Conflict of interest in clinical practice guideline development: a systematic review

Background

There is an emerging literature on the existence and effect of industry relationships on physician and researcher behavior. Much less is known, however, about the effects of these relationships and other conflicts of interest (COI) on clinical practice guideline (CPG) development and recommendations. We performed a systematic review of the prevalence of COI and its effect on CPG recommendations.

Methodology/Principal Findings

We searched Medline (1980 to March, 2011) for studies that examined the effect of COI on CPG development and/or recommendations. Data synthesis was qualitative. Twelve studies fulfilled inclusion criteria; 9 were conducted in the US. All studies reported on financial relationships of CPG authors with the pharmaceutical industry; 1 study also examined relationships with diagnostic testing and insurance companies. The majority of guidelines had authors with industry affiliations, including consultancies (authors with relationship, range 6–80%); research support (4–78%); equity/stock ownership (2–17%); or any COI (56–87%). Four studies reported multiple types of financial interactions for individual authors (number of types per author: range 2 to 10 or more). Data on the effect of COI on CPG recommendations were confined to case studies wherein authors with specific financial ties appeared to benefit from the related CPG recommendations. In a single study, few authors believed that their relationships influenced their recommendations. No studies reported on intellectual COI in CPGs.

Conclusions/Significance

There are limited data describing the high prevalence of COI among CPG authors, and only case studies of the effect of COI on CPG recommendations. Further research is needed to explore this potential source of bias.     

Efficacy of cannabinoids against glioblastoma multiforme: A systematic review

IntroductionThe increased incidence of Glioblastoma Multiforme, the most aggressive and most common primary brain tumour, is evident worldwide. Survival rates are reaching only 15 months due to its high recurrence and resistance to current combination therapies including oncotomy, radiotherapy and chemotherapy. Light has been shed in the recent years on the anticancer properties of cannabinoids from Cannabis sativa.ObjectiveTo determine whether cannabinoids alone or in combination with radiotherapy and/or chemotherapy inhibit tumour progression, induce cancer cell death, inhibit metastasis and invasiveness and the mechanisms that underlie these actions.MethodPubMed and Web of Science were used for a systemic search to find studies on the anticancer effects of natural cannabinoids on glioma cancer cells in vitro and/or in vivo.ResultsA total of 302 papers were identified, of which 14 studies were found to fit the inclusion criteria. 5 studies were conducted in vitro, 2 in vivo and 7 were both in vivo and in vitro. 3 studies examined the efficacy of CBD, THC and TMZ, 1 study examined CBD and radiation, 2 studies examined efficacy of THC only and 3 studies examined the efficacy of CBD only. 1 study examined the efficacy of CBD, THC and radiotherapy, 2 studies examined the combination of CBD and THC and 2 more studies examined the efficacy of CBD and TMZ.ConclusionThe evidence in this systematic review leads to the conclusion that cannabinoids possess anticancer potencies against glioma cells, however this effect varies with the combinations and dosages used. Studies so far were conducted on cells in culture and on mice as well as a small number of studies that were conducted on humans. Hence in order to have more accurate results, higher quality studies mainly including human clinical trials with larger sample sizes are necessitated urgently for GBM treatment.     

Future scenarios and life cycle assessment: systematic review and recommendations

The International Journal of Life Cycle Assessment - Future scenarios and life cycle assessment (LCA) are powerful tools that can provide early sustainability assessments of novel products,...     

A systematic review of humoral immune responses against tumor antigens

This review summarizes studies on humoral immune responses against tumor-associated antigens (TAAs) with a focus on antibody frequencies and the potential diagnostic, prognostic, and etiologic relevance of antibodies against TAAs. We performed a systematic literature search in Medline and identified 3,619 articles on humoral immune responses and TAAs. In 145 studies, meeting the inclusion criteria, humoral immune responses in cancer patients have been analyzed against over 100 different TAAs. The most frequently analyzed antigens were p53, MUC1, NY-ESO-1, c-myc, survivin, p62, cyclin B1, and Her2/neu. Antibodies against these TAAs were detected in 0–69% (median 14%) of analyzed tumor patients. Antibody frequencies were generally very low in healthy individuals, with the exception of few TAAs, especially MUC1. For several TAAs, including p53, Her2/neu, and NY-ESO-1, higher antibody frequencies were reported when tumors expressed the respective TAA. Antibodies against MUC1 were associated with a favorable prognosis while antibodies against p53 were associated with poor disease outcome. These data suggest different functional roles of endogenous antibodies against TAAs. Although data on prediagnostic antibody levels are scarce and antibody frequencies for most TAAs are at levels precluding use in diagnostic assays for cancer early detection, there is some promising data on achieving higher sensitivity for cancer detection using panels of TAAs. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Leptospirosis in pregnancy: A systematic review

