Factors influencing in-hospital prescribing errors: A systematic review.

AIM: In-hospital prescribing errors (PEs) may result in patient harm, prolonged hospitalization and hospital (re)admission. These events are associated with pressure on healthcare services and significant healthcare costs. To develop targeted interventions to prevent or reduce in-hospital PEs, identification and understanding of facilitating and protective factors influencing in-hospital PEs in current daily practice is necessary, adopting a Safety-II perspective. The aim of this systematic review was to create an overview of all factors reported in the literature, both protective and facilitating, as influencing in-hospital PEs. METHODS: PubMed, EMBASE.com and the Cochrane Library (via Wiley) were searched, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement, for studies that identified factors influencing in-hospital PEs. Both qualitative and quantitative study designs were included. RESULTS: Overall, 19 articles (6 qualitative and 13 quantitative studies) were included and 40 unique factors influencing in-hospital PEs were identified. These factors were categorized into five domains according to the Eindhoven classification ('organization-related', 'prescriber-related', 'prescription-related', 'technology-related' and 'unclassified') and visualized in an Ishikawa (Fishbone) diagram. Most of the identified factors (87.5%; n = 40) facilitated in-hospital PEs. The most frequently identified facilitating factor (39.6%; n = 19) was 'insufficient (drug) knowledge, prescribing skills and/or experience of prescribers'. CONCLUSION: The findings of this review could be used to identify points of engagement for future intervention studies and help hospitals determine how to optimize prescribing. A multifaceted intervention, targeting multiple factors might help to circumvent the complex challenge of in-hospital PEs.

Methodological aspects of in vivo axial loading in rodents: a systematic review.

Axial loading in rodents provides a controlled setting for mechanical loading, because load and subsequent strain, frequency, number of cycles and rest insertion between cycles, are precisely defined. These methodological aspects as well as factors, such as ovariectomy, aging, and disuse may affect the outcome of the loading test, including bone mass, structure, and bone mineral density. This review aims to overview methodological aspects and modifying factors in axial loading on bone outcomes. A systematic literature search was performed in bibliographic databases until December 2021, which resulted in 2183 articles. A total of 144 articles were selected for this review: 23 rat studies, 74 mouse studies, and 47 knock out (KO) mouse studies. Results indicated that peak load, frequency, and number of loading cycles mainly affected the outcomes of bone mass, structure, and density in both rat and mouse studies. It is crucial to consider methodological parameters and modifying factors such as age, sex-steroid deficiency, and disuse in loading protocols for the prediction of loading-related bone outcomes.

Cardiovascular events in anti-neutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis of observational studies.

OBJECTIVES: Several chronic inflammatory diseases are associated with cardiovascular disease, but the risk in ANCA-associated vasculitis is poorly quantified. The aim of the present study was to review the evidence for an increased cardiovascular risk, including ischaemic heart disease, cerebrovascular accidents and peripheral arterial disease, in patients with ANCA-associated vasculitis. METHODS: A comprehensive systematic review was conducted in accordance with guidelines of preferred reporting items for systematic reviews and meta-analyses. The databases PubMed, Embase.com and the Cochrane Library (Wiley) were searched for original observational studies comparing vasculitis patients with at least one control group. Summary estimates were derived with a random-effects model and reported as relative risks. RESULTS: One thousand three hundred and seventy-five studies were identified. Seven studies were included, comprising almost 14 000 ANCA-associated vasculitis patients vs general population controls in six studies and chronic kidney disease patients in one study. ANCA-associated vasculitis carried a relative risk of 1.65 (95% CI: 1.23, 2.22) for all cardiovascular events, 1.60 (95% CI: 1.39, 1.84) for ischaemic heart disease and 1.20 (95% CI: 0.98, 1.48) for cerebrovascular accidents. We did not find studies that addressed the risk for peripheral arterial disease separately. No heterogeneity was seen in the estimates. CONCLUSION: This meta-analysis of observational studies supports an increase in cardiovascular risk in patients with ANCA-associated vasculitis of ∼65%, similar to that found in other chronic inflammatory diseases. Hence, there is a clear need for active cardiovascular risk management in patients with ANCA-associated vasculitis.

