The Role of Endothelin in the Pathophysiology of Migraine—a Systematic Review

Purpose of Review

Vasoactive peptides play a key role in the attack-initiating cascade of migraine. Recent studies have highlighted a potentially important role for endothelin-1, a potent vasoconstrictor peptide, in migraine pathophysiology. Here, we review the current data on endothelin’s involvement in migraine.

Recent Findings

We identified 23 articles. Nine studies reported on endothelin-1 plasma concentrations in patients with migraine, eight studies investigated relevant genetic associations, five studies investigated endothelin-1 and spreading depression in animals, and one randomized controlled clinical trial tested the efficacy of an endothelin antagonist in the acute treatment of migraine in patients both with and without aura. Elevated endothelin-1 plasma levels have been reported in the early phase of migraine attacks. Genetic abnormalities related to the endothelin type A receptor have been reported in migraineurs. Endothelin-1 potently induces spreading depression in animals, which may explain the connection between endothelial irritation and migraine aura.

Summary

Endothelin-1 could be a primary factor in the attack-triggering cascade of migraine attacks with and without aura. Additional studies in humans and animal models are needed to further elucidate the role of endothelin-1 in migraine.

     

Adaptive Radiotherapy for Bladder Cancer—A Systematic Review

IntroductionRadiotherapy has been offered as a multimodality treatment for bladder cancer patients. Due to the significant variation of bladder volume observed throughout the course of treatment, large margins in the range of 20–30 mm have been used, unnecessarily irradiating a large volume of normal tissue. With the capability of visualizing soft tissue in cone beam computed tomography, there is opportunity to modify or to adapt the plan based on the variation observed during the course of treatment for quality improvement.MethodsA literature search was conducted in May 2016, with the aim of examining the adaptive strategies that have been developed for bladder cancer and assessing the efficacy in improving treatment quality. Among the 18 identified publications, three adaptive strategies were reported: plan of the day, patient-specific planning target volume, and daily reoptimisation.ResultsOverall, any of the adaptive strategies achieved a significant improvement in reducing the irradiated volume compared with the nonadaptive approach, outweighing the additional resource required for its execution.ConclusionThe amount and the type of resource required vary from strategy to strategy, suggesting the need for the individual institution to assess feasibility based on the existing infrastructure to identify the most appropriate strategy for implementation.     

Opioids for the Management of Dyspnea in Cancer Patients: Evidence of the Last 15 Years—A Systematic Review

The objective of this study was to review the evidence on the use of opioids for treatment of the dyspnea in adult cancer patients. A systematic literature review was conducted in the databases MEDLINE, CINAHL (EBSCO), ScienceDirect, and Cochrane Library of trials testing the effect of opioids in relieving dyspnea in cancer patients. Fourteen trials met the criteria for inclusion in the review. Eight randomized trials and six nonrandomized trials. All randomized clinical trials analyzed present risks of bias. Morphine has been the most studied strong opioid showing efficacy in alleviating dyspnea when administered, either orally or subcutaneously, in cancer patients. The potential benefit of the strong opioids in the alleviation of dyspnea in cancer patients is modest and limited to some opioids. More studies are needed to sufficiently support the role of opioids in dyspnea at rest, at exertion, and for breakthrough dyspnea and to clarify the safety issues.     

Characterizing Cardiac Involvement in Chronic Kidney Disease Using CMR—a Systematic Review

Purpose of Review

The aim of the review was to identify and describe recent advances (over the last 3 years) in cardiac magnetic resonance (CMR) imaging in patients with chronic kidney disease (CKD). We conducted a literature review in line with current guidelines.

Recent Findings

The authors identified 22 studies. Patients with CKD had left ventricular global and regional dysfunction and adverse remodeling. Stress testing with CMR revealed a reduced stress-response in CKD patients. Native T1 relaxation times (as a surrogate markers of fibrosis) are elevated in CKD patients, proportional to disease duration. Patients with CKD have reduced strain magnitudes and reduced aortic distensibility.

