OvidSP Platform Research Articles

A Systematic Review of Delta-9-Tetrahydrocannabinol (∆9-THC) in Astrocytic Markers.

Astrocytic reactivity in substance use disorders (SUDs) has been extensively studied, yet the molecular effect of delta-9-tetrahydrocannabinol (∆9-THC, the main psychoactive compound in cannabis) on glial cells, especially astrocytes, remains poorly understood. Exploring ∆9-THC's impact on astrocytic markers can provide insight into its effects on brain functions such as homeostasis, synaptic transmission, and response to neuronal injury. This systematic review synthesizes findings from studies investigating ∆9-THC's impact on astrocytic markers. A systematic review was conducted using EMBASE, Medline, and PsychoInfo via the OvidSP platform. Studies reporting astrocytic markers following ∆9-THC exposure in animals and humans were included. Data were extracted from twelve eligible full-text articles, and the risk of bias was assessed using the Systematic Review Center for Laboratory Animal Experimentation. This research identified several astrocytic markers, including glial fibrillary acidic protein (GFAP), nestin, and glutamate-aspartate transporter (GLAST). Both GFAP and nestin expressions increased in adulthood following adolescence and adult ∆9-THC exposure. An increase in GLAST expression was also noted during early development after ∆9-THC exposure. This review indicates varying levels of astrocytic reactivity to ∆9-THC across different developmental stages, including adolescence and adulthood. ∆9-THC appears to impact maturation, particularly during early developmental stages, and exhibits sex-dependent effects.

The Use of Contact Tracing Technologies for Infection Prevention and Control Purposes in Nosocomial Settings: A Systematic Literature Review.

Pandemic management and preparedness are more needed than ever before and there is widespread governmental interest in learning from the COVID-19 pandemic in order to ensure the availability of evidence-based Infection Prevention and Control measures. Contact tracing is integral to Infection Prevention and Control, facilitating breaks in the chain of transmission in a targeted way, identifying individuals who have come into contact with an infected person, and providing them with instruction/advice relating to testing, medical advice and/or self-isolation. This study aims to improve our understanding of the use of contact tracing technologies in healthcare settings. This research seeks to contribute to the field of Infection Prevention and Control by investigating how these technologies can mitigate the spread of nosocomial infections. Ultimately, this study aims to improve the quality and safety of healthcare delivery. A systematic literature review was conducted, and journal articles investigating the use of contact tracing technologies in healthcare settings were retrieved from databases held on the OvidSP platform between March and September 2022, with no date for a lower limit. In total, 277 studies were retrieved and screened, and 14 studies were finally included in the systematic literature review. Most studies investigated proximity sensing technologies, reporting promising results. However, studies were limited by small sample sizes and confounding factors, revealing contact tracing technologies remain at a nascent stage. Investment in research and development of new testing technologies is necessary to strengthen national and international contact tracing capabilities. This review aims to contribute to those who intend to create robust surveillance systems and implement infectious disease reporting protocols.

Palliative care interventions for patients with head and neck cancer: protocol for a scoping review

IntroductionA head and neck cancer (HNC) diagnosis significantly impacts a patient’s quality of life (QOL). Palliative care potentially improves their QOL. We will conduct a scoping review to identify existing...

Focal Brachytherapy for Localized Prostate Cancer: Systematic Review and Meta-Analysis

