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Traumatic events generate some of the most enduring memories, yet little is known about how long-lasting fear memories can be attenuated. In this review, we collect the surprisingly sparse evidence on remote fear memory attenuation from both animal and human research. What is becoming apparent is twofold: although remote fear memories are more resistant to change compared with recent ones, they can nevertheless be attenuated when interventions are targeted toward the period of memory malleability instigated by memory recall, the reconsolidation window. We describe the physiological mechanisms underlying remote reconsolidation-updating approaches and highlight how they can be enhanced through interventions promoting synaptic plasticity. By capitalizing on an intrinsi-cally relevant phase of memory, reconsolidation-updating harbors the potential to permanently alter remote fear memories.

This systematic review aimed to provide an overview of reablement interventions according to the recently published ReAble definition and their effect on Activities of Daily Living (ADL). In addition, the most common and promising features of these reablement interventions were identified. Four electronic bibliographic databases were searched. Articles were included when published between 2002 and 2020, which described a Randomised or Clinical Controlled Trial of a reablement intervention matching the criteria of the ReAble definition, and had ADL functioning as an outcome. Snowball sampling and expert completion were used to detect additional publications. Two researchers screened and extracted the identified articles and assessed methodological quality; discrepancies were resolved by discussion and arbitration by a third researcher. Twenty relevant studies from eight countries were included. Ten of these studies were effective in improving ADL functioning. Identifying promising features was challenging as an equal amount of effective and non-effective interventions were included, content descriptions were often lacking, and study quality was moderate to low. However, there are indications that the use of more diverse interdisciplinary teams, a standardised assessment and goal-setting method and four or more intervention components (i.e. ADL-training, physical and/or functional exercise, education, management of functional disorders) can improve daily functioning. No conclusions could be drawn concerning the effectiveness on ADL functioning. The common elements identified can provide guidance when developing reablement programmes. Intervention protocols and process evaluations should be published more often using reporting guidelines. Collecting additional data from reablement experts could help to unpack the black box of reablement.

Background: Improved treatments for bipolar disorder (BD) are needed. Drug repurposing aims to find novel targets for drugs that have been used for other indications. This study investigated the risk of psychiatric hospitalization associated with use of calcium-channel blockers (CCBs; dihydropyridines, diltiazem, verapamil) and adenosine modulators (allopurinol, dipyridamole) in BD in within-individual design. Methods: Individuals diagnosed with BD (ICD-10: F30-F31) were identified from the inpatient, specialized outpatient, sickness absence, and disability pension registers during 1996-2018 in Finland (N = 60,045). The main outcome was hospitalization due to affective symptoms (ICD-10: F30-F39). Within-individual models in stratified Cox regression were used and adjusted hazard ratios (aHR) with 95 % confidence intervals (CIs) reported. Results: Use of CCBs was associated with a decreased risk of hospitalization due to affective symptoms (aHR 0.83, 95 % CI 0.78-0.88) when all CCBs were analyzed together. Of specific CCBs, use of diltiazem (0.71, 0.55-0.91) and dihydropyridines (0.83, 0.78-0.89) were associated with a decreased risk but verapamil was not (0.93, 0.73-1.19). Use of adenosine modulators in general was associated with a decreased risk of hospitalizations due to affective symptoms (0.87, 0.79-0.96). Both allopurinol (0.85, 0.74-0.97) and dipyridamole (0.89, 0.78-1.00) were associated with a marginally decreased risk. Thiazide diuretic use as a negative control was not associated with the risk of hospitalization due to affective symptoms (0.97, 0.83-1.13). Limitations: Due to the observational nature of this study, causation cannot be confirmed. Conclusions: Dihydropyridines and diltiazem were associated with a decreased risk of psychiatric hospitalization in bipolar disorder. Results for allopurinol and dipyridamole were inconclusive.

Whether older adults need more protein than younger adults is debated. The population reference intake for adults set by the European Food Safety Authority is 0.83 g/kg body weight (BW)/d based primarily on nitrogen balance studies, but the underlying data on health outcomes are outdated. An expert committee of the Health Council of the Netherlands conducted a systematic review (SR) of randomized controlled trials (RCTs) examining the effect of increased protein intake on health outcomes in older adults from the general population with an average habitual protein intake >= 0.8 g/(kg BW center dot d). Exposures were the following: 1) extra protein compared with no protein and 2) extra protein and physical exercise compared with physical exercise. Outcomes included lean body mass, muscle strength, physical performance, bone health, blood pressure, serum glucose and insulin, serum lipids, kidney function, and cognition. Data of >1300 subjects from 18 RCTs were used. Risk of bias was judged as high (n = 9) or "some concerns" (n = 9). In 7 of 18 RCTs, increased protein intake beneficially affected >= 1 of the tested outcome measures of lean body mass. For muscle strength, this applied to 3 of 8 RCTs in the context of physical exercise and in 1 of 7 RCTs without physical exercise. For the other outcomes, = 0.8 g/(kg BW center dot d) elicits health benefits.Statement of Significance: This systematic review provides a comprehensive, transparent, and up-to-date overview of randomized controlled trials that explicitly focus on potential health effects of protein intakes above the nitrogen-balance studies-based population reference intake of 0.8 g/(kg BW center dot d) in older adults from the general population. This review also serves as an additional source of evidence for deriving a recommended protein intake for older adults.

This systematic review aimed to provide an overview of reablement interventions according to the recently published ReAble definition and their effect on Activities of Daily Living (ADL). In addition, the most common and promising features of these reablement interventions were identified. Four electronic bibliographic databases were searched. Articles were included when published between 2002 and 2020, which described a Randomised or Clinical Controlled Trial of a reablement intervention matching the criteria of the ReAble definition, and had ADL functioning as an outcome. Snowball sampling and expert completion were used to detect additional publications. Two researchers screened and extracted the identified articles and assessed methodological quality; discrepancies were resolved by discussion and arbitration by a third researcher. Twenty relevant studies from eight countries were included. Ten of these studies were effective in improving ADL functioning. Identifying promising features was challenging as an equal amount of effective and non-effective interventions were included, content descriptions were often lacking, and study quality was moderate to low. However, there are indications that the use of more diverse interdisciplinary teams, a standardised assessment and goal-setting method and four or more intervention components (i.e. ADL-training, physical and/or functional exercise, education, management of functional disorders) can improve daily functioning. No conclusions could be drawn concerning the effectiveness on ADL functioning. The common elements identified can provide guidance when developing reablement programmes. Intervention protocols and process evaluations should be published more often using reporting guidelines. Collecting additional data from reablement experts could help to unpack the black box of reablement.The online version contains supplementary material available at 10.1007/s10433-022-00693-3.

