Secondary Criteria Research Articles

Searching for Biomarkers in the Blood of Patients at Risk of Developing Parkinson's Disease at the Prodromal Stage.

Parkinson's disease (PD) is diagnosed many years after its onset, under a significant degradation of the nigrostriatal dopaminergic system, responsible for the regulation of motor function. This explains the low effectiveness of the treatment of patients. Therefore, one of the highest priorities in neurology is the development of the early (preclinical) diagnosis of PD. The aim of this study was to search for changes in the blood of patients at risk of developing PD, which are considered potential diagnostic biomarkers. Out of 1835 patients, 26 patients were included in the risk group and 20 patients in the control group. The primary criteria for inclusion in a risk group were the impairment of sleep behavior disorder and sense of smell, and the secondary criteria were neurological and mental disorders. In patients at risk and in controls, the composition of plasma and the expression of genes of interest in lymphocytes were assessed by 27 indicators. The main changes that we found in plasma include a decrease in the concentrations of l-3,4-dihydroxyphenylalanine (L-DOPA) and urates, as well as the expressions of some types of microRNA, and an increase in the total oxidative status. In turn, in the lymphocytes of patients at risk, an increase in the expression of the DA D3 receptor gene and the lymphocyte activation gene 3 (LAG3), as well as a decrease in the expression of the Protein deglycase DJ-1 gene (PARK7), were observed. The blood changes we found in patients at risk are considered candidates for diagnostic biomarkers at the prodromal stage of PD.

'Traffic light' theory for Covid-19 spatial mitigation policy design

We suggest the use of outdegrees from graph theory to rank locations in terms of their contagiousness. We show that outdegrees are equal to the column sums of spatial autoregressive matrices, which may be estimated using econometric methods for spatial panel data. In contrast to outdegree, R is invalid for 'traffic light' shading because it fails to distinguish between the export and import of contagion between sub-national locations. Simulation methods are used to illustrate the concept of outdegrees and its structural determinants in terms of centrality, indigenous contagion and spatial contagion. An empirical illustration is presented for Israel. A secondary criterion for traffic light shading involves the stochastic structure of morbidity shocks, which induce 'spiking' through their autoregressive persistence, conditional heteroscedasticity and diffusion jump parameters.

Arthroscopic approach in initial training: Study of a novice cohort using inverse direct and indirect approaches and its implication in the development of training programs

IntroductionArthroscopic training includes successive stages of observation, reproduction and then repetition. Learning through simulation in 2D virtual reality makes it possible to repeat these different stages to enhance the learner's experience in complete safety and a shorter timeframe. Some procedures require inversion of the optical and instrumental approaches in the axial plane, disrupting the existing psychomotor and technical skills. The objective of this study was to compare the degree of difficulty and the distribution of results for the same exercise carried out alternately in classical holding and inverted holding of the instruments in a cohort of novice learners. Materials and methodsTwenty-two medical students, novices in arthroscopic surgery, participated in the study. Each performed an exercise consisting of grasping ten targets with arthroscopic forceps and placing them in a basket on the VirtaMed ArthroS™ simulator. The exercise was performed with the scope and grasping instrument pointed away from the operator, “catch the stars front” (CTSF), then directed towards the operator, “catch the stars back” (CTSB). The simulator recorded several parameters making up an overall composite score (“overall performance score”, OPS) out of 120 points. Voluntary abandonment of the exercise was also collected. ResultsAll students completed the CTSF exercise but 6 dropped out of the CTSB exercise (27%, p=0.01). In the CTSF exercise, the average OPS was higher with 45.9 points versus 22.8 points in the CTSB exercise (p<0.001). By detailing the components of the OPS score, the parameters of interest on the Fundamentals of Arthroscopic Training (FAST) module of the simulator included: the distance traveled by the scope and the grasping forceps was significantly greater in the CTSB group (p<0.001), the duration of the exercise was significantly greater in the CTSB group (p<0.001), the time spent with the instruments in the videoscopic field was significantly lower in the CTSB group (p=0.001) and finally the absence of a significant difference in the camera alignment compared to the horizontal plane between the two groups. ConclusionThe exercise with the instruments directed towards the operator is more difficult with a greater distribution for all the secondary criteria except for the camera alignment, which suggests that it could be more discriminating. The dropout rate is also higher. It would therefore be interesting to introduce CTSB type training in initial training programs in arthroscopy. Level of evidenceIII, comparative prospective study.

