDs is associated with a change in the population composition of B-lymphocytes, which requires further study.

Rebecca Perrain,1,2 David Calvet,3– 5 Vincent Guiraud,3– 5 Lila Mekaoui,1 Jean-Louis Mas,3– 5 Philip Gorwood1,2,5 1GHU Paris Psychiatrie et Neurosciences, CMME, Hôpital Sainte-Anne, Paris, France; 2University of Paris, Paris, France; 3GHU Paris Psychiatrie et Neurosciences, Department of Neurology, Hôpital Sainte-Anne, Paris, France; 4University of Paris, FHU Neurovasc, Paris, France; 5Institute of Psychiatry and Neuroscience of Paris, INSERMU1266, Paris, FranceCorrespondence: Rebecca PerrainClinique des Maladies Mentales et de l’Encéphale, Sainte-Anne Hospital, GHU Paris– Psychiatrie & Neurosciences, 100 rue de la Santé 75674 Paris Cedex 14, Paris, FranceTel +33 1 45 65 83 64Fax +33 1 45 65 76 56Email r.perrain@ghu-paris.frPurpose: Post-stroke depression (PSD) affects one third of stroke survivors, with multiple severe negative consequences. We aim to assess the weight of four different types of clinical risk factors for PSD.Patients and Methods: We conducted a prospective cohort study in a stroke centre. After stroke, patients were assessed for cognitive performances, psychiatric standardized questionnaires and socio-demographic features. They were called three months after and assessed for major depressive episode using DSM criteria.Results: PSD was diagnosed in 8 of the 59 (13.6%) patients enrolled in the study. After multivariate analysis, only “previous history of depressive episode” remained a significant predictive factor for PSD, the model explaining 19% of the total variance (OR=18.0; p=0.002). Patients with a previous history of depression had a 10-fold increased risk for PSD.Conclusion: Previous history of depression is confirmed as a strong risk factor for PDS and allow the identification of an at-risk sub-group of patients.Keywords: post-stroke depression, depression, stroke, risk factors, prevention, cohort