Measuring implementation fidelity of school-based obesity prevention programmes: a systematic review.

BACKGROUND: Until now, there is no clear overview of how fidelity is assessed in school-based obesity prevention programmes. In order to move the field of obesity prevention programmes forward, the current review aimed to 1) identify which fidelity components have been measured in school-based obesity prevention programmes; 2) identify how fidelity components have been measured; and 3) score the quality of these methods. METHODS: Studies published between January 2001-October 2017 were selected from searches in PubMed, EMBASE, PsycINFO, CINAHL, Cochrane Library and ERIC. We included studies examining the fidelity of obesity prevention programmes (nutrition and/or physical activity and/or sitting) at school (children aged 4-18 year) measuring at least one component of implementation fidelity. A data extraction was performed to identify which and how fidelity components were measured. Thereafter, a quality assessment was performed to score the quality of these methods. We scored each fidelity component on 7 quality criteria. Each fidelity component was rated high (> 75% positive), moderate (50-75%) or low (< 50%). RESULTS: Of the 26,294 retrieved articles, 73 articles reporting on 63 different studies were included in this review. In 17 studies a process evaluation was based on a theoretical framework. In total, 120 fidelity components were measured across studies: dose was measured most often (N = 50), followed by responsiveness (N = 36), adherence (N = 26) and quality of delivery (N = 8). There was substantial variability in how fidelity components were defined as well as how they were measured. Most common methods were observations, logbooks and questionnaires targeting teachers. The quality assessment scores ranged from 0 to 86%; most fidelity components scored low quality (n = 77). CONCLUSIONS: There is no consensus on the operationalisation of concepts and methods used for assessing fidelity in school-based obesity prevention programmes and the quality of methods used is weak. As a result, we call for more consensus on the concepts and clear reporting on the methods employed for measurements of fidelity to increase the quality of fidelity measurements. Moreover, researchers should focus on the relation between fidelity and programme outcomes and determine to what extent adaptations to programmes have been made, whilst still being effective.

Do final-year medical students have sufficient prescribing competencies? A systematic literature review.

AIMS: Prescribing errors are an important cause of patient safety incidents and are frequently caused by junior doctors. This might be because the prescribing competence of final-year medical students is poor as a result of inadequate clinical pharmacology and therapeutic (CPT) education. We reviewed the literature to investigate which prescribing competencies medical students should have acquired in order to prescribe safely and effectively, and whether these have been attained by the time they graduate. METHODS: PubMed, EMBASE and ERIC databases were searched from the earliest dates up to and including January 2017, using the terms 'prescribing', 'competence' and 'medical students' in combination. Articles describing or evaluating essential prescribing competencies of final-year medical students were included. RESULTS: Twenty-five articles describing, and 47 articles evaluating, the prescribing competencies of final-year students were included. Although there seems to be some agreement, we found no clear consensus among CPT teachers on which prescribing competencies medical students should have when they graduate. Studies showed that students had a general lack of preparedness, self-confidence, knowledge and skills, specifically regarding general and antimicrobial prescribing and pharmacovigilance. However, the results should be interpreted with caution, given the heterogeneity and methodological weaknesses of the included studies. CONCLUSIONS: There is considerable evidence that final-year students have insufficient competencies to prescribe safely and effectively, although there is a need for a greater consensus among CPT teachers on the required competencies. Changes in undergraduate CPT education are urgently required in order to improve the prescribing of future doctors.

Effect of physical interventions on physical performance and physical activity in older patients during hospitalization: a systematic review.

BACKGROUND: To counteract decline in physical performance and physical activity in older patients during hospitalization, multiple physical interventions were developed. However, it is unknown whether these are effective in this particular population. This systematic review aimed to identify the effect of physical interventions on physical performance and physical activity in older patients during hospitalization. METHODS: The systematic search included PubMed, EMBASE, Cinahl, the Trials database of The Cochrane Library and SPORTdiscus from inception to 22 November 2017. Studies were included if the mean age of the patient cohort was 65 years and older and the effect of physical interventions on physical performance or physical activity was evaluated during hospitalization. RESULTS: Fifteen randomized controlled trials met the inclusion criteria. Overall, the effect of physical interventions on physical performance was inconsistent. Patient tailored interventions, i.e. continuously adapted to the capabilities of the patient were not found to be superior over interventions that were not. Physical activity as outcome measure was not addressed. Reporting of intensity of the interventions and adherence were frequently lacking. CONCLUSIONS: Evidence for the effect of physical interventions on physical performance in older patients during hospitalization was found uncertain. Further research on the efficacy of the intervention is needed, comparing types of intervention with detailed reporting of frequency, intensity and duration.