No difference in outcomes between large- and small-pore meshes in a prospective, randomized, multicenter trial investigating open retromuscular meshplasty for incisional hernia repair

Study designA randomized, controlled, prospective multicenter clinical trial with a parallel group design was initiated in eight surgical centers to compare a large-pore polypropylene mesh (Ultrapro®) to a small-pore polypropylene mesh (Premilene®) within a standardized retromuscular meshplasty for incisional hernia repair.MethodsBetween 2004 and 2006, patients with a fascial defect with a minimum diameter of 4 cm after vertical midline laparotomy were recruited for the trial. Patients underwent retromuscular meshplasty with either a large-pore or a small-pore mesh to identify the superiority of the large-pore mesh. Follow-up visits were scheduled at 5 and 21 days and 4, 12, and 24 months after surgery. A clinical examination, a modified short form 36 (SF-36®), a daily activity questionnaire, and an ultrasound investigation of the abdominal wall were completed at every follow-up visit. The primary outcome criterion was foreign body sensation at the 12-month visit, and the secondary endpoint criteria were the occurrence of hematoma, seroma, and chronic pain within 24 months postoperatively.ResultsIn 8 centers, 181 patients were included in the study. Neither foreign body sensation within the first year after surgery (27.5% Ultrapro®, 32.2% Premilene®) nor the time until the first occurrence of foreign body sensation within the first year was significantly different between the groups. Regarding the secondary endpoints, no significant differences could be observed. At the 2-year follow-up, recurrences occurred in 5 Ultrapro® patients (5.5%) and 4 Premilene® patients (4.4%).ConclusionDespite considerable differences in theoretical and experimental works, we have not been able to identify differences in surgical or patient-reported outcomes between the use of large- and small-pore meshes for retromuscular incisional hernia repair.Trial registrationClinical Trials NCT04961346 (16.06.2021) retrospectively registered.

Analytical Investigation of the Effects of Secondary Structural Members on the Structural Behaviors of Transmission Towers

High-voltage transmission towers consist of structures that are designed to avoid the risk of electric shock and prevent the risk of collapse. Hence, for efficiency, they are generally designed as high-rise towers. The main tower posts are the primary structural members that resist loads under various load conditions. Therefore, the contribution of the secondary members to securing the stiffness and strength of the main posts by reducing the effective buckling length is an important one. However, we lack detailed secondary member design criteria. In this study, we observed the structural effects of the horizontal members and braces on the torsional stiffness, elastic buckling strength, and load-carrying capacity of a transmission tower using various structural analysis methods, including linear elastic, eigenvalue, and geometric nonlinear and inelastic analyses, under governing load combinations. According to the analytical results, it is the brace spacing rather than the horizontal members that substantially affects the structural performance. Therefore, we can minimize the number of horizontal members if we erect sufficient brace members. If the brace spacing is wide, then the horizontal members should be erected to create K bracing, thereby enhancing the buckling resistance of the main posts.