Summary

CMR has diagnostic utility to identify and characterize cardiac involvement in this patient group. A number of papers have described novel findings over the last 3 years, suggesting that CMR has potential to become more widely used in studies in this patient group.

     

Early Use of Fibrinogen Replacement Therapy in Postpartum Hemorrhage—A Systematic Review

Fibrinogen levels drop early in postpartum hemorrhage (PPH), and low fibrinogen levels predict outcomes. There is increasing interest in replacing fibrinogen early in severe PPH and this systematic review’s aim was to assess if early fibrinogen replacement therapy improves outcomes in severe PPH.We searched the following databases from inception to June 2019: CDSR and CENTRAL (The Cochrane Library), MEDLINE, Embase, CINAHL, PubMed, Transfusion Evidence Library, LILACS, Web of Science Conference Proceedings Citation Index-Science, ClinicalTrials.gov and the WHO International Clinical Trials Registry Portal. We included randomized (RCT) and well-designed controlled observational studies where fibrinogen replacement therapy was given early (within 90 minutes of bleeding) compared with standard protocol in pregnant women > 24 weeks’ gestation who developed PPH, defined as estimated blood loss ≥500 mL up to 24 hours post-delivery. Two independent reviewers extracted and reviewed the data on the primary outcome of allogeneic blood transfusion at 24 hours after intervention and secondary outcomes including all-cause mortality, rate of thrombosis, and the need for surgical and non-surgical interventions.We identified 5 eligible studies: 2 completed (total of 299 women) RCTs comparing fibrinogen concentrate with placebo, and 3 ongoing RCTs. There was no completed study assessing cryoprecipitate transfusion. There was variation of: timings of intervention administration; severity of PPH; fibrinogen doses and use of tranexamic acid. There was insufficient evidence that early administration of fibrinogen in PPH reduces the need for allogeneic blood transfusion at 24 hours (risk ratio 0.83 (95% CI 0.54–1.26), P = 0.38) (2 trials, 299 participants) or improves other outcomes. Both studies were underpowered to answer our outcomes.There is a lack of evidence that early fibrinogen replacement therapy improves outcomes in PPH. Future studies are needed to address this, underpinned by data on the optimal fibrinogen dose, protocol-driven approaches versus targeted therapy, and cost-effectiveness of cryoprecipitate versus fibrinogen concentrate therapy in PPH.     

Levodropropizine in the Management of Cough Associated with Cancer or Nonmalignant Chronic Disease–A Systematic Review

ABSTRACT

Cough associated with cancer or nonmalignant chronic disease is common and distressing. Levodropropizine, a peripherally acting drug, has been used as an alternative antitussive to opioids. The authors aimed to determine the efficacy and safety of levodropropizine in relieving cough associated with cancer or nonmalignant chronic disease. The authors searched five databases and hand searched relevant journals to identify randomized and nonrandomized controlled trials assessing the antitussive effect of levodropropizine for cough associated with cancer, chronic obstructive pulmonary disease (COPD), interstitial lung disease, or chronic heart failure. Study quality was assessed using a modified version of the Centre for Reviews and Dissemination criteria. The search yielded 58 references. Six were checked in more detail, and four studies were included. Two were randomized controlled trials (RCTs) testing levodropropizine against dihydrocodeine and moguisteine, and two were nonrandomized placebo-controlled studies, all with important limitations and high risk of bias. Levodropropizine was significantly more effective than placebo in reducing cough frequency and severity, and equally effective as dihydrocodeine or moguisteine. It was generally well tolerated. The authors conclude that the evidence for the antitussive efficacy of levodropropizine in these patients is scarce, and is further limited by the methodological weaknesses of the primary studies. Further well-designed research is needed to support its use.     

Early Treatment Response Evaluation in Patients with Diffuse Large B-Cell Lymphoma—A Pilot Study Comparing Volumetric MRI and PET/CT

Purpose  

The purpose of this study is to evaluate the time course of early chemotherapy response in patients with aggressive non-Hodgkin's lymphoma (NHL) by magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT).     