Clinicopathological Parameters in Patient Selection for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Cancer Metastases: A Meta-analysis.

OBJECTIVE: To improve patient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) by evaluating various preoperatively assessable clinicopathological parameters as markers for survival after CRS and HIPEC. SUMMARY BACKGROUND DATA: Peritoneal metastases (PMs) originating from colorectal cancer are treated with CRS and HIPEC. Despite increasing survival, high morbidity and mortality warrant selection of patients with optimal benefit from this treatment. Many studies report a number of variables to be associated with survival after CRS and HIPEC, but no definitive analysis has been made to validate various markers. METHODS: In concordance with PRISMA guidelines, we performed a literature search encompassing 4110 articles to select 50 articles that reported the influence of 1 or more clinicopathological variables on overall survival after CRS and HIPEC. In absence of RCTs, 25 cohort studies could be used to perform a meta-analysis on 10 prognostic variables. RESULTS: We determined that concurrent liver metastasis, lymph node metastasis, Eastern Cooperative Oncology Group score, tumor differentiation, and signet ring cell histology are all negative prognostic variables on overall survival after CRS and HIPEC. Conversely, sex and location of primary could not be validated as prognostic markers. More research is required to make definitive conclusions about neoadjuvant chemotherapy, onset of PMs, and mucinous histology. CONCLUSIONS: Current clinical practice, which selects patients based on extraperitoneal metastasis, lymph node stage, performance status, and tumor histology, is validated by our pooled analysis. Our data merit further research into neoadjuvant chemotherapy in the setting of CRS and HIPEC for PMs.

Systematic review and metaanalysis on nonclassic cardiovascular biomarkers after hypertensive pregnancy disorders.

OBJECTIVE: The aim of this study was to investigate which nonclassic cardiovascular biomarkers are associated with persistent endothelial dysfunction after pregnancy in women with a history of hypertensive pregnancy disorders compared with women with uncomplicated pregnancies. STUDY DESIGN: This was a systematic review and metaanalysis of observational studies. A search was performed in PubMed, Embase, Cochrane, and Cinahl including articles from inception to Feb. 27, 2013. Included were cohort studies and case-control studies. Cases were women with a history of hypertension in pregnancy, control subjects were women with a history of uncomplicated pregnancies. Of the 3136 found, 21 studies on 16 nonclassic cardiovascular biomarkers are described in this review; 12 studies on 5 biomarkers were included in the metaanalysis. RESULTS: Women with a history of hypertensive pregnancy disorders had a higher homocysteine level compared with women with a history of uncomplicated pregnancies (5 studies; pooled mean difference, 0.77 ng/mL; 95% confidence interval, 0.27-1.26; P < .01). For the other nonclassic cardiovascular biomarkers including markers in areas of inflammation, thrombosis, and angiogenesis, we found no significant differences. CONCLUSION: This review and metaanalysis showed that women with a history of hypertensive pregnancy disorders have higher homocysteine levels compared with women with a history of uncomplicated pregnancies. These data suggest persistent endothelial alteration after pregnancies complicated by hypertensive disorders.

The SpinBus architecture for scaling spin qubits with electron shuttling.

Quantum processor architectures must enable scaling to large qubit numbers while providing two-dimensional qubit connectivity and exquisite operation fidelities. For microwave-controlled semiconductor spin qubits, dense arrays have made considerable progress, but are still limited in size by wiring fan-out and exhibit significant crosstalk between qubits. To overcome these limitations, we introduce the SpinBus architecture, which uses electron shuttling to connect qubits and features low operating frequencies and enhanced qubit coherence. Device simulations for all relevant operations in the Si/SiGe platform validate the feasibility with established semiconductor patterning technology and operation fidelities exceeding 99.9%. Control using room temperature instruments can plausibly support at least 144 qubits, but much larger numbers are conceivable with cryogenic control circuits. Building on the theoretical feasibility of high-fidelity spin-coherent electron shuttling as key enabling factor, the SpinBus architecture may be the basis for a spin-based quantum processor that meets the scalability requirements for practical quantum computing.