A Minimal Metaphysics for Scientific Practice

<i>A Minimal Metaphysics for Scientific Practice</i>

Field efficacy and safety of Felpreva® (tigolaner, emodepside and praziquantel) spot-on for the treatment of natural ear mite infestations (Otodectes cynotis) and notoedric mange (Notoedres cati) in cats

The miticide efficacy of a single treatment with Felpreva® (tigolaner, emodepside and praziquantel) spot-on solution for cats was evaluated in two European field studies. One study was conducted in cats naturally infested with Otodectes cynotis. The other study was conducted in cats naturally infested with Notoedres cati. In both studies, the presence of viable mites was confirmed prior to treatment (Day -1/Day 0) and re-evaluated on Day 14 (O. cynotis study) and on Day 28 (both studies). Efficacy was calculated based on the number of viable mites found after treatment. In the O. cynotis study, the primary criterion was the percentage of mite-free cats after treatment with Felpreva® compared to a sarolaner/selamectin combination (Stronghold® Plus, Zoetis) as a positive control. In the N. cati study, the primary criterion was the difference between arithmetic mean mite counts of cats treated with Felpreva® and cats treated with a placebo formulation (solketal). Secondary criteria in both studies were changes in clinical lesion scores after treatment. In both studies, all Felpreva®-treated cats were mite-free (100% parasitological cure) on Day 28, 4 weeks after treatment. Signs of mange on Day 28 were clinically improved in all O. cynotis-infested cats (100%) and clinically cured in all N. cati-infested cats (100%). There were no records of any adverse events or application site reactions in Felpreva®-treated cats.

Luarea deciziilor terapeutice în carcinomul cu celule Merkel – punctul de vedere al chirurgului oncolog

Introduction. Merkel cell carcinoma (MCC) is not as well-known as other malignant skin tumors, although it has been found to have a higher mortality rate than malignant melanoma, estimated at 30%. This poor prognosis is due to its aggressiveness characterized by an increased risk of recurrence, both regional and at distance. Materials and method. We conducted a literature review over the past five years, from January 2017 to September 2022, looking for relevant publications in the PubMed database, on Merkel cell carcinoma, or cutaneous neuroendocrine cancer, or trabecular skin cancer, as it is also known in literature, since 1972, when Toker first introduced the term. A total of 799 results were identified at the initial search in the database, which is why we added another secondary selection criterion by entering the terms “treatment” and “surgical excision”. In the end, 44 articles were analyzed, relevant for the surgical stage of the treatment and for its classification in multimodal treatment, excluding those that were not written in English. In addition, articles from the bibliographic indices were selected and consulted. Results. Six retrospective studies were selected, which ana­lyze the role of adjuvant radiation therapy, complete lymph node dissection (CLND) or both procedures in patients with positive sentinel lymph node biopsy (SNLB). Conclusions. Surgery is the basic treatment, and the earlier it is applied by the first curative intention, the better the rest of the mul­ti­mo­dal treatments manage to control the tumor evo­lu­tion. Radiation therapy as a single therapy has not led to satis­factory results, even though Merkel cell carcinoma is highly radiosensitive, and will be considered only in ad­di­tion to surgery.

Technical Performance Assessment and Quality Control of Ultrasound Device Monitors.

The purpose of this study was to investigate and evaluate the current technical performance of ultrasound imaging device displays. Altogether 53 ultrasound device displays were evaluated in two hospital districts of Finland. The performance of the displays was evaluated with tests and test patterns developed by American Association of Physicists in Medicine (AAPM). Minimum, maximum and ambient luminances (Lmin,Lmax,Lamb) were measured. Ambient ratio (AR), luminance ratio (LR), [Formula: see text] and [Formula: see text] were calculated, and luminance uniformity, defined as deviation from the median (MLD), was evaluated. The results indicate that none of the measured displays fulfill the AAPM Task Group (TG) 270 maximum luminance recommendation for diagnostic displays. A majority (32/53, 60%) of the displays fail the AAPM TG270 acceptable level for secondary displays as well. Only 3 of 53 (6%) displays were at the acceptable level for diagnostic displays. Also, for most of the displays (41/53, 77%), [Formula: see text] was under the diagnostic acceptable level. Ambient ratios exceeded the acceptable limit in 31 of 53 (58%) displays. Luminance ratios, on the other hand, were within acceptable levels for the majority of displays (38/53, 72%). All devices passed the AAPM requirement for luminance uniformity (MLD). The results indicate that the maximum luminance and minimum luminance of most displays are not sufficient. AAPM, the Society for Imaging Informatics in Medicine and the American College of Radiology introduced the updated luminance [Formula: see text] and [Formula: see text] criteria in 2012. All ultrasound displays should at least fulfill the AAPM TG18 secondary display minimum criteria. Even so, 6 of 53 (11%) fail. The newest displays should be expected to fulfill the revised AAPM TG270 criteria as well. Display technology has developed, and therefore, monitor testing needs to be updated.