Advances in image-guided brachytherapy have increased the interest in focal brachytherapy (F-BT) approaches to optimize disease control, while reducing the toxicities associated whole gland treatments for prostate cancer (PCa). In this study we performed a systematic review to report biochemical control (BC), and genitourinary (GU) and gastrointestinal (GI) toxicity rates in patients with localized prostate cancer treated with F-BT as a definitive or salvage modality. This project was registered in the PROSPERO database (ID CRD42022320921). A comprehensive literature search was conducted in Cochrane Central databases, Cochrane Database of Systematic Reviews, Embase Classic +Embase, and Medline ALL, all from the OvidSP platform and Web of Science from Clarivate, from each database's inception to July 2022. Search was restricted to English and included terms: focal brachytherapy/prostate cancer, partial brachytherapy/prostate cancer. In total, 14862 articles were identified. Manuscripts that not related to focal or partial prostate brachytherapy, review papers and studies not reporting BC were excluded. After eliminating duplicates, and studies deemed irrelevant by consensus among three independent reviewers, 44 articles remained for in-depth review and data extraction. Thirty studies that included BC outcomes were included for this analysis, comprising 1556 patients treated with F-BT for PCa. Of these, 1094 (70%) and 462 (30%) underwent F-BT as definitive monotherapy or salvage, respectively; while 585 (38%) and 971 (62%) received HDR or LDR, respectively. For F-BT as monotherapy, the most commonly prescribed dose for HDR was 19 Gy in 1 fraction (range 19-24 Gy), and for LDR, 145 Gy (90-160Gy). Whereas for salvage F-BT, most common dose schedule of HDR was 19Gy in 1 fraction (19-27GY) and LDR 145Gy (144-145Gy). BC random effects estimate for F-BT monotherapy at 1-, 2-, 3-, and 5-years were 100% (P = 1.0), 96% (P = 0.45), 91% (P = 0.45) and 87% (P< 0.01), respectively. Whereas BC random effects estimate for salvage at 1-, 2-, 3-, and 5-years were 91% (P = 0.86), 68% (0.17), and 57% (P = 0.20), respectively. GI and GU grade 3-4 crude toxicity rates for monotherapy and salvage ranged from 0-3.33% and 0-17%, respectively. Over the last decade, there has been increasing interest in F-BT approaches, both as monotherapy and in the salvage setting. BC and toxicity profiles of F-BT appear favorable, and future studies directly comparing with whole-gland treatments are warranted.

Bevacizumab Treatment for Low-Grade Serous Ovarian Cancer: A Systematic Review.

Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation. Low-grade serous ovarian cancer (LGSOC) is a rare histologic subtype that lacks disease-specific evidence-based treatment regimens. However, LGSOC is relatively chemo-resistant and has a poor response to traditional treatments. Alternative treatments, including biologic therapies such as bevacizumab, have shown some activity in LGSOC. Thus, the objective of this systematic review is to determine the effect and safety of bevacizumab in the treatment of LGSOC. Following PRISMA guidelines, Medline ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase all from the OvidSP platform, ClinicalTrials.gov, International Clinical Trials Registry Platform, International Standard Randomised Controlled Trial Number Registry were searched from inception to February 2022. Articles describing bevacizumab use in patients with LGSOC were included. Article screening, data extraction, and critical appraisal of included studies were completed by two independent reviewers. The effect of bevacizumab on the overall response rate, progression-free survival, overall survival, and adverse effects were summarized. The literature search identified 3064 articles, 6 of which were included in this study. A total of 153 patients were analyzed; the majority had stage IIIC cancer (56.2%). The overall median response rate reported in the studies was 47.5%. Overall, bevacizumab is a promising treatment for LGSOC, with response rates higher than traditional treatment modalities such as conventional chemotherapy, and is often overlooked as a treatment tool. A prospective clinical trial evaluating the use of bevacizumab in LGSOC is necessary to provide greater evidence and support these findings.

Understanding strategies to improve medication adherence among persons with type 2 diabetes: A scoping review.

The objectives of this scoping review were to: (1) identify the target audience and contexts in which strategies to improve type 2 diabetes mellitus (T2DM) medication adherence have been used, (2) provide an overview of behaviour change techniques (BCTs) used, (3) describe the determinants of behaviour targeted by strategies and (4) to identify current gaps in strategies. A systemic search for articles related to T2DM, medication adherence and strategies was conducted in EMBASE, Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily using the OvidSP platform on 11 March 2021. All publications involving strategies to overcome medication non-adherence among adults with T2DM were included. Strategies were categorized according to the BCT taxonomy and the determinants of behaviour targeted by each strategy were classified by using the Theoretical Domains Framework (TDF). The search identified 58 articles and 61 strategies. The BCT categories Antecedents and Natural consequences and BCTs Feedback on outcome(s) of behaviour, Adding objects to the environment and Information about health consequences were identified most frequently as components of strategies resulting in statistically significant improvement in medication adherence. Strategies targeting the TDF domains Reinforcement and Beliefs about Consequences most often resulted in statistically significant improvements in adherence measures. The findings from this review identify BCTs and targeted behaviours with demonstrated success. Further exploration of the myriad of BCTs and the corresponding determinants of behaviour which were not accessed may be warranted for the development of future strategies to improve medication adherence in type 2 diabetes.