Background We require high-quality information on the current burden, the types of therapy and resources available, methods of delivery, care pathways and long-term outcomes for people with aphasia. Aim To document and inform international delivery of post-stroke aphasia treatment, to optimise recovery and reintegration of people with aphasia. Methods & Procedures Multi-centre, prospective, non-randomised, open study, employing blinded outcome assessment, where appropriate, including people with post-stroke aphasia, able to attend for 30 minutes during the initial language assessment, at first contact with a speech and language therapist for assessment of aphasia at participating sites. There is no study-mandated intervention. Assessments will occur at baseline (first contact with a speech and language therapist for aphasia assessment), discharge from Speech and Language Therapy (SLT), 6 and 12-months post-stroke. Our primary outcome is changed from baseline in the Amsterdam Nijmegen Everyday Language Test (ANELT/Scenario Test for participants with severe verbal impairments) at 12-months post-stroke. Secondary outcomes at 6 and 12 months include the Therapy Outcome Measure (TOMS), Subjective Index of Physical and Social Outcome (SIPSO), Aphasia Severity Rating Scale (ASRS), Western Aphasia Battery Aphasia Quotient (WAB-AQ), stroke and aphasia quality of life scale (SAQoL-39), European Quality of Life Scale (EQ-5D), lesion description, General Health Questionnaire (GHQ-12), resource use, and satisfaction with therapy provision and success. We will collect demography, clinical data, and therapy content. Routine neuroimaging and medication administration records will be accessed where possible; imaging will be pseudonymised and transferred to a central reading centre. Data will be collected in a central registry. We will describe demography, stroke and aphasia profiles and therapies available. International individual participant data (IPD) meta-analyses will examine treatment responder rates based on minimal detectable change & clinically important changes from baseline for primary and secondary outcomes at 6 and 12 months. Multivariable meta-analyses will examine associations between demography, therapy, medication use and outcomes, considering service characteristics. Where feasible, costs associated with treatment will be reported. Where available, we will detail brain lesion size and site, and examine correlations with SLT and language outcome at 12 months. Conclusion International differences in care, resource utilisation and outcomes will highlight avenues for further aphasia research, promote knowledge sharing and optimise aphasia rehabilitation delivery. IPD meta-analyses will enhance and expand understanding, identifying cost-effective and promising approaches to optimise rehabilitation to benefit people with aphasia.

Objective:To assess prevalence of hernia recurrence, surgical site infection (SSI), seroma, serious complications, and mortality after retro-rectus repair.Summary Background Data:Ventral abdominal wall hernia is a common problem, tied to increasing frailty and obesity of patients undergoing surgery. For noncomplex ventral hernia, retro-rectus (Rives-Stoppa) repair is considered the gold standard treatment. Level-1 evidence confirming this presumed superiority is lacking.Methods:Five databases were searched for studies reporting on retro-rectus repair. Single-armed and comparative randomized and non-randomized studies were included. Outcomes were pooled with mixed-effects, inverse variance or random-effects models.Results:Ninety-three studies representing 12,440 patients undergoing retro-rectus repair were included. Pooled hernia recurrence was estimated at 3.2% [95% confidence interval (CI): 2.2%-4.2%, n = 11,049] after minimally 12months and 4.1%, (95%CI: 2.9%-5.5%, n = 3830) after minimally 24-months. Incidences of SSI and seroma were estimated at respectively 5.2% (95%CI: 4.2%-6.4%, n = 4891) and 5.5% (95%CI: 4.4%-6.8%, n = 3650). Retro-rectus repair was associated with lower recurrence rates compared to onlay repair [odds ratios (OR): 0.27, 95%CI: 0.15-0.51, P < 0.001] and equal recurrence rates compared to intraperitoneal onlay mesh (IPOM) repair (OR: 0.92, 95%CI: 0.75-1.12, P = 0.400). Retro-rectus repair was associated with more SSI than IPOM repair (OR: 1.8, 95%CI: 1.03 -3.14, P = 0.038). Minimally invasive retro-rectus repair displayed low rates of recurrence (1.3%, 95%CI: 0.7%-2.3%, n = 849) and SSI (1.5%, 95%CI: 0.8%-2.8%, n = 982), albeit based on non-randomized studies.Conclusions:Retro-rectus (Rives-Stoppa) repair results in excellent outcomes, superior or similar to other techniques for all outcomes except SSI. The latter rarely occurred, yet less frequently after IPOM repair, which is usually performed by laparoscopy.

Background This systematic review and meta-analysis examined the effectiveness of orthoses for flexible flatfeet in terms of patient-reported outcomes in children and adults. Methods EMBASE, Medline (OvidSP), Web-of-Science, Scopus, CINAHL, Cochrane Central Register of Controlled Clinical Trials, i.e., Cochrane Central and Pubmed were searched to identify relevant studies since their inception up to February 2021. We included randomized controlled trials (RCT) and prospective studies in which patient reported outcomes at baseline and follow-up in an orthoses group were compared with a no orthoses or sham sole group. Methodological quality of the studies was assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) and the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I). A meta-analysis was performed where there were multiple studies with the same outcome measures, which was the case for the Visual Analogue Scale (VAS) for pain in adults. Results In total nine studies were included: four RCT in children (N = 353) and four RCT and one prospective study in adults (N = 268) were included. There was considerable heterogeneity between studies. A meta-analysis demonstrated that pain reduction between baseline and follow-up was significantly larger in the orthoses (N = 167) than in the control groups in adults (N = 157; − 4.76, 95% CI [− 9.46, − 0.06], p0.05). Conclusion Due to heterogeneity in study designs, we cannot conclude that foot orthoses are useful for flexible flatfoot in children and adults. However, based on the meta-analysis orthoses might be useful in decreasing pain in adults. The authors did not receive support from any organization for the submitted work.

Background This systematic review and meta-analysis examined the effectiveness of orthoses for flexible flatfeet in terms of patient-reported outcomes in children and adults. Methods EMBASE, Medline (OvidSP), Web-of-Science, Scopus, CINAHL, Cochrane Central Register of Controlled Clinical Trials, i.e., Cochrane Central and Pubmed were searched to identify relevant studies since their inception up to February 2021. We included randomized controlled trials (RCT) and prospective studies in which patient reported outcomes at baseline and follow-up in an orthoses group were compared with a no orthoses or sham sole group. Methodological quality of the studies was assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) and the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I). A meta-analysis was performed where there were multiple studies with the same outcome measures, which was the case for the Visual Analogue Scale (VAS) for pain in adults. Results In total nine studies were included: four RCT in children (N = 353) and four RCT and one prospective study in adults (N = 268) were included. There was considerable heterogeneity between studies. A meta-analysis demonstrated that pain reduction between baseline and follow-up was significantly larger in the orthoses (N = 167) than in the control groups in adults (N = 157; - 4.76, 95% CI [- 9.46, - 0.06], p0.05). Conclusion Due to heterogeneity in study designs, we cannot conclude that foot orthoses are useful for flexible flatfoot in children and adults. However, based on the meta-analysis orthoses might be useful in decreasing pain in adults. The authors did not receive support from any organization for the submitted work.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for selenium. Systematic reviews of the literature were conducted to identify evidence regarding excess selenium intake and clinical effects and potential biomarkers of effect, risk of chronic diseases and impaired neuropsychological development in humans. Alopecia, as an early observable feature and a well-established adverse effect of excess selenium exposure, is selected as the critical endpoint on which to base a UL for selenium. A lowest-observed-adverse-effect-level (LOAEL) of 330 mu g/day is identified from a large randomised controlled trial in humans (the Selenium and Vitamin E Cancer Prevention Trial (SELECT)), to which an uncertainty factor of 1.3 is applied. A UL of 255 mu g/day is established for adult men and women (including pregnant and lactating women). ULs for children are derived from the UL for adults using allometric scaling (body weight(0.75)). Based on available intake data, adult consumers are unlikely to exceed the UL, except for regular users of food supplements containing high daily doses of selenium or regular consumers of Brazil nuts. No risk has been reported with the current levels of selenium intake in European countries from food (excluding food supplements) in toddlers and children, and selenium intake arising from the natural content of foods does not raise reasons for concern. Selenium-containing supplements in toddlers and children should be used with caution, based on individual needs.