The role of time in involving patients with cancer in treatment decision making: A scoping review.

BACKGROUND: Time is often perceived as a barrier to shared decision making in cancer care. It remains unclear how time functions as a barrier and how it could be most effectively utilized. OBJECTIVE: This scoping review aimed to describe the role of time in patient involvement, and identify strategies to overcome time-related barriers. METHODS: Seven databases were searched for any publications on patient involvement in cancer treatment decisions, focusing on how time is used to involve patients, the association between time and patient involvement, and/or strategies to overcome time-related barriers. Reviewers worked independently and in duplicate to select publications and extract data. One coder thematically analyzed data, a second coder checked these analyses. RESULTS: The analysis of 26 eligible publications revealed four themes. Time was a resource 1) to process the diagnosis, 2) to obtain/process/consider information, 3) for patients and clinicians to spend together, and 4) for patient involvement in making decisions. DISCUSSION: Time is a resource throughout the treatment decision-making process, and generic strategies have been proposed to overcome time constraints. PRACTICE VALUE: Clinicians could co-create decision-making timelines with patients, spread decisions across several consultations, share written information with patients, and support healthcare redesigns that allocate the necessary time.

Comparison of modern and conventional imaging techniques in establishing multiple myeloma-related bone disease: a systematic review.

This systematic review of studies compared magnetic resonance imaging (MRI), (18) F-fluorodeoxyglucose positron emission tomography (FDG-PET), FDG-PET with computerized tomography (PET-CT) and CT with whole body X-Ray (WBXR) or (whole body) CT in order to provide evidence-based diagnostic guidelines in multiple myeloma bone disease. A comprehensive search of 3 bibliographic databases was performed; methodological quality was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria (score 1-14). Data from 32 directly comparative studies were extracted. The mean QUADAS score was 7·1 (3-11), with quality hampered mainly by a poor description of selection and execution criteria. All index tests had a higher detection rate when compared to WBXR, with up to 80% more lesions detected by the newer imaging techniques; MRI (1·12-1·82) CT (1·04-1·33), PET (1·00-1·58) and PET-CT (1·27-1·45). However, the modern imaging techniques detected fewer lesions in the skull and ribs. In a direct comparison CT and MRI performed equally with respect to detection rate and sensitivity. This systematic review supports the International Myeloma Working Group guidelines, which recommend that WBCT can replace WBXR. In our opinion, the equal performance of MRI also indicates that it is a valuable alternative. As lesions of the skull and ribs are underdiagnosed by modern imaging techniques we advise additional X-rays of these regions. The consequences of this approach are discussed.

Sports-Related Health Problems in Para-Sports: A Systematic Review With Quality Assessment.

CONTEXT: Participation in sports is associated with a risk of sports-related health problems. For athletes with an impairment, sports-related health problems further burden an already restricted lifestyle, underlining the importance of prevention strategies in para-sports. OBJECTIVE: To provide a comprehensive overview with quality assessment of the literature on sports-related health problems, their etiology, and available preventive measures in para-sports following the steps of the Sequence of Prevention. DATA SOURCES: A literature search (in PubMed, Embase, SPORTDiscus, CINAHL and the Cochrane Library) was performed up to December 8, 2021, in collaboration with a medical information specialist. STUDY SELECTION: The search yielded 3006 articles, of which 64 met all inclusion criteria. STUDY DESIGN: Systematic review with quality assessment. LEVEL OF EVIDENCE: Level 3. DATA EXTRACTION: Two independent researchers carried out the screening process and quality assessment. One researcher extracted data, and the Sequence of Prevention categorized evidence. RESULTS: A total of 64 studies were included, of which 61 reported on the magnitude and risk factors of sports-related health problems, while only 3 reported on the effectiveness of preventive measures. Of these, 30 studies were of high quality. Most studies (84%) included elite-level athletes. The reported injury incidence varied widely between sports (0-91 per 1000 athlete days) and impairment categories (1-50 per 1000 athlete days). The same applies to illness incidence with regard to different sports (3-49 per 1000 athlete days) and impairment categories (6-14 per 1000 athlete days). CONCLUSION: This review shows the current vast range of reported sport-related health problems in para-sports. There is limited evidence concerning the severity of these sports-related health problems and inconclusive evidence on the risk factors. Lastly, the evidence regarding the development and effectiveness of preventive measures for para-athletes is sparse.