Understanding patient and caregiver perspectives using a dyad approach for data collection: A systematic review of the literature

Treatments outside of a clinical setting may be managed independently by the pediatric patient, independently by a caregiver, or by the patient and caregiver together. Best practices for pediatric clinical outcome assessment (COA) recommend patient-reported outcome (PRO) and/or observer-reported outcome (ObsRO) measures to assess the patient experience of a condition or its treatment. However, a dyad approach where patients and caregivers can complete assessments together may be useful for assessing a shared treatment experience that may not be adequately captured by a PRO and/or an ObsRO. A systematic, targeted literature review of empirical literature was conducted to identify and describe published studies detailing dyad patient-caregiver outcome reporting approaches. The search was run in the MEDLINE®, Embase, and PsycINFO® databases using the OvidSP platform and was limited to English-language studies published within 10 years of the conducted search on 28 September 2021, and 13 articles were selected for full-text review based on pre-specified criteria. Advantages and disadvantages for use of a dyad data collection approach are discussed. Though not appropriate for all settings, dyad data collection may be useful for situations where the best practice approach to measurement does not capture all relevant perspectives, or the use of PRO and ObsRO also does not comprehensively capture all relevant concepts. In following, it may offer a pragmatic solution that can minimize the use of proxy assessment and limit missing data, particularly in research involving a shared patient and caregiver treatment experience. Experience Framework This article is associated with the Staff & Provider Engagement lens of The Beryl Institute Experience Framework (https://www.theberylinstitute.org/ExperienceFramework). Access other PXJ articles related to this lens. Access other resources related to this lens.

Palliative care interventions for people who use substances during communicable disease outbreaks: a scoping review

ObjectivesWhen resources are strained during communicable disease outbreaks, novel palliative care interventions may be required to optimally support people who use substances with life-limiting illnesses. Therefore, we asked the question,...

Do social relationships mediate or moderate social inequalities in health? A systematic review protocol

IntroductionExplanations for health inequalities include material, behavioural and psychosocial pathways. Social relationships are an important determinant of health, and research has consistently found that a lack of support networks may diminish favourable health outcomes. There is some evidence that social network structures, partly shaped by socioeconomic factors, contribute to health inequalities. This protocol will summarise the systematic review process.Methods and analysesThe Systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. An electronic database search of MEDLINE, Embase Classic + Embase and PsychINFO using the OvidSP platform will be undertaken. Databases will be searched from the earliest date of entry until 10 June 2022. Articles that have quantitatively assessed the role of social relationships in mediating or moderating health inequalities will be included and any health outcome (mental/physical) will be considered. The database search will be supplemented by reference list screening of all relevant full-text articles identified through the search. Two independent reviewers will be responsible for screening of articles, data extraction and assessment of bias. Observational studies will be risk assessed for bias using a modified version of the Newcastle-Ottawa Quality Assessment Scale, and intervention studies will be assessed using the revised Cochrane risk-of-bias tool. It is anticipated that the eligible studies will be highly variable; therefore, a meta-analysis will only be considered if the available data of the selected studies are similar. If the studies are too heterogeneous, a narrative synthesis of the extracted data will be presented.ConclusionThe results of the systematic review will examine the link between social relationships and health inequalities. The findings of the review will identify gaps in knowledge where further research is needed.Systematic review registrationPROSPERO CRD42020181706

How common is hyperkalaemia? A systematic review and meta-analysis of the prevalence and incidence of hyperkalaemia reported in observational studies.