The aim of this study was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the outcomes of short dental implants (≤7mm) versus vertical bone augmentation followed by regular dental implants (>7mm) in the deficient posterior mandible. In total, eight RCTs (six using interpositional sandwich grafting and two using a guided bone regeneration technique) were reported in 17 articles at different time points. In the meta-analysis of the sandwich group, the relative risk (RR) for implant loss at 1year was in favour of short implants (RR 0.41, P=0.02), while no significant difference was found at 3 years (RR 0.65, P=0.43), 5 years (RR 1.08, P=0.86), or 8 years (RR 1.53, P=0.52). The risk of complications was in favour of short implants (RR 0.34, P=0.0002), as was the mean difference in marginal bone resorption after 1 year (-0.09mm, P=0.17), 3 years (-0.32mm, P

Objective Methylene blue (MB) is frequently administered during fiberoptic endoscopic evaluation of swallowing (FEES) to enhance visualization of pharyngeal bolus transit. However, the safety of MB is being questioned since serious adverse events (AEs) such as hemodynamic instability, hemolysis, and serotonin syndrome were reported. The aim of this study is a systematic analysis of the literature to obtain an evidence-based overview of AEs due to oral administration of MB and to determine its safety as a food dye during swallowing assessment. Methods A systematic literature search was carried out in PubMed, Embase, and Cochrane Library. Two reviewers independently selected articles describing oral administration of MB as a main diagnostic/therapeutic intervention, dosage, and AEs. Expert opinions, conference papers, sample size < 10, and animal studies were excluded. Level of evidence of the included studies was determined. Results A total of 2264 unduplicated articles were obtained. Seventeen studies met the inclusion criteria with 100% agreement between the two reviewers. Among these, twelve studies were randomized controlled trials. In a pooled population of 1902 patients receiving oral MB, three serious AEs were reported related to MB. Non-serious AEs showed a dose-related trend and were usually mild and self-limiting. A meta-analysis could not be performed as studies were methodologically too heterogeneous. Conclusion Serious AEs due to oral administration of MB are rare (n = 3, 0.16%). MB-related non-serious AEs are mild, self-limiting, and show a dose-related trend. These findings indicate that it is safe to use small amounts of MB as a food dye during swallowing examinations.

BackgroundGiven the high prevalence of Cluster-C Personality Disorders (PDs) in clinical populations, disease burden, high societal costs and poor prognosis of comorbid disorders, a major gain in health care can be achieved if Cluster-C PDs are adequately treated. The only controlled cost-effectiveness study published so far found Individual Schema Therapy (IST) to be superior to Treatment as Usual (TAU). Group ST (GST) might improve cost-effectiveness as larger numbers can be treated in (>50%) less time compared to IST. However, to date there is no RCT supporting its (cost-) effectiveness. The overall aim of this study is to assess the evidence for GST for Cluster-C PDs and to improve treatment allocation for individual patients. Three main questions are addressed: 1) Is GST for Cluster-C PDs (cost-) effective compared to TAU? 2) Is GST for Cluster-C PDs (cost-) effective compared to IST? 3) Which patient-characteristics predict better response to GST, IST, or TAU?MethodsIn a multicenter RCT, the treatment conditions GST, IST, and TAU are compared in 378 Cluster-C PD patients within 10 sites. GST and IST follow treatment protocols and are completed within 1 year. TAU is the optimal alternative treatment available at the site according to regular procedures. Severity of the Cluster-C PD is the primary outcome, assessed with clinical interviews by independent raters blind for treatment. Functioning and wellbeing are important secondary outcomes. Assessments take place at week 0 (baseline), 17 (mid-GST), 34 (post-GST), 51 (postbooster sessions of GST), and 2 years (FU). Patient characteristics predicting better response to a specifc treatment are studied, e.g., childhood trauma, autistic features, and introversion. A tool supporting patients and clinicians in matching treatment to patient will be developed. An economic evaluation investigates the cost-effectiveness and costutility from a societal perspective. A process evaluation by qualitative methods explores experiences of participants, loved ones and therapists regarding recovery, quality of life, and improving treatment.Discussion This study will determine the (cost-)effectiveness of treatments for Cluster-C PDs regarding treatment type as well as optimal matching of patient to treatment and deliver insight into which aspects help Cluster-C-PD patients recover and create a fulfilling life. Trial registration Dutch Trial Register: NL9209. Registered on 28-01-2021

Introduction Cancer-related fatigue (CRF) is one of the most reported long-term effects breast cancer patients experience after diagnosis. Many interventions for CRF are effective, however, not for every individual. Therefore, intervention advice should be adjusted to patients' preferences and characteristics. Our aim was to develop an overview of eHealth interventions and their (preference sensitive) attributes. Methods eHealth interventions were identified using a scoping review approach. Eligible studies included breast cancer patients and assessed CRF as outcome. Interventions were categorized as physical activity, mind–body, psychological, ‘other’ or ‘combination’. Information was extracted on various (preference sensitive) attributes, like duration, intensity, peer support and costs. Results Thirty-five interventions were included and divided over the intervention categories. (Preference sensitive) attributes varied both within and between these categories. Duration varied from 4 weeks to 6 months, intensity from daily to own pace. Peer support was present in seven interventions and costs were known for six. Conclusion eHealth interventions exist in various categories, additionally, there is much variation in (preference sensitive) attributes. This provides opportunities to implement our overview for personalized treatment recommendations for breast cancer patients struggling with CRF. Taking into account patients' preferences and characteristics suits the complexity of CRF and heterogeneity of patients.

ObjectiveTo evaluate the efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with active ankylosing spondylitis (AS).MethodsThis phase III, multicenter, double-blind, placebo-controlled study (ClinicalTrials.gov: NCT01583374) randomized patients with active AS (1:1:1) to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily for 24 weeks, followed by a long-term extension phase (up to 5 yrs). The primary endpoint was Assessment of the Spondyloarthritis international Society 20 (ASAS20) response at Week 16. The effect of treatment on radiographic outcomes after 104 weeks was assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS).ResultsIn total, 490 patients with active AS were randomized in the study (placebo: n = 164; apremilast 20 mg twice daily: n = 163; apremilast 30 mg twice daily: n = 163). The primary endpoint of ASAS20 response at Week 16 was not met (placebo: 37%; apremilast 20 mg twice daily: 35%; apremilast 30 mg twice daily: 33%; P = 0.44 vs placebo). At Week 104, mean (SD) changes from baseline in mSASSS were 0.83 (3.6), 0.98 (2.2), and 0.57 (1.9) in patients initially randomized to placebo, apremilast 20 mg twice daily, and apremilast 30 mg twice daily, respectively. The most frequently reported adverse events through Week 104 were diarrhea, nasopharyngitis, upper respiratory infection, and nausea.ConclusionNo clinical benefit was observed with apremilast treatment in patients with active AS. The safety and tolerability of apremilast were consistent with its known profile.