IntroductionLeptospirosis is a leading zoonotic disease worldwide with more than 1 million cases in the general population per year. With leptospirosis being an emerging infectious disease and as the world’s environment changes with more floods and environmental disasters, the burden of leptospirosis is expected to increase. The objectives of the systematic review were to explore how leptospirosis affects pregnancy, its burden in this population, its effects on maternal and fetal outcomes and the evidence base surrounding treatment options.MethodsWe performed a systematic review of published and unpublished literature using automated and manual methods to screen nine electronic databases since inception, with no language restriction. Two reviewers independently screened articles, completed the data extraction and assessment of risk of bias. Due to significant heterogeneity and paucity of data, we were unable to carry out a meta-analysis, but we conducted a pooled analysis of individual patient data from the case reports and case series to examine the patient and disease characteristics, diagnostic methods, differential diagnoses, antibiotic treatments, and outcomes of leptospirosis in pregnancy. The protocol for this review was registered on the International Prospective Register of Systematic Reviews, PROSPERO: CRD42020151501.ResultsWe identified 419 records, of which we included eight observational studies, 21 case reports, three case series and identified four relevant ongoing studies. Overall the studies were with moderate bias and of ‘fair’ quality. We estimated the incidence of leptospirosis in pregnancy to be 1.3 per 10,000 in women presenting with fever or with jaundice, but this is likely to be higher in endemic areas. Adverse fetal outcomes were found to be more common in pregnant patients who presented in the second trimester compared with patients who presented in the third trimester. There is overlap between how leptospirosis presents in pregnancy and in the general population. There is also overlap between the signs, symptoms and biochemical disturbances associated with leptospirosis in pregnancy and the presentation of pregnancy associated conditions, such as Pre-Eclampsia (PET), Acute Fatty Liver of Pregnancy (AFLP) and HELLP Syndrome (Haemolysis Elevated Liver enzymes Low Platelets). In 94% of identified cases with available data, there was an indicator in the patient history regarding exposure that could have helped include leptospirosis in the clinician’s differential diagnosis. We also identified a range of suitable antibiotic therapies for treating leptospirosis in pregnancy, most commonly used were penicillins.ConclusionThis is the first systematic review of leptospirosis in pregnancy and it clearly shows the need to improve early diagnosis and treatment by asking early, treating early, and reporting well. Ask early—broaden differential diagnoses and ask early for potential leptospirosis exposures and risk factors. Treat early—increase index of suspicion in pregnant patients with fever in endemic areas and combine with rapid field diagnosis and early treatment. Report well—need for more good quality epidemiological studies on leptospirosis in pregnancy and better quality reporting of cases in literature.     

Gram-negative neonatal sepsis in low- and lower-middle-income countries and WHO empirical antibiotic recommendations: A systematic review and meta-analysis