ABSTRACTBackgroundThe prevalence and incidence of hyperkalaemia, a potassium abnormality that can potentially have life-threatening consequences, are unclear.MethodsThe objective was to provide the most comprehensive overview of the epidemiology of hyperkalaemia to date within the general population, across different continents, in different healthcare settings and within pre-specified subgroups. Embase and MEDLINE were searched from database inception to 2 February 2021 using the Ovid SP platform. Relevant congress proceedings from 2018 to 2020 were also reviewed for inclusion. There was no language constraint applied. Observational studies from any time period and language reporting prevalence or incidence of hyperkalaemia within both adult and paediatric populations. Four investigators independently screened abstracts and assessed study quality of those meeting the pre-determined inclusion/exclusion criteria. Data extraction was conducted by the lead author with oversight from the senior author and data were pooled using a random-effects model. The measures assessed were the prevalence and incidence of hyperkalaemia. Prevalence was reported as a percentage, whilst incidence was reported as the rate per 100 person years.ResultsIn total, 542 articles were included from an initial search of 14 112 articles. Across all adult studies, we report a prevalence of hyperkalaemia (by any definition/threshold) of 6.3% [95% confidence interval (CI): 5.8–6.8%], with an incidence of hyperkalaemia in the adult population of 2.8 (2.3–3.3) cases per 100 person years. Prevalence within the general population was 1.3% (1.0–1.8%), whilst incidence was 0.4 (0.2–0.8) cases per 100 person years. There was a variation by sex with a prevalence of 6.3% (4.9–8.0%) in males and 5.1% (4.0–6.6%) in females. Prevalence also varied according to the definition/threshold of hyperkalaemia used: >5 mmol/L—8.0% (7.2–8.9), ≥5.5 mmol/L—5.9% (3.5–10.0) and ≥6.0 mmol/L—1.0% (0.8–1.4); hyperkalaemia (by any definition/threshold) was highest amongst patients with end-stage kidney disease (21.5%; 18.3–25.3), kidney transplant patients (21.8%; 16.1–29.5) and patients with acute kidney injury (24.3%; 19.3–30.7).ConclusionsThis novel review provides a comprehensive and valuable resource on the prevalence and incidence of hyperkalaemia to better inform clinicians, healthcare providers and health policy makers on the burden of hyperkalaemia across different healthcare settings, patient populations and continents.

Risk of Recurrence after Stopping Anticoagulants in Women with Combined Oral Contraceptive-Associated Venous Thromboembolism: A Systematic Review and Meta-Analysis

BackgroundAlthough combined oral contraceptives (COC) are considered a transient risk factor for venous thromboembolism (VTE), the risk of recurrence after discontinuation of anticoagulation is unclear. Few studies have focused on the risk of recurrence in this group; studies report variable results and are limited by small sample size. The risk of recurrence appears to be low, but this could relate to the young age of affected women. Deciphering the absolute VTE recurrence risk after a COC-associated VTE is crucial in helping clinicians and patients decide if anticoagulation could be discontinued after the initial treatment period.ObjectivesThe objectives of this systematic review and meta-analysis are to estimate the incidence of recurrent VTE among women with COC-associated VTE, compared with women with unprovoked VTE.MethodsWe searched the following databases: Cochrane Central Register of Controlled Trial, Cochrane Database of Systematic Reviews, Embase Classic +Embase, and Medline ALL, all from the OvidSP platform, from the database's inception to July 2020. Additional studies were identified by screening citations from included studies.Prospective cohort studies, randomized controlled trials (RCTs), and meta-analyses of prospective cohort studies or RCTs were reviewed by two authors for study inclusion (Figure 1). Studies were included if women had objectively confirmed COC-associated VTE, received a minimum of three months of anticoagulation, discontinued COC prior to or at time of discontinuation of anticoagulation, time of follow-up began after anticoagulation was stopped, and recurrent VTE data was available. Studies were excluded if patients were systematically treated with an alternative pharmacologic agent intended to reduce the risk of recurrent VTE such as aspirin. Authors of identified papers were contacted for additional data on critical variables. If there were multiple publications from a cohort, the study with the longest follow up was included.Two authors extracted study data and assessed included studies for risk of bias using the Newcastle Ottawa Scale. Meta-analysis was done using a random effects Poisson regression model. Heterogeneity was assessed using the I-squared measure.ResultsOur systematic review included 19 studies with a total of 1,537 women (5,828 patient years of follow up) with an index COC-associated VTE, and 1,974 women (7,798 patient years of follow up) with an index unprovoked VTE. Authors contributed additional unpublished data in 16 of the 19 studies. Overall, studies were at low risk of bias, with a mean of 7 stars (out of a possible 9) in the Newcastle Ottawa Scale.Among the 19 studies, the incidence rate of VTE recurrence in women with COC-associated VTE was 1.22 per patient year (95% confidence interval (CI) 0.94 to 1.59, I 2 = 6.4%, 95% prediction interval (PI) 0.81 to 1.85) (Figure 2). The incidence rate of VTE recurrence in women with an index unprovoked VTE not associated with COC was 3.89 per patient year (95% CI 2.98 to 5.07, I 2 =74.2%, 95% PI 1.37 to 11.03).The unadjusted incidence rate ratio of recurrent VTE comparing women with COC-associated events to women with unprovoked events was 0.34 (95% CI 0.26 to 0.45, I 2 = 2.6%, 95% PI 0.26 to 0.46). Only three studies had age-adjusted comparisons, but each with a different effect measure so they could not be combined, with a relative risk ratio 0.4 (95% CI 0.2 to 0.8) (also adjusted for site of VTE and congenital thrombophilia) (Eischer 2014), a hazard ratio of 0.11 (95% CI 0.01 to 0.85) (Kearon 2019), and an incidence rate ratio of 1 (95% CI 0.3 to 3.2) (Le Moigne 2013).ConclusionsThe estimated risk of VTE recurrence after a COC-associated VTE is low, and is lower compared to women with unprovoked VTE, however this comparison may be confounded by age. With only a minority of studies providing age adjusted analyses, the true difference remains unknown. Our meta-analysis is strengthened by the substantial contribution of unpublished data from individual study authors. This can help to guide clinicians and patient shared decision-making on the duration of anticoagulation. [Display omitted] DisclosuresLe Gal: LEO Pharma: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Bayer: Honoraria; Aspen: Honoraria; Sanofi: Honoraria. Schulman: Boehringer-Ingelheim: Research Funding; Octapharma: Research Funding. Skeith: CSL Behring: Research Funding; Leo Pharma: Honoraria; Sanofi: Honoraria.