SGLT2 inhibitors and GLP-1 receptor agonists are used in patients with type 2 diabetes as glucose lowering therapies, with additional benefits of weight loss and blood pressure reduction. Data from cardiovascular outcome trials have highlighted that these drugs confer protection against major cardiovascular disease in those with established atherosclerotic cardiovascular disease, reduce the risk of admission to hospital for heart failure, and reduce cardiovascular and all-cause mortality. Ongoing research using hard renal endpoints such as end stage kidney disease rather than surrogate markers might clarify the renoprotective benefits of both agents. When used for glucose lowering, SGLT2 inhibitors are most effective if the estimated glomerular filtration rate is more than 60 ml per min per 1.73m(2) at initiation and should be avoided where there is a risk of diabetic ketoacidosis. GLP- 1 receptor agonists are contraindicated in those with a history of medullary thyroid cancer and used with caution in patients with a history of pancreatitis of a known cause. These drugs are now second-line, or even arguably first-line, glucose lowering therapies in patients with cardiorenal disease, irrespective of glycaemic control. If an SGLT2 inhibitor or GLP-1 receptor agonist is considered suitable in patients with type 2 diabetes, treatment should be prioritised according to existing evidence: GLP-1 receptor agonists should be considered in patients at a high risk of, or with established, cardiovascular disease and SGLT2 inhibitors considered for patients with heart failure ( with reduced ejection fraction) or chronic kidney disease (with or without established cardiovascular disease). There is now compelling data on the benefits of these drugs for a range of other clinical indications even without type 2 diabetes, including for GLP-1 receptor agonists in patients with obesity and overweight with weight-related comorbidities.

Background The enormous health impact of the COVID-19 pandemic has refocused attention on measures to optimize immune function and vaccine response. Dietary deficiencies of micronutrients can weaken adaptive immunity. The aim of this review was to examine links between micronutrients, immune function and COVID-19 infection, with a focus on nutritional risks in subgroups of the Swiss population. Methods Scoping review on the associations between selected micronutrients (vitamins D and C, iron, selenium, zinc, and n-3 PUFAs) and immunity, with particular reference to the Swiss population. These nutrients were chosen because previous EFSA reviews have concluded they play a key role in immunity. Results The review discusses the available knowledge on links between sufficient nutrient status, optimal immune function, and prevention of respiratory tract infections. Because of the rapid spread of the COVID-19 pandemic, controlled intervention studies of micronutrients in the context of COVID-19 infection are now underway, but evidence is not yet available to draw conclusions. The anti-inflammatory properties of n-3 PUFAs are well established. In Switzerland, several subgroups of the population are at clear risk of nutrient deficiencies; e.g., older adults, multiple comorbidities, obesity, pregnancy, and institutionalized. Low intakes of n-3 PUFA are present in a large proportion of the population. Conclusion There are clear and strong relationships between micronutrient and n-3 PUFA status and immune function, and subgroups of the Swiss population are at risk for deficient intakes. Therefore, during the COVID-19 pandemic, as a complement to a healthy and balanced diet, it may be prudent to consider supplementation with a combination of moderate doses of Vitamins C and D, as well as of Se, Zn and n-3 PUFA, in risk groups., Clinical Nutrition ESPEN, 43, ISSN:2405-4577

Background: The enormous health impact of the COVID-19 pandemic has refocused attention on measures to optimize immune function and vaccine response. Dietary deficiencies of micronutrients can weaken adaptive immunity. The aim of this review was to examine links between micronutrients, immune function and COVID-19 infection, with a focus on nutritional risks in subgroups of the Swiss population.Methods: Scoping review on the associations between selected micronutrients (vitamins D and C, iron, selenium, zinc, and n-3 PUFAs) and immunity, with particular reference to the Swiss population. These nutrients were chosen because previous EFSA reviews have concluded they play a key role in immunity.Results: The review discusses the available knowledge on links between sufficient nutrient status, optimal immune function, and prevention of respiratory tract infections. Because of the rapid spread of the COVID-19 pandemic, controlled intervention studies of micronutrients in the context of COVID-19 infection are now underway, but evidence is not yet available to draw conclusions. The anti-inflammatory properties of n-3 PUFAs are well established. In Switzerland, several subgroups of the population are at clear risk of nutrient deficiencies; e.g., older adults, multiple comorbidities, obesity, pregnancy, and institutionalized. Low intakes of n-3 PUFA are present in a large proportion of the population.Conclusion: There are clear and strong relationships between micronutrient and n-3 PUFA status and immune function, and subgroups of the Swiss population are at risk for deficient intakes. Therefore, during the COVID-19 pandemic, as a complement to a healthy and balanced diet, it may be prudent to consider supplementation with a combination of moderate doses of Vitamins C and D, as well as of Se, Zn and n-3 PUFA, in risk groups. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism.

Psychologically based interventions aim to improve pain-related functioning by targeting pain-related fears, cognitions and behaviors. Mediation and moderation analyses permit further examination of the effect of treatment on an outcome. This systematic review and meta-analysis aims to synthetize the evidence of specific mediators and moderators (i.e., treatment targets) of psychologically based treatment effects on pain and disability. A total of 28 mediation and 11 moderation analyses were included. Thirteen mediation studies were included in a meta-analysis, and the rest was narratively synthetized. Reductions in pain-related fear (indirect effect [IE]: -0.07; 95% confidence interval [CI]: -0.11, -0.04) and catastrophizing (IE: -0.07; 95%CI: -0.14, -0.00), as well as increases in self-efficacy (IE: -0.07; 95%CI: -0.11, -0.04), mediated effects of cognitive behavioral therapy on disability but not on pain intensity, when compared to control treatments. Enhancing pain acceptance (IE: -0.17; 95%CI: -0.31, -0.03) and psychological flexibility (IE: -0.30; 95%CI: -0.41, -0.18) mediated acceptance and commitment therapy effects on disability. The narrative synthesis showed conflicting evidence, which did not support a robust moderated effect for any of the examined constructs. Overall, the methodological quality regarding mediation was low, and some key pitfalls are highlighted alongside recommendations to provide a platform for future research.

Psychologically based interventions aim to improve pain-related functioning by targeting pain-related fears, cognitions and behaviors. Mediation and moderation analyses permit further examination of the effect of treatment on an outcome. This systematic review and meta-analysis aims to synthetize the evidence of specific mediators and moderators (i.e., treatment targets) of psychologically based treatment effects on pain and disability. A total of 28 mediation and 11 moderation analyses were included. Thirteen mediation studies were included in a meta-analysis, and the rest was narratively synthetized. Reductions in pain-related fear (indirect effect [IE]: -0.07; 95% confidence interval [CI]: -0.11, -0.04) and catastrophizing (IE: -0.07; 95%CI: -0.14, -0.00), as well as increases in self-efficacy (IE: -0.07; 95%CI: -0.11, -0.04), mediated effects of cognitive behavioral therapy on disability but not on pain intensity, when compared to control treatments. Enhancing pain acceptance (IE: -0.17; 95%CI: -0.31, -0.03) and psychological flexibility (IE: -0.30; 95%CI: -0.41, -0.18) mediated acceptance and commitment therapy effects on disability. The narrative synthesis showed conflicting evidence, which did not support a robust moderated effect for any of the examined constructs. Overall, the methodological quality regarding mediation was low, and some key pitfalls are highlighted alongside recommendations to provide a platform for future research.