Safety and Effectiveness of Palliative Drug Treatment in the Last Days of Life—A Systematic Literature Review

Context

Dying patients commonly experience potentially distressing symptoms. Palliative care guidelines recommend opioids, anticholinergics, antipsychotics, and benzodiazepines for symptom relief.

A Systematic Review of Service-Learning in Medical Education: 1998–2012

Phenomenon: In the United States, the Affordable Care Act has increased the need for community-centered pedagogy for medical education such as service-learning, wherein students connect academic curriculum and reflections to address a community need. Yet heterogeneity among service-learning programs suggests the need for a framework to understand variations among service-learning programs in medical education. Approach: A qualitative systematic review of literature on service-learning and medical education was conducted for the period between 1998 and 2012. A two-stage inclusion criteria process resulted in articles (n = 32) on service-learning and Doctor of Medicine or Doctor of Osteopathic Medicine being included for both coding and analysis. Focused and selective coding were employed to identify recurring themes and subthemes from the literature. Findings: The findings of the qualitative thematic analysis of service-learning variation in medical education identified a total of seven themes with subthemes. The themes identified from the analysis were (a) geographic location and setting, (b) program design, (c) funding, (d) participation, (e) program implementation, (f) assessment, and (g) student outcomes. Insights: This systematic review of literature confirmed the existence of program heterogeneity among service-learning program in medical education. However, the findings of this study provide key insights into the nature of service-learning in medical education building a framework for which to organize differences among service-learning programs. A list of recommendations for future areas of inquiry is provided to guide future research.     

Cancer Deaths in Dundee—a Comparative Study

There has been a widely-shared suggestion that Dundee was well below average in providing for patients to die at home. Figures for service provision for terminal cancer patients in various areas of Scotland are based on statistics provided by the Information and Statistics Division, Scotland (ISD). Some inconsistencies in the ISD data led to the subsequent reworking of data to a set formula. The data showed that differences in the percentage of people dying in non-domiciliary settings in mainland Health Board areas became virtually the same if NHS Hospitals and non-NHS institutional settings are considered together.     

What Turns on a Migraine? A Systematic Review of Migraine Precipitating Factors

Migraine attacks rarely occur spontaneously in the absence of any possible precipitating factors. A systematic literature review of 25 publications revealed a consistent set of stimuli that have been identified as factors associated with the onset of a migraine attack. The weighted average of the “Top 10” trigger factors was determined. Stress was cited as the overall most common migraine precipitating factor, which was identified as a trigger factor by 58 % of 7187 migraineurs. The incidence of migraine precipitating factors, across various populations globally, demonstrates the clinical consistency of migraine in the human population. Future efforts aimed at mitigating these precipitating factors have the potential to significantly improve migraine management. However, the current healthcare system is unlikely to be able to develop detailed personalized management plans. There is a need to develop a novel approach to the identification and management of multiple trigger factors in individual migraineurs.     

Opportunities for Palliative Care in Patients With Burn Injury—A Systematic Review

ContextPatients with significant burn injuries likely have palliative care needs.ObjectivesWe performed a systematic review of existing evidence concerning the palliative care needs of burn patients.MethodsThrough November 26, 2018, we systematically searched PubMed, CINAHL, Embase, Web of Science, and Scopus, using terms representing burn injuries and the eight domains of quality palliative care as outlined by the National Consensus Project for Quality Palliative Care. Eligible articles involved burn-injured patients treated with an intervention targeting at least one of the eight domains.ResultsOur searches yielded 7532 unique records, which led to 238 articles for full review and 88 studies that met inclusion criteria. Seventy-five studies addressed the domain physical aspects of care and merit a separate systematic review; 13 studies were included in our final review. Four of the seven domains—processes of care, psychologic symptoms, social aspects, and end of life—were addressed by studies but three domains—spiritual, cultural, or ethics—were unaddressed. Included studies highlight potential benefits from peridischarge self-care education programs, peer support, and group therapy in improving quality of life. In patients with severe injuries, end-of-life decision-making protocols were associated with increased utilization of comfort-focused treatments.ConclusionMost existing palliative care-related research in burn patients addresses interventions for physical symptoms with minimal literature concerning other domains. Opportunities exist for further research of palliative care in burn populations with emphasis on addressing interventions for all domains and better standardizing the language and outcomes for the palliative care interventions.     