P-131: Use of the European Organisation for research and treatment of cancer quality of life Multiple Myeloma questionnaire (EORTC QLQ-MY20): a review of the literature 25 years after development

<h3>Background</h3> The EORTC QLQ-MY20 is a widely used myeloma-specific patient-reported outcome measure originally developed in 1999. It consists of 20 items covering Disease Symptoms (DS), Side Effects (SE), Future Perspectives (FP) and Body Image (BI). Novel treatments and multiple lines of therapy mean the treatment for myeloma patients and life expectancy has changed dramatically and there is a need to ensure the measurement of health-related quality of life remains current for these patients. The original validation study was almost exclusively in newly diagnosed patients reflecting the nature of clinical trials at the time. This review was conducted as part of an EORTC funded grant to update the QLQ-MY20, with the aim of summarising the published literature from the QLQ-MY20 to date including any further validation results for the QLQ-MY20. <h3>Methods</h3> Literature search was conducted using the Ovid SP platform (Medline, EMBASE and PsycINFO) from 1996 (first release of the questionnaire). Abstracts were included if they were reporting: a clinical study using the QLQ-MY20 or validation studies. Information about the study design was extracted alongside whether the population were newly diagnosed or relapsed, and the supplementary instruments used alongside the QLQ-MY20. For randomised control trials, information on the type of analysis and results were also extracted. For validation studies data on the instrument structure and data distribution, reliability, validity and ability to detect change/interpretation of change scores was extracted. <h3>Results</h3> 656 abstracts were screened to 74 included papers (65 clinical studies, of which 21 were interventional clinical trials, and 9 validation studies). Supplementary instruments used alongside QLQ-C30 and MY20 included BPI-SF (Brief pain inventory short form), EQ-5D-5L (generic preference-based measure), FACT-GOG-Ntx (neurotoxicity) and the EORTC QLQ-CIPN20 (chemotherapy induced peripheral neuropathy). In contrast with the original validation study, 34 out of 43 clinical studies included either exclusively relapsed patients (n=24) or a mix of newly diagnosed and relapsed (n=9). DS and SE were the most commonly reported results from the QLQ-MY20. Further validation studies supported the factor structure, reliability and validity, with the only potential issue being observed ceiling effects for the BI subscale. <h3>Conclusions</h3> The shift in HRQOL measurement to patients experiencing multiple lines of treatment and novel treatments, highlights the need for updating the conceptual model for the QLQ-MY20. Interviews are currently underway internationally with 90 patients and 20 healthcare professionals to identify the issues relevant to myeloma patients today. The current questionnaire has been shown to be psychometrically valid and can be supplemented in the interim using item banks or existing questionnaires to cover new side effects specific to novel treatments.