Although second-line antiandrogen therapy (SAT) is the standard of care in men with castration-resistant prostate cancer (CRPC), resistance inevitably occurs. One major proposed mechanism of resistance to SAT involves the emergence of androgen receptor (AR) splice variant-7, AR-V7. Recently, we developed MTX-23 using the principle of proteolysis targeting chimera (PROTAC) to target both AR-V7 and AR-full length (AR-FL). MTX-23 has been designed to simultaneously bind AR's DNA binding domain (DBD) and the Von Hippel–Lindau (VHL) E3 ubiquitin ligase. Immunoblots demonstrated that MTX-23's degradation concentration 50% (DC50) for AR-V7 and AR-FL was 0.37 and 2 μmol/L, respectively. Further studies revealed that MTX-23 inhibited prostate cancer cellular proliferation and increased apoptosis only in androgen-responsive prostate cancer cells. The antiproliferative effect of MTX-23 was partially reversed when either AR-V7 or AR-FL was overexpressed and was completely abrogated when both were overexpressed. To assess the potential therapeutic value of MTX-23, we next generated 12 human prostate cancer cell lines that are resistant to the four FDA-approved SAT agents—abiraterone, enzalutamide, apalutamide, and darolutamide. When resistant cells were treated with MTX-23, decreased cellular proliferation and reduced tumor growth were observed both in vitro and in mice. These results collectively suggest that MTX-23 is a novel PROTAC small molecule that may be effective against SAT-resistant CRPC by degrading both AR-V7 and AR-FL.

Purpose A scoping review was conducted with the objective to identify and map the available evidence from long-term studies on chronic non-specific low back pain (LBP), to examine how these studies are conducted, and to address potential knowledge gaps. Method We searched MEDLINE and EMBASE up to march 2021, not restricted by date or language. Experimental and observational study types were included. Inclusion criteria were: participants between 18 and 65 years old with non-specific sub-acute or chronic LBP, minimum average follow-up of > 2 years, and studies had to report at least one of the following outcome measures: disability, quality of life, work participation, or health care utilization. Methodological quality was assessed using the Effective Public Health Practice Project quality assessment. Data were extracted, tabulated, and reported thematically. Results Ninety studies met the inclusion criteria. Studies examined invasive treatments (72%), conservative (21%), or a comparison of both (7%). No natural cohorts were included. Methodological quality was weak (16% of studies), moderate (63%), or strong (21%) and generally improved after 2010. Disability (92%) and pain (86%) outcomes were most commonly reported, followed by work (25%), quality of life (15%), and health care utilization (4%). Most studies reported significant improvement at long-term follow-up (median 51 months, range 26 months–18 years). Only 10 (11%) studies took more than one measurement > 2 year after baseline. Conclusion Patients with persistent non-specific LBP seem to experience improvement in pain, disability and quality of life years after seeking treatment. However, it remains unclear what factors might have influenced these improvements, and whether they are treatment-related. Studies varied greatly in design, patient population, and methods of data collection. There is still little insight into the long-term natural course of LBP. Additionally, few studies perform repeated measurements during long-term follow-up or report on patient-centered outcomes other than pain or disability.

Introduction A substantial number of patients with PD experience relapse after the discontinuation of effective pharmacotherapy, leading to detrimental effects on the individuals and considerable societal costs. This suggests the need to optimize pharmacotherapy to minimize relapse risk. Area covered The present systematic review examines randomized, double-blind, placebo-controlled relapse prevention studies published over the last 20 years involving recommended medications. The authors aim to provide an overview of this topic and evaluate whether recent advances were achieved. Only seven studies were included, providing limited results. One-year maintenance pharmacotherapy with constant doses had protective effects against relapse in patients who had previously exhibited satisfactory responses to the same medication at the same doses. The duration of maintenance treatment did not influence relapse risk. No data were available concerning the use of lower doses or the predictors of relapse. Expert opinion Relapse prevention in PD has received limited attention. Recent progress and conclusive indications are lacking. Rethinking pharmacological research in PD may be productive. Collecting a wide range of clinical and individual features/biomarkers in large-scale, multicenter long-term naturalistic studies, and implementing recent technological innovations (e.g., electronic medical records/'big data' platforms, wearable devices, and machine learning techniques) may help identify reliable predictive models.

BACKGROUND: Acute pancreatitis (AP) is marked by a strong pro-inflammatory response, which may cause a systemic inflammatory response syndrome (SIRS), organ failure, and death. Early administration of omega-3 fatty acids (FA) may reduce the pro-inflammatory response and improve outcome in AP. A systematic review focusing on the safety and efficacy of omega-3 FA in AP is lacking.AIM: Evaluate the safety and efficacy of an intervention with omega-3 FA in acute pancreatitis and additionally in sepsis.METHODS: A systematic review and meta-analysis was performed using the PubMed, Embase, and Cochrane databases including only randomized controlled trials in AP and, for safety endpoints, in sepsis investigating intervention including omega-3 FA without other active components (e.g. addition of glutamine to the intervention). The primary outcome was mortality.RESULTS: After screening 1186 studies, five randomized trials (n = 229) with omega-3 FA in AP were included. In AP patients treated with omega-3 FA within 48 h after hospitalization, a non-significant reduction of mortality was seen (OR 0∙50, 95%CI 0∙13-1∙99, p = 0∙33), compared to controls. In two studies (n = 85), omega-3 FA reduced the risk of new onset of organ failure (OR 0∙33, 95%CI 0∙12-0∙93, p = 0∙04). Nine randomized trials with 312 patients suffering from sepsis (not pancreatitis related) demonstrated a reduced mortality (OR 0∙52, 95%CI 0∙28-0∙97, p = 0·04). None of these 14 randomized trials reported safety concerns.CONCLUSIONS: Administration of omega-3 FA could reduce the risk of new-organ failure in patients with AP. There were no safety issues reported of the early administration of omega-3 FA in any of the included studies. To show the real clinical benefit of omega-3 FA in AP, a large and pragmatic randomized controlled trial is needed.

Aim: To describe the development and implementation of a Dialogical Family Guidance (DFG) intervention, aimed at families with a child with neurodevelopmental disorders (NDD). Design: The DFG components are presented and the content of a DFG training course. Professionals' experiences after the DFG training were evaluated. Methods: Dialogical Family Guidance development phases and implementation process are examined. The Revised Standards for Quality Improvement Reporting Excellence checklist (SQUIRE 2.0) was used to provide a framework for reporting new knowledge. Results: The DFG training course seemed to increase possibilities of a more independent role as a nurse to deliver the DFG family intervention. The project showed that the use of dialogue can be difficult for some professionals. Analysis of the questionnaire completed after DFG training reported a high level of satisfaction. DFG training offered a new approach to deliver knowledge and understanding to families using dialogue, including tailored psychoeducation and emotional and practical guidance. publishedVersion

Heart failure (HF) remains a major global problem. In the Netherlands, 1.5-2.0% of the total population is diagnosed with HF. Over 30,000 HF patients are admitted annually in the Netherlands, and this number is expected to further increase given the ageing population and the chronic nature of HF. Despite ongoing efforts to reduce the burden of HF, morbidity and mortality rates of this disease remain high. However, several new treatment modalities have become available or are expected to become available in the coming years. This review will provide an overview of HF research conducted in the Netherlands (often in an international setting) that may have clinical consequences for diagnosis, treatment and prevention of HF, and will also evaluate outcomes of larger clinical trials that have been conducted in the Netherlands.