The Effects of Folic Acid Supplementation on Pro-inflammatory Mediators: a Systematic Review and Dose–Response Meta‐Analysis of Randomized Controlled Trials

PurposeDespite extensive research, findings regarding the effects of folic acid supplementation on inflammatory mediators have been controversial and inconclusive. This study therefore aimed to summarize the findings of all available clinical trials regarding the effects of folic acid supplementation on inflammatory biomarkers in adults.MethodsA systematic search was conducted of PubMed/MEDLINE, Scopus, Web of Science, EMBASE, and Google Scholar until April 2020. All randomized controlled trials that examined the influence of folic acid supplementation on C-reactive protein, interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were included. Pooled effect sizes were calculated based on the random effects model, and dose–response analysis was modeled by using a fractional polynomial model.FindingsIn total, 18 randomized controlled trials involving 2286 participants were analyzed. Folic acid supplementation significantly reduced serum levels of C-reactive protein (mean difference [MD], –0.21 mg/L; 95% CI, –0.41 to –0.01; n = 16), TNF-α (MD, –14.88 pg/mL; 95% CI, –23.68 to –6.09; n = 10), and IL-6 (MD, –0.93 pg/mL; 95% CI, –1.72 to –0.14; n = 11). Subgroup analyses suggested a significant reduction at doses ≤5 mg/d and studies longer than 12 weeks in duration. A significant nonlinear association was also found between folic acid dosage (P_nonlinearity <0.001) and duration of administration (P_nonlinearity <0.001) with serum TNF-α levels.ImplicationsThis meta-analysis indicates the beneficial effects of folic acid supplementation on pro-inflammatory cytokines. Further studies with a longer duration of administration, higher doses, and larger sample sizes should be performed exclusively on patients with chronic inflammatory disorders to elucidate the favorable role of folate intake on inflammatory biomarkers. International Prospective Register of Systematic Reviews identifier: CRD42021249947.     

Can Physical Exercise Prevent Chemotherapy-Induced Peripheral Neuropathy in Patients With Cancer? A Systematic Review and Meta-analysis

ObjectiveThis systematic review analyzed the effects of physical exercise programs in patients with cancer undergoing chemotherapy on chemotherapy-induced peripheral neuropathy (CIPN) prevention.Data SourcesPubMed, Web of Science, Scopus, and Cochrane Library were searched for relevant studies published before December 2020. Additional references were identified by manual screening of the reference lists.Study SelectionBased on the Population, Intervention, Comparator, Outcomes, and Study Designs strategy, randomized controlled trials in which physical exercise was applied before or during chemotherapy to prevent or ameliorate CIPN were included.Data ExtractionTwo reviewers blinded and independent screened the articles, scored methodologic quality, and extracted data for analysis. The review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Sensitivity and precision analysis databases was included. Risk of bias assessment and meta-analysis were conducted using the Cochrane tools.Data SynthesisOf 229 potentially relevant studies, 8 randomized controlled trials were included and scored. They comprise a total of 618 patients with cancer. MEDLINE and Scopus databases recorded the highest sensitivity. None of the studies achieved a “low” overall risk of bias. Four studies were included in meta-analysis for quality of life, and a significance standardized mean difference was found between groups from baseline of 14.62; 95% CI, 6.03-3.20, with a large effect size g=0.83; 95% CI, 0.48-1.18) in favor of physical exercise program compared with usual care.ConclusionsPhysical exercise at the onset of chemotherapy has shown promising effects on the prevention of CIPN, specially improving quality of life.     