A systematic review for the role of systemic thrombolysis in intermediate-risk (submassive) pulmonary embolism

Background: Pulmonary emboli (PE) represents an extended spectrum of diseases. 10% of submassive PE progress to massive PE, and while overall mortality is around 5%, it can reach 30%,1 highlighting the potential severity of submassive PE. Treatment of low and high-risk PE is rather straightforward. However, treating intermediate risk PE is challenging due to the potential risks associated with aggressive therapy. We assessed the effect of adding thrombolytic therapy to standard treatment with heparin on short-term mortality, clinical deterioration, and bleeding in intermediate-risk PE cases. Intermediate-risk PE in this systematic review is objectively confirmed PE either by computer tomography (CT) or ventilation/perfusion (V/Q) scan in normotensive patients (systolic blood pressure ≥ 90 mmHg) with evidence of right ventricular strain by echocardiography or CT with or without evidence of myocardial injury by raised cardiac biomarkers.2 Methods: A literature search was conducted using PubMed, OvidSP Platform, Google Scholar, BestBETs, The Cochrane Library - Databases, American College of Chest Physicians (ACCP), American Heart Association (AHA), European Society of Cardiology (ESC), American College of Emergency Physicians (ACEP), and NICE guidelines from 1946 to the 21st March 2018. References of retrieved articles were reviewed for other possibly related citations. The randomized controlled trials (RCTs) were studied and appraised using the Cochrane risk-of-bias tool (Table 1). Results: From 66 potentially relevant studies, six RCTs were published between 2002 and 2017 and included in this systematic review (Table 2). A total of 1568 patients were enrolled: 747 received thrombolytic therapy with alteplase (two trials, 155 patients) or tenecteplase (four trials, 592 patients), and 821 were treated with heparin only. None of these RCTs proved that adding thrombolytic therapy to standard anticoagulant treatment statistically decreased early mortality. The five studies looking at clinical deterioration proved that thrombolysis was beneficial. Five out of six RCTs resulted in a non-significant difference in major bleeding prevalence. Only the PEITHO3 trial proved the opposite. The incidence of minor bleeding was significantly higher in the four studies in which it was measured (Table 3). Conclusions: Currently, there is inadequate evidence to support the use of systematic thrombolysis for patients with acute intermediate-risk PE. Although it may prevent clinical deterioration which necessitates escalation of treatment in the short term, it comes with increased risk of bleeding. Individual risk-benefit patient assessment and shared decision making may be wise until better evidence to proceed otherwise is demonstrated. Larger clinical trials concerning reduced thrombolytic doses and prolonged infusion rate is essential.

PMU135 PATIENT-REPORTED OUTCOME MEASURES IN PATIENTS WITH CHRONIC OCULAR SURFACE PAIN : A LITERATURE REVIEW

Chronic ocular surface pain (COSP) is a persistent eye pain at the ocular surface lasting for a period longer than 3 months that interferes with regular daily activities, and is severely impacting patients’ health related quality of life (HRQoL).The aim of this study was to review the suitability of existing patient-reported outcome measures (PROMs) for use in clinical trials, assessing potential new therapies of COSP. Literature searches were performed in Medline and Embase using Ovid SP platform until March 2019. Specific search terms were used to identify studies assessing QoL in patients experiencing ocular pain. The review was complemented by searching relevant trials using PRO endpoints in ocular pain on clinicaltrials.gov. The measurement characteristics of the identified tools were reviewed in line with FDA’s 2009 PRO Guidance. A total of 1,130 abstracts were identified for initial screening and 177 were selected for full text review. In total 16 tools were identified, and of these, only four (Ocular Pain Assessment Survey (OPAS), Eye Sensation Scale (ESS), Neuropathic Pain Symptom Inventory (NPSI)-Eye and Brief Ocular Discomfort Inventory (BODI) specifically measured ocular pain. OPAS and ESS were originally developed for measuring ocular pain, whereas NPSI-Eye and BODI are modified versions of generic pain scales. As OPAS assesses the most critical HRQoL impacts of COSP such as impact on visual functioning, mood, sleep in addition to severity and type of pain assessment, it appears being the most adequate tool for its usage in future clinical trials. Among the PROMs identified for usage in future COSP clinical trials, OPAS appears to be the most suitable one. Further investigation is needed to ensure that OPAS is an appropriate and well-validated tool to assess new treatments for COSP in accordance with regulatory requirements.