Is poor sleep quality associated with poor neurocognitive outcome in cancer survivors? A systematic review.

PURPOSE: Cancer-related neurocognitive impairment and poor sleep are prevalent in cancer survivors and have a negative impact on their quality of life. This systematic review studies the association between sleep disturbance and neurocognitive functioning, as well as the potential positive effects of sleep interventions on neurocognitive functioning in cancer survivors. In addition, we aimed at determining the potential positive effects of sleep interventions on neurocognitive functioning in this population. METHODS: Following PRISMA guidelines for reporting systematic reviews and meta-analyses, a comprehensive PubMed, Embase, PsycINFO, and CINAHL search was performed. Inclusion criteria were adult cancer survivors, self-reported or objective measures of neurocognitive functioning and sleep quality, or reports on the association between sleep and neurocognitive functioning. RESULTS: Of the 4,547 records retrieved, 17 studies were retained for this review. Twelve studies were correlational, and five reported on interventions aimed at improving sleep quality. All studies that included self-reported neurocognitive functioning found that poorer sleep was associated with worse neurocognitive functioning. In four out of eight studies, poorer sleep was associated with objective neurocognitive impairment. Three out of five interventional studies showed neurocognitive functioning improved with improved sleep. CONCLUSIONS: While poor sleep in cancer survivors is associated with self-reported neurocognitive impairment, the association between poor sleep and objective neurocognitive impairment is less evident. IMPLICATIONS FOR CANCER SURVIVORS: It is important that care providers are aware of the association between sleep and neurocognitive functioning and that improving sleep quality can be a way to decrease neurocognitive impairment in cancer survivors.

Resilience-enhancing interventions for antepartum depressive symptoms: systematic review.

BACKGROUND: Antepartum depressive symptoms (ADS) are highly prevalent and may affect the mother and child. Cognitive-behavioural therapy and interpersonal therapy are effective psychological interventions for depression. However, low adherence and high attrition rates in studies of prevention and treatment of antepartum depression suggest that these approaches might not be entirely suitable for women with mild/moderate ADS. Considering the protective association between resilience and ADS, women with ADS might benefit more from interventions focusing on promotion of mental well-being and resilience. AIMS: We aimed to provide an overview of studies evaluating the effectiveness of antepartum resilience-enhancing interventions targeting the improvement of ante- and postpartum depressive symptoms. We also investigated whether these interventions improve resilience and resilience factors in the peripartum period. METHOD: We conducted a systematic review, using PRISMA guidelines. Studies were eligible for inclusion when they utilised a randomised controlled trial or quasi-experimental design, studied pregnant women with ADS, and implemented psychological interventions that (a) aimed to reduce maternal ADS and/or prevent peripartum major depression, and (b) addressed one or more psychological resilience factors. RESULTS: Five of the six included cognitive-behavioural therapy interventions and all four mindfulness-based interventions were effective in reducing peripartum depressive symptoms and/or the incidence of depression. However, the methodological quality of most of the included studies was low to moderate. Only three studies assessed change in resilience factors. CONCLUSIONS: Resilience-enhancing interventions might be beneficial for mental well-being of pregnant women with ADS, although more rigorously designed intervention studies are needed.

Root Cause Analysis Using the Prevention and Recovery Information System for Monitoring and Analysis Method in Healthcare Facilities: A Systematic Literature Review.