CONSTRUCTION SYSTEM SELECTION IN LOW-BED CAPACITY HEALTH BUILDINGS WITH FUZZY AHP IN EARTHQUAKE ZONES

Purpose: Reconstruction of health buildings that were heavily damaged after the earthquake has become an important issue in Turkey. The negative performance of the construction systems of health buildings after major earthquakes necessitates the evaluation of the building system (CS) options, which can create an alternative to the market, according to various criteria. The main purpose of the study is to develop a systematic basis for the CS of 1816 health institutions to be rebuilt within the scope of the UDSEP 2023 project and to decide between alternatives in Turkey. In this study, the example of a hospital with a low bed capacity (20 beds) was discussed. Method: In the application of the Methodology-Fuzzy Analytical Hierarchy Process (FAHP) method of the research, 40 expert opinions were taken at the stages of planning, construction and inspection of health buildings. Findings: Experts in various fields of the construction industry have determined that CS performance is the primary criterion and cost is the secondary criterion for healthcare buildings in high seismic hazard areas. Conclusion: Among the CS alternatives, Structural Steel Frame (SSF) was determined as the most suitable structural system for earthquake zones.

KRITERIA KRIMINALISASI: ANALISIS PEMIKIRAN MOELJATNO, SUDARTO, THEO DE ROOS, DAN IRIS HAENEN

In criminal law, “criminalization” is defined as a process of determining certain conduct as a criminal offense through legislation. This doctrinal legal research article describes and analyzes the criteria for criminalization as promulgated by Moeljatno, Sudarto, Theo de Roos, and Iris Haenen. Moeljatno’s criteria are: 1) the conduct is harmful to the public, 2) criminalization is the primary means to deter the harmful conduct, and 3) the government’s ability to effectively enforce the criminal provision. Sudarto promulgates three criteria: 1) harmfulness of the conduct, 2) cost and benefit analysis, and 3) law enforcement burden. Furthermore, Theo de Roos’ six criteria are: 1) feasibility and motivation of harm, 2) tolerance, 3) subsidiarity, 4) proportionality, 5) legality, and 6) practical applicability and effectiveness. Lastly, based on de Roos’ typology Iris Haenen formulates three criteria: 1) primary criteria, which contains “threshold principles”: the conduct must be a) harmful and b) wrongful, 2) secondary criteria, which contains “moderating principles”: proportionality, subsidiarity, and effectiveness, and 3) legality criterion (lex certa). The criteria for criminalization can be employed by the legislators and general public in scrutinizing the feasibility of criminalization of a conduct, to ensure that only the conducts which meet all the criteria that can be criminalized. Only by doing so will the practice of criminalization adhere to the ultimum remedium principle and deter unnecessary criminalization and overcriminalization.

Validity and repeatability of cardiopulmonary exercise testing in interstitial lung disease