Antimicrobial efficacy of commercially available endodontic bioceramic root canal sealers: A systematic review.

BackgroundRecently, a new generation of bioceramic root canal sealers has been introduced onto the market. Many in vitro studies have investigated the antimicrobial properties of these sealers, but their comparative efficacy in antimicrobial activity is still unknown.MethodologyThree electronic databases were searched: MEDLINE and Embase via the OvidSP platform, and Web of Science, up to June 25, 2019. Studies were included irrespective of study design, type of publication and language. Reporting quality was assessed by two authors independently. Meta-analysis was not performed due to studies being highly heterogeneous.ResultsWe included 37 studies that analysed the antimicrobial effects of bioceramic sealers. Most of them used a planktonic cell model, with the exception of nine studies which used biofilms. It was not possible to make direct comparison of results from studies and to give a clear conclusion about the comparative antimicrobial activity of these materials because the studies used heterogeneous sources and ages of microorganisms, setting and contact times of sealers, and antimicrobial tests. Furthermore, some materials showed completely different results when tested with different methods.ConclusionsIn conclusion, multiple in vitro studies have shown that bioceramic sealers may have various degrees of antimicrobial activity. However, it is still impossible to make conclusions about their comparative efficacy and to recommend the use of one over another in clinical practice because the studies available were conducted in different ways, which makes meta-analysis futile. A uniform methodological approach, consistent definitions and studies on humans are urgently needed in this field of research so that recommendations for practice can be made.

Incidence of Brain Metastases in Nonmetastatic and Metastatic Breast Cancer: Is There a Role for Screening?

BackgroundCurrent National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines recommend against screening breast cancer patients for asymptomatic brain metastases. Because brain metastases are a major cause of morbidity and mortality from breast cancer, we undertook a literature review to ascertain whether there might be a role for brain metastases screening in high-risk patient subgroups. Materials and MethodsA literature search was conducted on the OvidSP platform in the MedLine database, using MeSH terms and subject headings related to breast cancer, brain metastases, and incidence. The search was conducted without language or publication restrictions, and included articles indexed from January 1, 2006 to June 10, 2018. Experimental and observational studies that reported the incidence of brain metastases in patients with nonmetastatic or metastatic breast cancer were included. ResultsOne hundred seventy studies were identified, with 33 included in the final analysis. Among nonmetastatic breast cancer patients, incidence of brain metastases as site of first recurrence per year of median follow-up ranged from 0.1% to 3.2%. Although incidence of brain metastases was much higher among the metastatic breast cancer population overall, it was particularly high among metastatic HER2-overexpressing (HER2+) and triple-negative populations, ranging between 22% and 36% for the former, and 15%-37% for the latter in the absence of screening. ConclusionIn patients with nonmetastatic breast cancer, screening for asymptomatic brain metastases cannot currently be justified. However, due to the high incidence of brain metastases among patients with metastatic HER2+ and triple-negative breast cancer, studies to determine the value of screening for brain metastases should be undertaken in these subgroups.

Prevalence of diabetic retinopathy in children and young people living with diabetes: protocol for a systematic review

IntroductionThe frequency of diabetes mellitus in childhood is increasing. Thus, more children and young people are at risk of developing diabetic retinopathy and diabetes related visual impairment. However, there is...

Risk Factors for Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review.