Heart failure (HF) remains a major global problem. In the Netherlands, 1.5–2.0% of the total population is diagnosed with HF. Over 30,000 HF patients are admitted annually in the Netherlands, and this number is expected to further increase given the ageing population and the chronic nature of HF. Despite ongoing efforts to reduce the burden of HF, morbidity and mortality rates of this disease remain high. However, several new treatment modalities have become available or are expected to become available in the coming years. This review will provide an overview of HF research conducted in the Netherlands (often in an international setting) that may have clinical consequences for diagnosis, treatment and prevention of HF, and will also evaluate outcomes of larger clinical trials that have been conducted in the Netherlands.

Early intervention in psychosis is crucial to improving patient response to treatment and the functional deficits that critically affect their long-term quality of life. Stratification tools are needed to personalize functional deficit prevention strategies at an early stage. In the present study, we applied topological tools to analyze symptoms of early psychosis patients, and detected a clear stratification of the cohort into three groups. One of the groups had a significantly better psychosocial outcome than the others after a 3-year clinical follow-up. This group was characterized by a metabolic profile indicative of an activated antioxidant response, while that of the groups with poorer outcome was indicative of oxidative stress. We replicated in a second cohort the finding that the three distinct clinical profiles at baseline were associated with distinct outcomes at follow-up, thus validating the predictive value of this new stratification. This approach could assist in personalizing treatment strategies.

Introduction A substantial number of patients with PD experience relapse after the discontinuation of effective pharmacotherapy, leading to detrimental effects on the individuals and considerable societal costs. This suggests the need to optimize pharmacotherapy to minimize relapse risk. Area covered The present systematic review examines randomized, double-blind, placebo-controlled relapse prevention studies published over the last 20 years involving recommended medications. The authors aim to provide an overview of this topic and evaluate whether recent advances were achieved. Only seven studies were included, providing limited results. One-year maintenance pharmacotherapy with constant doses had protective effects against relapse in patients who had previously exhibited satisfactory responses to the same medication at the same doses. The duration of maintenance treatment did not influence relapse risk. No data were available concerning the use of lower doses or the predictors of relapse. Expert opinion Relapse prevention in PD has received limited attention. Recent progress and conclusive indications are lacking. Rethinking pharmacological research in PD may be productive. Collecting a wide range of clinical and individual features/biomarkers in large-scale, multicenter long-term naturalistic studies, and implementing recent technological innovations (e.g., electronic medical records/'big data' platforms, wearable devices, and machine learning techniques) may help identify reliable predictive models.

BACKGROUNDStudies have shown that self-monitoring of blood pressure (BP) is effective when combined with co-interventions, but its efficacy varies in the presence of some co-morbidities. This study examined whether self- monitoring can reduce clinic BP in patients with hyper tension-related co-morbidity.METHODSA systematic review was conducted of articles published in Medline, Embase, and the Cochrane Library up to January 2018. Randomized controlled trials of self-monitoring of BP were selected and individual patient data (IPD) were requested. Contributing studies were prospectively categorized by whether they examined a low/ high-intensity co-intervention. Change in BP and likelihood of uncontrolled BP at 12 months were examined according to number and type of hypertension-related co-morbidity in a one-stage IPD meta-analysis.RESULTSA total of 22 trials were eligible, 16 of which were able to provide IPD for the primary outcome, including 6,522 (89%) participants with fol low-up data. Self-monitoring was associated with reduced clinic systollc BP compared to usual care at 12-month follow-up, regardless of the number of hypertension-related co-morbidities (-3.12 mm Hg, [95% confidence intervals -4.78, -1.46 mm Hg]; P value for interaction with number of morbidities = 0.260). Intense interventions were more effective than low-intensity interventions in patients with obesity (P CONCLUSIONSSelf-monitoring lower BP regardless of the number of hypertensic related co-morbidities, but may only be effective in conditions such obesity or stroke when combined with high-intensity co-interventions.

Although therapeutic hypothermia (TH) improves outcomes after neonatal encephalopathy (NE), the safety and efficacy of preemptive opioid sedation during cooling therapy is unclear. We performed a secondary analysis of the data from a large multicountry prospective observational study (Magnetic Resonance Biomarkers in Neonatal Encephalopathy [MARBLE]) to examine the association of preemptive morphine infusion during TH on brain injury and neurodevelopmental outcomes after NE. All recruited infants had 3.0 Tesla magnetic resonance imaging and spectroscopy at 1 week, and neurodevelopmental outcome assessments at 22 months. Of 223 babies recruited to the MARBLE study, the data on sedation were available from 169 babies with moderate (n = 150) or severe NE (n = 19). Although the baseline characteristics and admission status were similar, the babies who received morphine infusion (n = 141) were more hypotensive (49% vs. 25%, p = 0.02) and had a significantly longer hospital stay (12 days vs. 9 days, p = 0.009) than those who did not (n = 28). Basal ganglia/thalamic injury (score ≥1) and cortical injury (score ≥1) was seen in 34/141 (24%) and 37/141 (26%), respectively, of the morphine group and 4/28 (14%) and 3/28 (11%) of the nonmorphine group (p > 0.05). On regression modeling adjusted for potential confounders, preemptive morphine was not associated with mean (standard deviation [SD]) thalamic N-acetylaspartate (NAA) concentration (6.9 ± 0.9 vs. 6.5 ± 1.5; p = 0.97), and median (interquartile range) lactate/NAA peak area ratios (0.16 [0.12–0.21] vs. 0.13 [0.11–0.18]; p = 0.20) at 1 week, and mean (SD) Bayley-III composite motor (92 ± 23 vs. 94 ± 10; p = 0.98), language (89 ± 22 vs. 93 ± 8; p = 0.53), and cognitive scores (95 ± 21 vs. 99 ± 13; p = 0.56) at 22 months. Adverse neurodevelopmental outcome (adjusted for severity of encephalopathy) was seen in 26 (18%) of the morphine group, and none of the nonmorphine group (p = 0.11). Preemptive morphine sedation during TH does not offer any neuroprotective benefits and may be associated with increased hospital stay. Optimal sedation during induced hypothermia requires further evaluation in clinical trials.