BackgroundCardiopulmonary exercise testing (CPET), and its primary outcome of peak oxygen uptake (VO2peak), are acknowledged as biomarkers in the diagnostic and prognostic management of interstitial lung disease (ILD). However, the validity and repeatability of CPET in those with ILD has yet to be fully characterised, and this study fills this evidence gap.MethodsTwenty-six people with ILD were recruited, and 21 successfully completed three CPETs. Of these, 17 completed two valid CPETs within a 3-month window, and 11 completed two valid CPETs within a 6-month window. Technical standards from the European Respiratory Society established validity, and repeatability was determined using mean change, intraclass correlation coefficient and typical error.ResultsEvery participant (100%) who successfully exercised to volitional exhaustion produced a maximal, and therefore valid, CPET. Approximately 20% of participants presented with a plateau in VO2, the primary criteria for establishing a maximal effort. The majority of participants otherwise presented with secondary criteria of respiratory exchange ratios in excess of 1.05, and maximal heart rates in excess of their predicted values. Repeatability analyses identified that the typical error (expressed as percent of coefficient of variation) was 20% over 3-months in those reaching volitional exhaustion.ConclusionThis work has, for the first time, fully characterised how patients with ILD respond to CPET in terms of primary and secondary verification criteria, and generated novel repeatability data that will prove useful in the assessment of disease progression, and future evaluation of therapeutic regimens where VO2peak is used as an outcome measure.

Feasibility and Short-Term Effects of Low-Threshold Opioid Substitution Treatment during the COVID-19 Pandemic in Hamburg, Germany

Introduction: After rapidly opening up a low-threshold clinic to support heavily opioid-dependent persons at the beginning of the COVID-19 pandemic in April 2020 in Hamburg (Germany), this non-interventional study evaluated the feasibility and short-term effects of opioid substitution treatment (OST). The low-threshold concept was customized for the pandemic situation and is the first of its kind in Germany. Methods: Patients who had already begun treatment were questioned in two assessments, at T1 shortly after beginning treatment and at T2 6 months later. The primary outcome criterion was their quality of life using the OSTQOL. Secondary criteria included retention rate, their mental and physical health (measured by the BSI-18 and the OTI Health Scale), social situation, drug use, COVID-19 status, and satisfaction with treatment. Results: Out of 84 patients included in the study, 51 participated in both assessments, resulting in a 6-month retention rate of 60.7%. 27.5% were females, and 72.5% were males. The feasibility question of the low-threshold OST clinic can clearly be answered positively. During the course of the study over 6 months, the situation mainly remained stable regarding quality of life, physical and mental health, and days of drug consumption. Patients significantly reduced the time they spent on the drug scene from 8.5 (SD = 7.56) to 6.1 (SD = 6.71) hours a day between the beginning of OST and T2 (p = 0.020). While 56.9% answered to be homeless at the beginning of OST, only 33.3% answered not to have found an accommodation by T2 (p = 0.012). The number of patients having contact to social workers increased from 51.0% to 74.5% (p = 0.004). Almost 2 fifths of the patients took part in PCR testing for COVID-19 (that only being done if they had symptoms), and none of the tests were positive. Discussion/Conclusions: Overall, the low-threshold OST clinic has been successfully implemented in order to help a vulnerable group of people navigate through a global pandemic and support the public health sector. Further conclusions on effects are limited by the short study period and the small number of patients, which calls for further research studies in a larger setting.

Gait analysis after total hip arthroplasty by direct minimally invasive anterolateral approach: A controlled study