BackgroundNeonatal sepsis is a significant global health issue associated with marked regional disparities in mortality. Antimicrobial resistance (AMR) is a growing concern in Gram-negative organisms, which increasingly predominate in neonatal sepsis, and existing WHO empirical antibiotic recommendations may no longer be appropriate. Previous systematic reviews have been limited to specific low- and middle-income countries. We therefore completed a systematic review and meta-analysis of available data from all low- and lower-middle-income countries (LLMICs) since 2010, with a focus on regional differences in Gram-negative infections and AMR.Methods and findingsAll studies published from 1 January 2010 to 21 April 2021 about microbiologically confirmed bloodstream infections or meningitis in neonates and AMR in LLMICs were assessed for eligibility. Small case series, studies with a small number of Gram-negative isolates (<10), and studies with a majority of isolates prior to 2010 were excluded. Main outcomes were pooled proportions of Escherichia coli, Klebsiella, Enterobacter, Pseudomonas, Acinetobacter and AMR. We included 88 studies (4 cohort studies, 3 randomised controlled studies, and 81 cross-sectional studies) comprising 10,458 Gram-negative isolates from 19 LLMICs. No studies were identified outside of Africa and Asia. The estimated pooled proportion of neonatal sepsis caused by Gram-negative organisms was 60% (95% CI 55% to 65%). Klebsiella spp. was the most common, with a pooled proportion of 38% of Gram-negative sepsis (95% CI 33% to 43%). Regional differences were observed, with higher proportions of Acinetobacter spp. in Asia and Klebsiella spp. in Africa. Resistance to aminoglycosides and third-generation cephalosporins ranged from 42% to 69% and from 59% to 84%, respectively. Study limitations include significant heterogeneity among included studies, exclusion of upper-middle-income countries, and potential sampling bias, with the majority of studies from tertiary hospital settings, which may overestimate the burden caused by Gram-negative bacteria.ConclusionsGram-negative bacteria are an important cause of neonatal sepsis in LLMICs and are associated with significant rates of resistance to WHO-recommended first- and second-line empirical antibiotics. AMR surveillance should underpin region-specific empirical treatment recommendations. Meanwhile, a significant global commitment to accessible and effective antimicrobials for neonates is required.

Sophie Wen and co-workers report a meta-analysis on bacterial isolates and antimicrobial resistance in neonatal sepsis in low- and lower-middle-income countries.     

Methodology matters when estimating deer abundance: a global systematic review and recommendations for improvements

Deer (Cervidae) are key components of many ecosystems and estimating deer abundance or density is important to understanding these roles. Many field methods have been used to estimate deer abundance and density, but the factors determining where, when, and why a method was used, and its usefulness, have not been investigated. We systematically reviewed journal articles published during 2004–2018 to evaluate spatio-temporal trends in study objectives, methodologies, and deer abundance and density estimates, and determine how they varied with biophysical and anthropogenic attributes. We also reviewed the precision and bias of deer abundance estimation methods. We found 3,870 deer abundance and density estimates. Most estimates (58%) were for white-tailed deer (Odocoileus virginianus), red deer (Cervus elaphus), and roe deer (Capreolus capreolus). The 6 key methods used to estimate abundance and density were pedestrian sign (track or fecal) counts, pedestrian direct counts, vehicular direct counts, aerial direct counts, motion-sensitive cameras, and harvest data. There were regional differences in the use of these methods, but a general pattern was a temporal shift from using harvest data, pedestrian direct counts, and aerial direct counts to using pedestrian sign counts and motion-sensitive cameras. Only 32% of estimates were accompanied by a measure of precision. The most precise estimates were from vehicular spotlight counts and from capture–recapture analysis of images from motion-sensitive cameras. For aerial direct counts, capture–recapture methods provided the most precise estimates. Bias was robustly assessed in only 16 studies. Most abundance estimates were negatively biased, but capture–recapture methods were the least biased. The usefulness of deer abundance and density estimates would be substantially improved by 1) reporting key methodological details, 2) robustly assessing bias, 3) reporting the precision of estimates, 4) using methods that increase and estimate detection probability, and 5) staying up to date on new methods. The automation of image analysis using machine learning should increase the accuracy and precision of abundance estimates from direct aerial counts (visible and thermal infrared, including from unmanned aerial vehicles [drones]) and motion-sensitive cameras, and substantially reduce the time and cost burdens of manual image analysis.     