OBJECTIVES: Unintended events (UEs) are prevalent in healthcare facilities, and learning from them is key to improve patient safety. The Prevention and Recovery Information System for Monitoring and Analysis (PRISMA)-method is a root cause analysis method used in healthcare facilities. The aims of this systematic review are to map the use of the PRISMA-method in healthcare facilities worldwide, to assess the insights that the PRISMA-method offers, and to propose recommendations to increase its usability in healthcare facilities. METHODS: PubMed, EMBASE.com, CINAHL, and The Cochrane Library were systematically searched from inception to February 26, 2020. Studies were included if the PRISMA-method for analyzing UEs was applied in healthcare facilities. A quality appraisal was performed, and relevant data based on an appraisal checklist were extracted. RESULTS: The search provided 2773 references, of which 25 articles reporting 10,816 UEs met our inclusion criteria. The most frequently identified root causes were human-related, followed by organizational factors. Most studies took place in the Netherlands (n = 20), and the sample size ranged from 1 to 2028 UEs. The study setting and collected data used for PRISMA varied widely. The PRISMA-method performed by multiple persons resulted in more root causes per event. CONCLUSIONS: To better understand UEs in healthcare facilities and formulate optimal countermeasures, our recommendations to further improve the PRISMA-method mainly focus on combining information from patient files and reports with interviews, including multiple PRISMA-trained researchers in an analysis, and modify the Eindhoven Classification Model if needed.

Blood-brain barrier permeability following conventional photon radiotherapy - A systematic review and meta-analysis of clinical and preclinical studies.

Radiotherapy (RT) is a cornerstone treatment strategy for brain tumours. Besides cytotoxicity, RT can cause disruption of the blood-brain barrier (BBB), resulting in an increased permeability into the surrounding brain parenchyma. Although this effect is generally acknowledged, it remains unclear how and to what extent different radiation schemes affect BBB integrity. The aim of this systematic review and meta-analysis is to investigate the effect of photon RT regimens on BBB permeability, including its reversibility, in clinical and preclinical studies. We systematically reviewed relevant clinical and preclinical literature in PubMed, Embase, and Cochrane search engines. A total of 69 included studies (20 clinical, 49 preclinical) were qualitatively and quantitatively analysed by meta-analysis and evaluated on key determinants of RT-induced BBB permeability in different disease types and RT protocols. Qualitative data synthesis showed that 35% of the included clinical studies reported BBB disruption following RT, whereas 30% were inconclusive. Interestingly, no compelling differences were observed between studies with different calculated biological effective doses based on the fractionation schemes and cumulative doses; however, increased BBB disruption was noted during patient follow-up after treatment. Qualitative analysis of preclinical studies showed RT BBB disruption in 78% of the included studies, which was significantly confirmed by meta-analysis (p < 0.01). Of note, a high risk of bias, publication bias and a high heterogeneity across the studies was observed. This systematic review and meta-analysis sheds light on the impact of RT protocols on BBB integrity and opens the discussion for integrating this factor in the decision-making process of future RT, with better study of its occurrence and influence on concomitant or adjuvant therapies.

Therapeutic Use of Microbubbles and Ultrasound in Acute Peripheral Arterial Thrombosis: A Systematic Review.

Catheter-directed thrombolysis (CDT) for acute peripheral arterial occlusion is time consuming and carries a risk of major hemorrhage. Contrast-enhanced sonothrombolysis (CEST) might enhance outcomes compared with standard CDT. In the study described here, we systematically reviewed all in vivo studies on contrast-enhanced sonothrombolysis in a setting of arterial thrombosis. A systematic search of the PubMed, Embase, Cochrane Library and Web of Science databases was conducted. Two reviewers independently performed the study selection, quality assessment and data extraction. Primary outcomes were recanalization rate and thrombus weight. Secondary outcome was any possible adverse event. The 35 studies included in this review were conducted in four different (pre)clinical settings: ischemic stroke, myocardial infarction, (peripheral) arterial thrombosis and arteriovenous graft occlusion. Because of the high heterogeneity among the studies, it was not possible to conduct a meta-analysis. In almost all studies, recanalization rates were higher in the group that underwent a form of CEST. One study was terminated early because of a higher incidence of intracranial hemorrhage. Studies on CEST suggest that adding microbubbles and ultrasound to standard intra-arterial CDT is safe and might improve outcomes in acute peripheral arterial thrombosis. Further research is needed before CEST can be implemented in daily practice.