IntroductionClinical and functional improvement after minimally invasive total hip arthroplasty (THA) has become increasingly controversial. The minimally invasive anterolateral approach (MIALA) allows rapid recovery resulting in a reduced need for rehabilitation. Alterations in muscle and static balance have previously been demonstrated. Results in the context of quantified gait analysis (QGA) and MIALA compared to an asymptomatic population remain unknown beyond one year postoperatively. Thus, the main objective of this controlled study was to compare the spatiotemporal parameters of gait, obtained using a QGA, beyond one year postoperatively in subjects operated on for THA by MIALA, with a group of asymptomatic subjects of the same age. The secondary objectives of the study were to compare the other QGA and EMG data acquired in operated subjects with asymptomatic subjects. HypothesisWe hypothesized that QGA and EMG parameters would not normalize beyond one year postoperatively. Patients and methodsThirty-one subjects were recruited, including 16 patients (68 years old; IQR: 65–70) who underwent MIALA, at 15.5 months postoperatively (IQR: 13–17) and 15 asymptomatic subjects (62 years old; IQR: 61–71). Subjects underwent QGA and maximal isometric muscle force tests on the gluteus medius, gluteus maximus, Tensor Fascia Lata (TFL) and Sartorius muscles. Spatiotemporal gait parameters were the primary endpoint. The other QGA parameters: kinetics (characteristic values of vertical ground reaction forces, peak hip moments) and kinematics (hip joint amplitudes and pelvic mobility in the frontal and sagittal plane) constituted the secondary criteria. ResultsFive subjects were excluded for unrestored offset. Walking speed was lower in operated patients (1.03m/s versus 1.18m/s, p=0.005). Maximal isometric muscle force moments were lower in patients operated on for the gluteus maximus and medius as well as the TFL (p<0.005). The vertical ground reaction forces were lower for the operated patients for the loading phase (FzFCmax, p=0.001), the single stance phase (FzSPmin, p=5.05.10−2) and the swing phase (FzTOmax, p=0.0002). The moments were lower in the sagittal plane for the operated patients (0.6N.m for the operated versus 1.1N.m for the asymptomatic, p=0.02). The pelvic amplitudes in the sagittal plane were lower for operated patients (3.3° versus 7.2°, p=0.05). DiscussionOur hypothesis appears to be validated. Gait deficits persisted beyond one year postoperatively after THA with MIALA. A decrease in walking speed, maximal isometric muscle force of the gluteus medius and gluteus maximus and TFL was observed, as well as a decrease in propulsive force and peak hip moment. Functionally, these results could signify muscle damage following surgery, requiring rehabilitation for improved muscle function. Level of proofIII: Non-randomized controlled trial.

Impact of Sarcopenia on Patients with Localized Pancreatic Ductal Adenocarcinoma Receiving FOLFIRINOX or Gemcitabine as Adjuvant Chemotherapy.

Despite its toxicity, modified FOLFIRINOX is the main chemotherapy for localized, operable pancreatic adenocarcinomas. Sarcopenia is known as a factor in lower overall survival (OS). The purpose of this study was to assess the impact of sarcopenia on OS in patients with localized pancreatic ductal adenocarcinoma (PDAC) who received modified FOLFIRINOX or gemcitabine as adjuvant chemotherapy. Patients with operated PDAC who received gemcitabine-based (GEM group) or oxaliplatin-based (OXA group) adjuvant chemotherapy between 2008 and 2021 were retrospectively included. Sarcopenia was estimated on a baseline computed tomography (CT) examination using the skeletal muscular index (SMI). The primary evaluation criterion was OS. Secondary evaluation criteria were disease-free survival (DFS) and toxicity. Seventy patients treated with gemcitabine-based (n = 49) and oxaliplatin-based (n = 21) chemotherapy were included, with a total of fifteen sarcopenic patients (eight in the GEM group and seven in the OXA group). The median OS was shorter in sarcopenic patients (25 months) compared to non-sarcopenic patients (158 months) (p = 0.01). A longer OS was observed in GEM non-sarcopenic patients (158 months) compared to OXA sarcopenic patients (14.4 months) (p &lt; 0.01). The median OS was 157.7 months in the GEM group vs. 34.1 months in the OXA group (p = 0.13). No differences in median DFS were found between the GEM group and OXA group. More toxicity events were observed in the OXA group (50%) than in the GEM group (10%), including vomiting (p = 0.02), mucositis (p = 0.01) and neuropathy (p = 0.01). Sarcopenia is associated with a worse prognosis in patients with localized operated PDAC whatever the delivered adjuvant chemotherapy.