Health Care Professionals’ Knowledge and Attitudes Toward Physical Activity in Cancer Patients: A Systematic Review

ObjectivesThe purpose of this study was to, combine current available literature across health professionals to determine commonalities and differences between knowledge and attitudes of physical activity (PA) and its importance within the cancer population. It aimed to identify any gaps in the literature to inform future study directions to enhance PA participation and improve health outcomes and quality of life.Data SourcesDesign: systematic review. Data sources: Google Scholar, EBSCO, PubMed, Scopus, Web of Science. Inclusion criteria: survey-based studies specifically reporting PA levels for both cancer patients and survivors from the perspective of oncology health care professionals. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was used to guide this review. The initial search highlighted 15,342 articles and returned 190 articles with relevant titles, of which 20 met the eligibility criteria; 15.8% of cancer patients reported to meeting PA guidelines during treatment and 36.5% after treatment. On average 58.1% of health care professionals self-reported discussing PA with their cancer patients, with the average referral rate to an exercise specialist or rehabilitation program being 18.3%.ConclusionOnly a limited number of health care professionals are initiating a discussion about PA with their cancer patients. Some health care professionals reported limited knowledge of PA guidelines for cancer patients. Their own personal PA levels do not seem to be associated with whether they discuss PA with their patients. Common barriers to providing PA advice were experienced across all health care professions such as time, limited referral pathways, and patient interest. Future research should be carried out to substantiate these barriers and discover which strategies could be implemented to improve the levels of PA discussions and referrals within clinical practice.Implications for Nursing PracticeGiven the position nurses hold within the health care system, it would be beneficial to upskill and improve their understanding of PA and exercise as medicine for the cancer population. This has enormous potential that could enhance PA advice and boost referrals to exercise professionals improving the health and quality of life of the cancer population.     

How Reliable Are Therapeutic Competence Ratings? Results of a Systematic Review and Meta-Analysis

Cognitive Therapy and Research - Assessments of psychotherapeutic competencies play a crucial role in research and training. However, research on the reliability and validity of such assessments is...     

Effectiveness of Surgical and Postsurgical Interventions for Carpal Tunnel Syndrome—A Systematic Review

Objective

To present an evidence-based overview of the effectiveness of surgical and postsurgical interventions for carpal tunnel syndrome (CTS).

Systematic Review of Factors Influencing Non–Medically Indicated Formula Supplementation of Newborns in the Hospital Setting

ObjectiveTo examine maternal and newborn factors that influence non–medically indicated (NMI) formula supplementation of newborns in the hospital setting.Data SourcesElectronic databases CINAHL and Ovid MEDLINE were searched for peer-reviewed articles published in English between January 1, 2000, and September 30, 2017.Study SelectionA total of 616 studies were returned from the search. After removal of duplicates, 558 studies remained, 531 of which were excluded based on factors of not being related to term newborns, not being published in a peer-reviewed journal, or study not completed in a hospital setting. Five studies were included that met the inclusion and exclusion criteria.Data ExtractionData from the five studies were extracted and compiled into a summary table.Data SynthesisSynthesis indicated that maternal ethnicity, educational level, and income influence the decision to provide NMI formula supplementation to newborns. First-time mothers and those with cesarean birth, no previous breastfeeding experience, female newborns, and large-for-gestational-age newborns were at greater risk for NMI formula supplementation. Neonates born at night are more likely to receive NMI formula supplementation, and NMI formula supplementation increases during the night hours and during the first 24 hours after birth.ConclusionIdentification of newborn/maternal risk factors, continuous breastfeeding support, and provision of consistent breastfeeding education to women are factors that influence NMI formula supplementation of newborns. With collaboration among hospital physicians, midwives, nurse practitioners, nurses, and lactation consultants to identify at-risk newborns, the goal of decreasing NMI formula supplementation of newborns in the hospital can be achieved.