At What Age Could Screening for Familial Retinoblastoma Be Discontinued? A Systematic Review.

The aim of this systematic review is to assess the latest age at diagnosis for detection of familial retinoblastoma in order to evaluate at what age screening of at-risk children could be discontinued. Extended screening beyond this age would result in unnecessary patient burden and costs. However, discontinuing screening prematurely would have the adverse effect of missing tumors. We performed a literature search (PubMed, Embase, CINAHL and the Cochrane Library) up until February of 2021 and systematically included studies where patients had a family history of retinoblastoma, a known age at diagnosis, and who were ophthalmologically screened for retinoblastoma from birth. A total of 176 familial retinoblastoma patients from 17 studies were included in this review. Based on 48 months of age being the latest age of diagnosis, ophthalmological screening for familial retinoblastoma could safely be discontinued at age four years.

Pathophysiological mechanisms explaining poor clinical outcome of older cancer patients with low skeletal muscle mass.

Low skeletal muscle mass is highly prevalent in older cancer patients and affects 5% to 89% depending on the type and stage of cancer. Low skeletal muscle mass is associated with poor clinical outcomes such as post-operative complications, chemotherapy toxicity and mortality in older cancer patients. Little is known about the mediating pathophysiological mechanisms. In this review, we summarize proposed pathophysiological mechanisms underlying the association between low skeletal muscle mass and poor clinical outcomes in older cancer patients including a) systemic inflammation; b) insulin-dependent glucose handling; c) mitochondrial function; d) protein status and; e) pharmacokinetics of anticancer drugs. The mechanisms of altered myokine balance negatively affecting the innate and adaptive immune system, and altered pharmacokinetics of anticancer drugs leading to a relative overdosage of anticancer drugs are best-substantiated. The effects of glucose intolerance and circulating mitochondrial DNA as a consequence of low skeletal muscle mass are topics of interest for future research. Restoring myokine balance through physical exercise, exercise mimetics, neuro-muscular activation and adapting anticancer drug dosing on skeletal muscle mass could be targeted approaches to improve clinical outcomes in older cancer patients with low skeletal muscle mass.

Placebo effects in low back pain: A systematic review and meta-analysis of the literature.

BACKGROUND AND OBJECTIVE: The current treatments of primary musculoskeletal low back pain (LBP) have a low to moderate efficacy, which might be improved by looking at the contribution of placebo effects. However, the size of true placebo effects in LBP is unknown. Therefore, a systematic review and meta-analysis were executed of randomized controlled trials investigating placebo effects in LBP. DATABASES AND DATA TREATMENT: The study protocol was registered in the international prospective register of systematic reviews Prospero (CRD42019148745). A literature search (in PubMed, Embase, The Cochrane Library, CINAHL and PsycINFO) up to 2021 February 16th yielded 2,423 studies. Two independent reviewers assessed eligibility and risk of bias. RESULTS: Eighteen studies were eligible for the systematic review and 5 for the meta-analysis. Fourteen of the 18 studies were clinical treatment studies, and 4 were experimental studies specifically assessing placebo effects. The clinical treatment studies provided varying evidence for placebo effects in chronic LBP but insufficient evidence for acute and subacute LBP. Most experimental studies investigating chronic LBP revealed significant placebo effects. The meta-analysis of 5 treatment studies investigating chronic LBP depicted a significant moderate effect size of placebo for pain intensity (SMD = 0.57) and disability (SMD = 0.52). CONCLUSIONS: This review shows a significant contribution of placebo effects to chronic LBP symptom relief in clinical and experimental conditions. The meta-analysis revealed that placebo effects can influence chronic LBP intensity and disability. However, additional studies are required for more supporting evidence and evidence for placebo effects in acute or subacute LBP. SIGNIFICANCE: This systematic review and meta-analysis provides evidence of true placebo effects in low back pain (LBP). It shows a significant contribution of placebo effects to chronic LBP symptom relief. The results highlight the importance of patient- and context-related factors in fostering treatment effects in this patient group. New studies could provide insight into the potential value of actively making use of placebo effects in clinical practice.