Defining working time versus rest time: An analysis of the recent CJEU case law on stand-by time

The article explores the evolution of the CJEU jurisprudence following on from the Matzak case. It provides an analysis of the most recent judgments on stand-by time, including those in case C-344/19 Radiotelevizija Slovenija, case C-580/19 Stadt Offenbach am Main, case C-107/19 Dopravní podnik hl. m. Prahy, and case C-214/20 Dublin City Council. The disputes concerned workers on stand-by duty who were not required to be physically present at the location expressly designated by the employer, but were expected to resume work within a short or very short period of time if necessary. In order to classify stand-by periods as working time or rest periods under the Directive 2003/88, the CJEU analyses whether the constraints imposed on the worker are such as to affect, objectively and very significantly, the possibility for the latter freely to manage the time during which his or her professional services are not required and to pursue his or her own interests. Moreover, the CJEU requires that employers cannot establish periods of stand-by time that are so long or so frequent that they constitute a risk to the safety or health of workers, irrespective of those periods being classified as rest periods. In the author's opinion, the required response time is a decisive and most important factor in the assessment. If the reaction period is very short, then in principle the stand-by time constitutes working time. Where the situation is not prima facie clear, additional secondary criteria should be taken into account. The factors that fall within the scope of an employer's managerial competences and pertain to an organisation's operational needs, and also the type of work performed by the worker, are relevant in assessing the legal characterisation of a particular stand-by period. The evaluation should not be affected by factors that remain beyond employer's control, e.g., the location of the workplace, the worker's residence, and distance between them.

Improving working relationships with families in German early childhood interventions home visitors: a quasi-experimental training study

BackgroundHome visitation services within German Early Childhood Interventions (ECI) for families with a child aged 0–3 are mainly provided by frontline pediatric nurses and family midwifes. Home visitors are often challenged by difficult interactions with families. Mentalizing, the ability to understand mental states of oneself and others, is a key skill for building effective working relationships, which in turn positively affect intervention outcomes. The aim of this study was to investigate if a mentalizing skills training offered to home visitors active in German ECI contributes to continued professional development. We investigated, whether the training positively affected the quality of the working relationships with families as well as home visitors’ empathy, self-efficacy, and mentalizing.MethodsTo test the effects of a single day mentalizing skills training on the working relationship in N = 73 ECI home visitors, we used a quasi-experimental design with repeated measures (T0, T1, T2, T3) across seven weeks in order to assess immediate change from baseline (T0) after the training (T2) and stability of changes at follow up (T3). A literature-based intervention was implemented before the training to estimate possible repeated measurement and expectational effects (T1). Primary outcome was the quality of the working relationship experienced by the home visitors. Secondary outcome criteria were empathy, work-related self-efficacy, self-reported and observer-rated mentalizing.ResultsSignificant positive change in the working relationship quality was observed at T2 and at T3. Results on the secondary outcomes were less consistent, with data indicating improvement in empathy and increase on some but not all components of mentalizing.ConclusionsThis study provides preliminary evidence that brief mentalizing skills trainings may be an effective method for continuous professional qualification in frontline ECI home visitors who afterwards, experience better working relationships with families. Thus, training participation may positively impact efficacy and implementation of home visitations in ECI.

The APSY-SED study: protocol of an observational, longitudinal, mixed methods and multicenter study exploring the psychological adjustment of relatives and healthcare providers of patients with cancer with continuous deep sedation until death