INTRODUCTION: Intra-abdominal infections represent the second most frequently acquired infection in the intensive care unit (ICU), with mortality rates ranging from 20% to 50%. Candida spp. may be responsible for up to 10-30% of cases. This study assesses risk factors for development of intra-abdominal candidiasis (IAC) among patients admitted to ICU. METHODS: We performed a case-control study in 26 European ICUs during the period January 2015-December 2016. Patients at least 18 years old who developed an episode of microbiologically documented IAC during their stay in the ICU (at least 48 h after admission) served as the case cohort. The control group consisted of adult patients who did not develop episodes of IAC during ICU admission. Matching was performed at a ratio of 1:1 according to time at risk (i.e. controls had to have at least the same length of ICU stay as their matched cases prior to IAC onset), ICU ward and period of study. RESULTS: During the study period, 101 case patients with a diagnosis of IAC were included in the study. On univariate analysis, severe hepatic failure, prior receipt of antibiotics, prior receipt of parenteral nutrition, abdominal drain, prior bacterial infection, anastomotic leakage, recurrent gastrointestinal perforation, prior receipt of antifungal drugs and higher median number of abdominal surgical interventions were associated with IAC development. On multivariate analysis, recurrent gastrointestinal perforation (OR 13.90; 95% CI 2.65-72.82, p = 0.002), anastomotic leakage (OR 6.61; 95% CI 1.98-21.99, p = 0.002), abdominal drain (OR 6.58; 95% CI 1.73-25.06, p = 0.006), prior receipt of antifungal drugs (OR 4.26; 95% CI 1.04-17.46, p = 0.04) or antibiotics (OR 3.78; 95% CI 1.32-10.52, p = 0.01) were independently associated with IAC. CONCLUSIONS: Gastrointestinal perforation, anastomotic leakage, abdominal drain and prior receipt of antifungals or antibiotics may help to identify critically ill patients with higher probability of developing IAC. Prospective studies are needed to identify which patients will benefit from early antifungal treatment. ispartof: INFECTIOUS DISEASES AND THERAPY vol:11 issue:2 pages:827-840 ispartof: location:New Zealand status: published

IntroductionCancer-related fatigue (CRF) is one of the most reported long-term effects breast cancer patients experience after diagnosis. Many interventions forCRF are effective, however, not for every individual. Therefore, intervention advice should be adjusted to patients' preferences and characteristics. Our aim was to develop an overview of eHealth interventions and their (preference sensitive) attributes.MethodseHealth interventions were identified using a scoping review approach. Eligible studies included breast cancer patients and assessed CRF as outcome. Interventions were categorized as physical activity, mind–body, psychological, ‘other’ or ‘combination’. Information was extracted on various (preference sensitive) attributes, like duration, intensity, peer support and costs.ResultsThirty-five interventions were included and divided over the interventioncategories. (Preference sensitive) attributes varied both within and between thesecategories. Duration varied from 4 weeks to 6 months, intensity from daily to own pace. Peer support was present in seven interventions and costs were known for six.ConclusioneHealth interventions exist in various categories, additionally, there is much variation in (preference sensitive) attributes. This provides opportunities toimplement our overview for personalized treatment recommendations for breast cancer patients struggling with CRF. Taking into account patients' preferences and characteristics suits the complexity of CRF and heterogeneity of patients.

Cognitive control training has gained traction as an intervention for reducing anxiety and depression vulnerability in adults. There are, however, a limited number of studies investigating such training interventions for reducing symptomology of anxiety and depression in children and adolescents. Thus, we aimed to provide a robust review and qualitative synthesis of the available research in young people. Twelve articles met the inclusion criteria, and all were randomised control trials. Evidence of the efficacy of cognitive control training for relief of symptoms are reported separately for anxiety, depression, and other related psychological factors, and on the basis of type of cognitive control training paradigm. A lack of standardisation in relation to type of intervention, duration and context, outcome measures and population was observed. Results are discussed in terms of these variations and recommendations for future research are provided.

Backround: The aim of the current study is to investigate the efficacy and safety of Transcranial magnetic stimulation (TMS) treatment, a non-invasive brain stimulation technique, on depressive symptoms in treatment-resistant bipolar depression (TRBD). Subjects and methods: The study included 29 patients between the ages of 18-65, with bipolar disorder depressive episode according to DSM-5 and with the decision of non-response to treatment according to the Canadian Mood and Anxiety Treatment Network (CANMAT). Patients were divided into two groups double-blind-randomly, 20 sessions of TMS and 20 sessions of sham TMS were applied crossover. Hamilton Depression Rating Scale (HAM-D), Beck Depression Inventory (BDI), Young Mania Rating Scale (YMRS) and TMS Side Effect Questionnaire were applied to the patients before the treatment, at the 2nd week which is the crossover phase, and at the end of the treatment at 4th week. Results: In both groups, the severity of depression was decreased significantly according to HAM-D and BDI scores after the procedure. As well as active stimulation, some positive placebo effects were observed with sham stimulation. But the decreases seen in HAM-D and BDI scores and response to the treatment were higher during the weeks when the groups received active stimulation (respectively p=0.000, p=0.001, p=0.005). At the end of the study, according to HAM-D, 55.7\% of the patients showed response to the treatment, 24.13\% partial response. According to BDI, 41.37\% of the patients showed response to the treatment, and 31.03\% partial response. No associations were found between TMS response and sociodemographic - clinical features, or type of the disease (p>0.05). During the study, no serious adverse effects such as seizures or manic / hypomanic switches were observed. Conclusions: The results of our study showed that TMS treatment is an effective and safe treatment for patients with treatment-resistant bipolar depression.

OBJECTIVE: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies.DATA SOURCES: A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded.METHODS OF STUDY SELECTION: Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs.TABULATION, INTEGRATION, AND RESULTS: We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward.CONCLUSION: Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone.SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018090866.

INTRODUCTION: Apremilast is approved for the treatment of psoriasis and psoriatic arthritis (PsA). Real-world evidence on the efficacy and safety of apremilast in clinical practice is limited. We assessed the use of apremilast in patients with PsA in Belgium clinical practice. METHODS: The multicentre, observational, prospective APOLO study enrolled patients with active PsA initiating apremilast in Belgium between April 2017 and December 2018. Primary outcome was PsA Response Criteria (PsARC) after 6 months of apremilast treatment. Secondary outcomes included PsA Impact of Disease 12 (PsAID12) and Health Assessment Questionnaire Disability Index (HAQ-DI). Disease-specific outcomes and patient-reported outcomes (PROs) were analysed for patients who received apremilast within 30 days prior to their study inclusion and completed at least 150 days of treatment (reference set [REF]). RESULTS: Of 107 patients enrolled in the study, 106 received at least one dose of apremilast and 69 were included in the REF. PsARC response was achieved by 43.5% of patients (30/69) in the REF at month 6; mean global and composite scores including 68-joint count for pain/tenderness (68-TJC) and 66-joint count for swelling (66-SJC) improved, and 27% and 42% of patients with 68-TJC and 66-SJC > 0 at baseline had complete joint count resolution, respectively. Mean global and composite PsAID12 and HAQ-DI scores decreased at 6 months, indicating improved quality of life. Apremilast was well tolerated and the reported adverse events were in line with the known safety profile. CONCLUSION: Results from the APOLO study indicate that treatment with apremilast in Belgian clinical practice improves the signs and symptoms of PsA as well as patient quality of life. CLINICALTRIALS. GOV IDENTIFIER: NCT03096990. ispartof: ADVANCES IN THERAPY vol:39 issue:2 pages:1055-1067 ispartof: location:United States status: published

Frontiers in physiology 12, 771944 (2022). doi:10.3389/fphys.2021.771944, Published by Frontiers Research Foundation, Lausanne

Funding Information: The authors would like to thank the eight patients suffering from chronic venous disease in the United Kingdom National Health Service and the three lay members of the public without chronic venous disease, who evaluated the lay summaries of this guideline. The authors would also like to thank Fleur van Midwoud for graphical assistance (Figs. 3 and 4). Made available in DSpace on 2022-02-09T23:19:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2022 proof epub_ahead_of_print