Protection afforded by previous Vibrio cholerae infection against subsequent disease and infection: A review

BackgroundCholera is an acute, diarrheal disease caused by Vibrio cholerae O1 or 139 that is associated with a high global burden.MethodsWe analyzed the estimated duration of immunity following cholera infection from available published studies. We searched PubMed and Web of Science for studies of the long-term immunity following cholera infection. We identified 22 eligible studies and categorized them as either observational, challenge, or serological.ResultsWe found strong evidence of protection at 3 years after infection in observational and challenge studies. However, serological studies show that elevated humoral markers of potential correlates of protection returned to baseline within 1 year. Additionally, a subclinical cholera infection may confer lower protection than a clinical one, as suggested by 3 studies that found that, albeit with small sample sizes, most participants with a subclinical infection from an initial challenge with cholera had a symptomatic infection when rechallenged with a homologous biotype.ConclusionsThis review underscores the need to elucidate potential differences in the protection provided by clinical and subclinical cholera infections. Further, more studies are warranted to bridge the gap between the correlates of protection and cholera immunity. Understanding the duration of natural immunity to cholera can help guide control strategies and policy.     

Vaccination against meningococcal disease in Europe: review and recommendations for the use of conjugate vaccines

At the end of 2005, six European countries had implemented public immunization campaigns with serogroup C conjugate vaccines, and all had experienced substantial declines in the incidence of serogroup C disease. A quadrivalent ACWY meningococcal vaccine is in use in the USA, but serogroup A is extremely rare in Europe and serogroups Y and W135 are infrequent causes of disease. This paper outlines recommendations on the use of conjugate vaccines in Europe based on the experience with meningococcal C conjugate (MCC) vaccines so far.     

Oral manifestations in chikungunya patients: A systematic review

BackgroundChikungunya fever is considered an abrupt onset arbovirus transmitted by mosquitoes, mainly Aedes aegypti and Aedes albopictus. The disease has a significant impact on the quality of life of affected persons, and many of its numerous symptoms have not yet been properly clarified, such as the manifestations that can occur in the oral cavity. The aim of this study was to identify the main oral manifestations related to chikungunya fever, as well as describe the demographic characteristics of patients, by conducting a systematic review of the literature.Methods and findingsSearches were performed in MEDLINE (PubMed), Embase (Elsevier), LILACS (VHL), Cochrane Library, Scopus, and CAPES electronic databases for theses and dissertations published up to January 16, 2021 without language and date restrictions. Additional manual searches of gray literature, reference list, and Google Scholar were carried out. We included 27 studies highlighting mainly oral manifestations that cause masticatory discomfort such as ulcers and oral thrush, gingival bleeding, pain and burning of the oral mucous membranes, temporomandibular joint (TMJ) arthralgia, opportunistic infections, and changes in taste.ConclusionsThere seems to be a predominance of oral manifestations that cause discomfort when chewing, such as ulcerations in the acute phase of the disease, with complete remission within 3 to 10 days after the onset, apparently mostly affecting women and older persons. These oral manifestations can be compatible with basic viral infections related to inflammatory response and transitory immunosuppression.     

Turning evidence into recommendations: Protocol of a study guideline development groups

Background

The Accreditation Council on Graduate Medical Education (ACGME) supports chart audit as a method to track competency in Practice-Based Learning and Improvement. We examined whether peer chart audits performed by internal medicine residents were associated with improved documentation of foot care in patients with diabetes mellitus.

Methods

A retrospective electronic chart review was performed on 347 patients with diabetes mellitus cared for by internal medicine residents in a university-based continuity clinic from May 2003 to September 2004. Residents abstracted information pertaining to documentation of foot examinations (neurological, vascular, and skin) from the charts of patients followed by their physician peers. No formal feedback or education was provided.

Results

Significant improvement in the documentation of foot exams was observed over the course of the study. The percentage of patients receiving neurological, vascular, and skin exams increased by 20% (from 13% to 33%) (p = 0.001), 26% (from 45% to 71%) (p < 0.001), and 18% (51%–72%) (p = 0.005), respectively. Similarly, the proportion of patients receiving a well-documented exam which includes all three components – neurological, vascular and skin foot exam – increased over time (6% to 24%, p < 0.001).

Conclusion

Peer chart audits performed by residents in the absence of formal feedback were associated with improved documentation of the foot exam in patients with diabetes mellitus. Although this study suggests that peer chart audits may be an effective tool to improve practice-based learning and documentation of foot care in diabetic patients, evaluating the actual performance of clinical care was beyond the scope of this study and would be better addressed by a randomized controlled trial.     