BackgroundSince 2016, France is the only country in the World where continuous deep sedation until death (CDSUD) is regulated by law. CDSUD serves as a response to refractory suffering in palliative situations where the patients’ death is expected to occur in the following hours or days. Little is known on the psychological adjustment surrounding a CDSUD procedure for healthcare providers (HCPs) and relatives. Our study aims to gather qualitative and quantitative data on the specific processes behind the psychological adjustment of both relatives and HCPs, after the administration of CDSUD for patients with cancer.MethodsThe APSY-SED study is a prospective, longitudinal, mixed-methods and multicenter study. Recruitment will involve any French-speaking adult cancer patient for who a CDSUD is discussed, their relatives and HCPs. We plan to include 150 patients, 150 relatives, and 50 HCPs. The evaluation criteria of this research are: 1/ Primary criterion: Psychological adjustment of relatives and HCPs 6 and 13 months after the death of the patient with cancer (psychological adjustment = intensity of anxiety, depression and grief reactions, CDSUD-related distress, job satisfaction, Professional Stress and Professional experience). Secondary criteria: a)occurrence of wish for a CDSUD in patients in palliative phase; b)occurrence of wish for hastened death in patients in palliative phase; c)potential predictors of adjustment assessed after the discussion concerning CDSUD as an option and before the setting of the CDSUD; d) Thematic analysis and narrative account of meaning-making process concerning the grief experience.DiscussionThe APSY-SED study will be the first to investigate the psychological adjustment of HCPs and relatives in the context of a CDSUD procedure implemented according to French law. Gathering data on the grief process for relatives can help understand bereavement after CDSUD, and participate in the elaboration of specific tailored interventions to support HCPs and relatives. Empirical findings on CDSUD among patients with cancer in France could be compared with existing data in other countries and with results related to other medical fields where CDSUD is also conducted.Trial registrationThis protocol received the National Registration Number: ID-RCB2021-A03042-39 on 14/12/2021.

A Large-Scale High-Throughput Screen for Modulators of SERCA Activity

The sarco/endoplasmic reticulum Ca-ATPase (SERCA) is a P-type ion pump that transports Ca2+ from the cytosol into the endoplasmic/sarcoplasmic reticulum (ER/SR) in most mammalian cells. It is critically important in muscle, facilitating relaxation and enabling subsequent contraction. Increasing SERCA expression or specific activity can alleviate muscle dysfunction, most notably in the heart, and we seek to develop small-molecule drug candidates that activate SERCA. Therefore, we adapted an NADH-coupled assay, measuring Ca-dependent ATPase activity of SERCA, to high-throughput screening (HTS) format, and screened a 46,000-compound library of diverse chemical scaffolds. This HTS platform yielded numerous hits that reproducibly alter SERCA Ca-ATPase activity, with few false positives. The top 19 activating hits were further tested for effects on both Ca-ATPase and Ca2+ transport, in both cardiac and skeletal SR. Nearly all hits increased Ca2+ uptake in both cardiac and skeletal SR, with some showing isoform specificity. Furthermore, dual analysis of both activities identified compounds with a range of effects on Ca2+-uptake and ATPase, which fit into distinct classifications. Further study will be needed to identify which classifications are best suited for therapeutic use. These results reinforce the need for robust secondary assays and criteria for selection of lead compounds, before undergoing HTS on a larger scale.

WITHDRAWN: Myoinositol supplementation for the prevention of gestational diabetes in at-risk patients. Systematic review and meta-analysis

Gestational diabetes (GD) is associated with an increase in maternal and fetal morbidity. The risk factors involved have been clearly identified but no prevention strategies have yet provided robust evidence of their efficacy. Myoinositol has insulin sensitization properties and is of potential interest in the treatment of the disorder. The aim of this work was to assess the efficacy of myoinositol supplementation during pregnancy to prevent GD in patients with known risk factors. A systematic literature review was performed on studies comparing the effects of myoinositol supplementation and placebo on the occurrence of GD in at-risk pregnant women. The main judgement criterion was diagnosis of GD between 24 and 28 gestational weeks by an oral glucose tolerance test. The secondary judgement criteria were the occurrence of maternal fetal complications and the need to initiate insulin treatment to manage GD. Nine studies were included in the meta-analysis. The results showed a significantly higher risk of GD in patients on placebo than in those receiving myoinositol (RR​=​2.58, CI 95%: 1.68 to 3.97, p​<​0.0001) but wide variations between studies (I2​=​71.94%, p​<​0.001). And the risk of prematurity was significantly greater in the children of mothers on placebo (RR: 2.15, IC 95%: 1.32 to 3.20, p​=​0.002). Myoinositol supplementation taken from the beginning of pregnancy reduces the incidence of GD and could be of interest at a dose of 4​g/day as a prevention strategy for patients with identified risk factors.