OBJECTIVE: Different approaches in neuromodulation have been used to treat chronic low back pain in failed back surgery syndrome (FBSS) patients. We previously randomized 52 FBSS patients to be treated with spinal cord stimulation (SCS) and additional peripheral nerve field stimulation (PNFS) or SCS alone. At three months, we found a significant reduction of back pain in the PNFS-SCS group compared to the SCS group. In the subsequent open phase part of the study, all patients received optimal SCS and PNFS simultaneously. Here, we present the 12-month follow-up data on back and leg pain.MATERIALS AND METHODS: Data regarding back and leg pain, function, quality of life, patient satisfaction, anxiety and depression, and use of medication were collected by analyzing patients' questionnaires at 12 months and compared with data collected at baseline. Data were analyzed using multilevel regression models.RESULTS: A combined group of 50 subjects completed the 12-month follow-up. Back pain, measured on a 100-mm visual analog scale (VAS), significantly decreased over this period by 30.0 mm (95% CI: [-37.7/-22.4]; p CONCLUSIONS: At 12-month follow-up, PNFS in addition to SCS continues to provide a statistically significant and clinically relevant relief of low back pain in FBSS patients in whom SCS alone is effective for relief of leg pain only.

The aim of this study was to explore the themes that emerge when individuals are asked to describe their body functionality, and those that emerge when individuals are asked to describe their physical appearance. Data were gathered from undergraduate women and men’s (N = 75, Mage = 20.66) responses to a writing exercise (Alleva et al., 2014), wherein they were either asked to describe their body functionality or their physical appearance. Through thematic analysis, six themes were identified from participants’ descriptions of their body functionality (ordered by frequency): (a) evaluating the functionality of the body, (b) positive body-self connection, (c) resilient body, (d) comparisons to the norm, (e) body behind the scenes, and (f) enjoyment of body functions. Five themes were identified from participants’ descriptions of their physical appearance (ordered by frequency): (a) comparisons to the norm, (b) evaluating the appearance of the body – own evaluations, (c) evaluating the appearance of the body – other people’s evaluations, (d) the body project, and (e) appearance appreciation. Overall, the findings suggest that the themes that emerge when people are asked to reflect on their body functionality tend to be more positive, as they can be linked to positive embodiment, gratitude, and less self-objectification.

OBJECTIVE: Behavioral parent training (BPT) is an evidence-based intervention for children with attention-deficit/hyperactivity disorder (ADHD), but little is known about the effects of separate techniques parents learn in BPT. METHOD: In a three-armed randomized controlled microtrial including parents of 92 children (4-12 years) with ADHD, we examined the efficacy of two sessions parent training involving either stimulus control techniques (antecedent-based condition (AC)) or contingency management techniques (consequent-based condition (CC)), compared to a waitlist. Primary outcome was daily parent-rated problem behaviors, secondary outcomes were parent-rated symptoms of ADHD and oppositional defiant disorder (ODD), and mental health-care consumption. Measures were completed at baseline (T0), immediately after the training (T1), at two weeks (T2) and three months (T3) follow-up. We also explored whether child and parent characteristics moderated treatment effects. RESULTS: Compared to the waitlist, in the AC, daily rated problem behaviors improved at T1 (d= .56) and T2 (d= .65); in the CC, these behaviors only improved at T2 (d= .53). Daily rated problem behaviors within both conditions remained stable between T2 and T3. In the AC compared to the other conditions, inattention symptoms decreased at T1 and T2. For both active conditions compared to waitlist, hyperactivity-impulsivity symptoms decreased only at T2 and ODD symptoms did not decrease. No moderators were identified. Mental health-care consumption after training was low and did not differ between the active conditions. CONCLUSIONS: Brief training of parents in antecedent- or consequent-based techniques improves problem behaviors of children with ADHD. Antecedent-based techniques appear to be especially important to target inattention. ispartof: Journal Of Clinical Child And Adolescent Psychology vol:50 issue:6 pages:888-903 ispartof: location:England status: Published online

Key Points Question What is the evidence for nonpharmacological interventions to treat persistent postconcussion symptoms? Findings Following a systematic review and meta-analysis of 19 randomized clinical trials comprising 2007 participants, using the Grading of Recommendations, Assessment, Development, and Evaluations method, weak recommendations for the following were assigned: systematic provision of early information and advice, use of graded physical exercise, vestibular rehabilitation, manual treatment of neck and back, psychological treatment, and interdisciplinary rehabilitation. No studies were identified regarding oculomotor vision treatment, resulting in a consensus-based statement. Meaning Based on very low to low certainty of evidence or on consensus, individually tailored nonpharmacological treatment of persistent symptoms was recommended, both through specific disciplines and interdisciplinary rehabilitation., This systematic review and meta-analysis assesses the outcomes related to 7 nonpharmacological interventions for persistent postconcussion symptoms in adults and provides recommendations for clinical practice., Importance Persistent (>4 weeks) postconcussion symptoms (PPCS) are challenging for both patients and clinicians. There is uncertainty about the effect of commonly applied nonpharmacological treatments for the management of PPCS. Objective To systematically assess and summarize evidence for outcomes related to 7 nonpharmacological interventions for PPCS in adults (aged >18 years) and provide recommendations for clinical practice. Data Sources Systematic literature searches were performed via Embase, MEDLINE, PsycINFO, CINAHL, PEDro, OTseeker, and Cochrane Reviews (via MEDLINE and Embase) from earliest possible publication year to March 3, 2020. The literature was searched for prior systematic reviews and primary studies. To be included, studies had to be intervention studies with a control group and focus on PPCS. Study Selection A multidisciplinary guideline panel selected interventions based on frequency of use and need for decision support among clinicians, including early information and advice, graded physical exercise, vestibular rehabilitation, manual treatment of neck and back, oculomotor vision treatment, psychological treatment, and interdisciplinary coordinated rehabilitative treatment. To be included, studies had to be intervention studies within the areas of the predefined clinical questions, include a control group, and focus on symptoms after concussion or mild traumatic brain injury. Data Extraction and Synthesis Extraction was performed independently by multiple observers. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data abstraction and data quality assessment. Included studies were assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the Cochrane Risk of Bias (randomized clinical trials) tool. Meta-analysis was performed for all interventions where possible. Random-effects models were used to calculate pooled estimates of effects. The level and certainty of evidence was rated and recommendations formulated according to the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. Main Outcomes and Measures All outcomes were planned before data collection began according to a specified protocol. The primary outcomes were the collective burden of PPCS and another outcome reflecting the focus of a particular intervention (eg, physical functioning after graded exercise intervention). Results Eleven systematic reviews were identified but did not contribute any primary studies; 19 randomized clinical trials comprising 2007 participants (1064 women [53.0%]) were separately identified and included. Evidence for the 7 interventions ranged from no evidence meeting the inclusion criteria to very low and low levels of evidence. Recommendations were weak for early information and advice, graded physical exercise, vestibular rehabilitation, manual treatment of the neck and back, psychological treatment, and interdisciplinary coordinated rehabilitative treatment. No relevant evidence was identified for oculomotor vision treatment, so the panel provided a good clinical practice recommendation based on consensus. Conclusions and Relevance Based on very low to low certainty of evidence or based on consensus, the guideline panel found weak scientific support for commonly applied nonpharmacological interventions to treat PPCS. Results align with recommendations in international guidelines. Intensified research into all types of intervention for PPCS is needed.