Surface electromyography in animal biomechanics: A systematic review

The study of muscle activity using surface electromyography (sEMG) is commonly used for investigations of the neuromuscular system in man. Although sEMG has faced methodological challenges, considerable technical advances have been made in the last few decades. Similarly, the field of animal biomechanics, including sEMG, has grown despite being confronted with often complex experimental conditions. In human sEMG research, standardised protocols have been developed, however these are lacking in animal sEMG. Before standards can be proposed in this population group, the existing research in animal sEMG should be collated and evaluated. Therefore the aim of this review is to systematically identify and summarise the literature in animal sEMG focussing on (1) species, breeds, activities and muscles investigated, and (2) electrode placement and normalisation methods used. The databases PubMed, Web of Science, Scopus, and Vetmed Resource were searched systematically for sEMG studies in animals and 38 articles were included in the final review. Data on methodological quality was collected and summarised. The findings from this systematic review indicate the divergence in animal sEMG methodology and as a result, future steps required to develop standardisation in animal sEMG are proposed.     

Prevalence of neutralising antibodies against SARS-CoV-2 in acute infection and convalescence: A systematic review and meta-analysis

BackgroundIndividuals infected with SARS-CoV-2 develop neutralising antibodies. We investigated the proportion of individuals with SARS-CoV-2 neutralising antibodies after infection and how this proportion varies with selected covariates.Methodology/Principal findingsThis systematic review and meta-analysis examined the proportion of individuals with SARS-CoV-2 neutralising antibodies after infection and how these proportions vary with selected covariates. Three models using the maximum likelihood method assessed these proportions by study group, covariates and individually extracted data (protocol CRD42020208913). A total of 983 reports were identified and 27 were included. The pooled (95%CI) proportion of individuals with neutralising antibodies was 85.3% (83.5–86.9) using the titre cut off >1:20 and 83.9% (82.2–85.6), 70.2% (68.1–72.5) and 54.2% (52.0–56.5) with titres >1:40, >1:80 and >1:160, respectively. These proportions were higher among patients with severe COVID-19 (e.g., titres >1:80, 84.8% [80.0–89.2], >1:160, 74.4% [67.5–79.7]) than those with mild presentation (56.7% [49.9–62.9] and 44.1% [37.3–50.6], respectively) and lowest among asymptomatic infections (28.6% [17.9–39.2] and 10.0% [3.7–20.1], respectively). IgG and neutralising antibody levels correlated poorly.Conclusions/Significance85% of individuals with proven SARS-CoV-2 infection had detectable neutralising antibodies. This proportion varied with disease severity, study setting, time since infection and the method used to measure antibodies.     

Post-stroke infection: A systematic review and meta-analysis

Background  

stroke is the main cause of disability in high-income countries, and ranks second as a cause of death worldwide. Patients with acute stroke are at risk for infections, but reported post-stroke infection rates vary considerably. We performed a systematic review and meta-analysis to estimate the pooled post-stroke infection rate and its effect on outcome.     

Laser-assisted nucleic acid delivery: A systematic review

Gene therapy has become an effective treatment modality for some conditions. Laser light may augment or enhance gene therapy through photomechanical, photothermal, and photochemical. This review examined the evidence base for laser therapy to enhance nucleic acid transfection in mammalian cells. An electronic search of MEDLINE, Scopus, EMBASE, Web of Science, and Google Scholar was performed, covering all available years. The preferred reporting items for systematic reviews and meta-analyses guideline for systematic reviews was used for designing the study and analyzing the results. In total, 49 studies of laser irradiation for nucleic acid delivery were included. Key approaches were optoporation, photomechanical gene transfection, and photochemical internalization. Optoporation is better suited to cells in culture, photomechanical and photochemical approaches appear well suited to in vivo use. Additional studies explored the impact of photothermal for enhancing gene transfection. Each approach has merits and limitations. Augmenting nucleic acid delivery using laser irradiation is a promising method for improving gene therapy. Laser protocols can be non-invasive because of the penetration of desirable wavelengths of light, but it depends on various parameters such as power density, treatment duration, irradiation mode, etc. The current protocols show low efficiency, and there is a need for further work to optimize irradiation parameters.