Although a number of risk factors have been associated with invasive fungal disease (IFD), a systematic review of the literature to document pediatric-specific factors has not been performed. We used the Ovid SP platform to search Medline, Medline In-Process, and Embase for studies that identified risk factors for IFD in children with cancer or those who undergo hematopoietic stem cell transplantation (HSCT). We included studies if they consisted of children or adolescents (<25 years) who were receiving treatment for cancer or undergoing HSCT and if the study evaluated risk factors among patients with and those without IFD. Among the 3566 studies screened, 22 studies were included. A number of pediatric factors commonly associated with an increased risk for IFD were confirmed, including prolonged neutropenia, high-dose steroid exposure, intensive-timing chemotherapy for acute myeloid leukemia, and acute and chronic graft-versus-host disease. Increasing age, a factor not commonly associated with IFD risk, was identified as a risk factor in multiple published cohorts. With this systematic review, we have confirmed IFD risk factors that are considered routinely in daily clinical practice. Increasing age should also be considered when assessing patient risk for IFD. Future efforts should focus on defining more precise thresholds for a particular risk factor (ie, age, neutropenia duration) and on development of prediction rules inclusive of individual factors to further refine the risk prediction.

Associations Between Hydration Status, Intravenous Fluid Administration, and Outcomes of Patients Infected With Shiga Toxin–Producing Escherichia coli

The associations between hydration status, intravenous fluid administration, and outcomes of patients infected with Shiga toxin-producing Escherichia coli (STEC) remain unclear. To determine the relationship between hydration status, the development and severity of hemolytic uremic syndrome (HUS), and adverse outcomes in STEC-infected individuals. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials via the OvidSP platform, PubMed via the National Library of Medicine, CINAHL Plus with full text, Scopus, Web of Science, ClinicalTrials.gov, reference lists, and gray literature were systematically searched. Two reviewers independently identified studies that included patients with hydration status documentation, proven or presumed STEC infection, and some form of HUS that developed. No language restrictions were applied. Two reviewers independently extracted individual study data, including study characteristics, population, and outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale; strength of evidence was adjudicated using the Grading of Recommendations Assessment, Development, and Evaluation method. Meta-analyses were conducted using random-effects models. Development of HUS, complications (ie, oligoanuric renal failure, involvement of the central nervous system, or death), and interventions (ie, renal replacement therapy). Eight studies comprising 1511 patients (all children) met eligibility criteria. Unpublished data were provided by the authors of 7 published reports. The median risk-of-bias score was 7.5 (range, 6-9). No studies evaluated the effect of hydration during STEC infections on the risk for HUS. A hematocrit value greater than 23% as a measure of hydration status at presentation with HUS was associated with the development of oligoanuric HUS (OR, 2.38 [95% CI, 1.30-4.35]; I2 = 2%), renal replacement therapy (OR, 1.90 [95% CI, 1.25-2.90]; I2 = 17%), and death (OR, 5.13 [95% CI, 1.50-17.57]; I2 = 55%). Compared with putatively hydrated patients, clinically dehydrated patients had an OR of death of 3.71 (95% CI, 1.25-11.03; I2 = 0%). Intravenous fluid administration up to the day of HUS diagnosis was associated with a decreased risk of renal replacement therapy (OR, 0.26 [95% CI, 0.11-0.60]). Two predictors of poor outcomes for STEC-infected children were identified: (1) the lack of intravenous fluid administration prior to establishment of HUS and (2) a higher hematocrit value at presentation. These findings point to an association between dehydration and adverse outcomes for children with HUS.

Incidence of skeletal morbidity rates over time in patients with multiple myeloma-related bone disease as reported in randomized trials employing bone-modifying agents

The purpose of this review was to investigate if advances in bone-targeted therapies have decreased the incidence of skeletal morbidity rates over time in patients with multiple myeloma-related bone disease. A literature search was conducted over the OvidSP platform in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials to identify Phase III results from bone-targeted therapy trials in patients with multiple myeloma. The skeletal morbidity rate was the end point of interest, and for each study, a mean year of enrollment ([start of enrollment + end of enrollment]/2) was calculated. A total of eight study arms were identified, with only two placebo arms; therefore, a weighted linear regression was not feasible and only intervention treatment arms were analyzed. A statistically significant downward trend in the skeletal morbidity rate was observed in all intervention arms. The incidence of skeletal morbidity rates has decreased significantly over time in patients with multiple myeloma.