-
Scientific Reports Jan 2024We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for... (Meta-Analysis)
Meta-Analysis
We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.
Topics: Humans; Etoposide; Methoxsalen; Azathioprine; Melphalan; Busulfan; Neoplasms; Hematologic Neoplasms; Cyclophosphamide; Cyclosporins; Pharmaceutical Preparations
PubMed: 38172159
DOI: 10.1038/s41598-023-50602-6 -
Environment International Oct 2023The World Health Organization is coordinating an international project aimed at systematically reviewing the evidence regarding the association between radiofrequency... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The World Health Organization is coordinating an international project aimed at systematically reviewing the evidence regarding the association between radiofrequency electromagnetic field (RF-EMF) exposure and adverse health effects. Within the project, 6 topics have been prioritized by an expert group, which include reproductive health outcomes.
OBJECTIVES
According to the protocol published in 2021, a systematic review and meta-analyses on the adverse effects of RF-EMF exposure during pregnancy in offspring of experimental animals were conducted.
METHODS
Three electronic databases (PubMed, Scopus and EMF Portal) were last searched on September 8 or 17, 2022. Based on predefined selection criteria, the obtained references were screened by two independent reviewers. Studies were included if they met the following criteria: 1) original, sham controlled experimental study on non-human mammals exposed in utero, published in peer-reviewed journals, 2) the experimental RF-EMF exposure was within the frequency range 100 kHz-300 GHz, 3) the effects of RF-EMF exposure on fecundity (litter size, embryonic/fetal losses), on the offspring health at birth (decrease of weight or length, congenital malformations, changes of sex ratio) or on delayed effects (neurocognitive alterations, female infertility or early-onset cancer) were studied. Study characteristics and outcome data were extracted by two reviewers. Risk of bias (RoB) was assessed using the Office of Health Assessment and Translation (OHAT) guidelines. Study results were pooled in a random effects meta-analysis comparing average exposure to no-exposure and in a dose-response meta-analysis using all exposure doses, after exclusion of studies that were rated at "high concern" for RoB. Subgroup analyses were conducted for species, Specific Absorption Rate (SAR) and temperature increase. The certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.
RESULTS
Eighty-eight papers could be included in this review. Effects on fecundity. The meta-analysis of studies on litter size, conducted at a whole-body average SAR of 4.92 W/kg, did not show an effect of RF-EMF exposure (MD 0.05; 95% CI -0.21 to 0.30). The meta-analysis of studies on resorbed and dead fetuses, conducted at a whole-body average SAR of 20.26 W/kg, showed a significant increase of the incidence in RF-EMF exposed animals (OR 1.84; 95% CI 1.27 to 2.66). The results were similar in the dose-response analysis. Effects on the offspring health at birth. The meta-analysis of studies on fetal weight, conducted at a whole-body average SAR of 9.83 W/kg, showed a small decrease in RF-EMF exposed animals (SMD 0.31; 95% CI 0.15 to 0.48). The meta-analysis of studies on fetal length, conducted at a whole-body average SAR of 4.55 W/kg, showed a moderate decrease in length at birth (SMD 0.45; 95% CI 0.07 to 0.83). The meta-analysis of studies on the percentage of fetuses with malformations, conducted at a whole-body average SAR of 6.75 W/kg, showed a moderate increase in RF-EMF exposed animals (SMD -0.45; 95% CI -0.68 to -0.23). The meta-analysis of studies on the incidence of litters with malformed fetuses, conducted at a whole-body average SAR of 16.63 W/kg, showed a statistically significant detrimental RF-EMF effect (OR 3.22; 95% CI 1.9 to 5.46). The results were similar in the dose-response analyses. Delayed effects on the offspring health. RF-EMF exposure was not associated with detrimental effects on brain weight (SMD 0.10; 95% CI -0.09 to 0.29) and on learning and memory functions (SMD -0.54; 95% CI -1.24 to 0.17). RF-EMF exposure was associated with a large detrimental effect on motor activity functions (SMD 0.79; 95% CI 0.21 to 1.38) and a moderate detrimental effect on motor and sensory functions (SMD -0.66; 95% CI -1.18 to -0.14). RF-EMF exposure was not associated with a decrease of the size of litters conceived by F2 female offspring (SMD 0.08; 95% CI -0.39 to 0.55). Notably, meta-analyses of neurobehavioural effects were based on few studies, which suffered of lack of independent replication deriving from only few laboratories.
DISCUSSION
There was high certainty in the evidence for a lack of association of RF-EMF exposure with litter size. We attributed a moderate certainty to the evidence of a small detrimental effect on fetal weight. We also attributed a moderate certainty to the evidence of a lack of delayed effects on the offspring brain weight. For most of the other endpoints assessed by the meta-analyses, detrimental RF-EMF effects were shown, however the evidence was attributed a low or very low certainty. The body of evidence had limitations that did not allow an assessment of whether RF-EMF may affect pregnancy outcomes at exposure levels below those eliciting a well-known adverse heating impact. In conclusion, in utero RF-EMF exposure does not have a detrimental effect on fecundity and likely affects offspring health at birth, based on the meta-analysis of studies in experimental mammals on litter size and fetal weight, respectively. Regarding possible delayed effects of in utero exposure, RF-EMF probably does not affect offspring brain weight and may not decrease female offspring fertility; on the other hand, RF-EMF may have a detrimental impact on neurobehavioural functions, varying in magnitude for different endpoints, but these last findings are very uncertain. Further research is needed on the effects at birth and delayed effects with sample sizes adequate for detecting a small effect. Future studies should use standardized endpoints for testing prenatal developmental toxicity and developmental neurotoxicity (OECD TG 414 and 426), improve the description of the exposure system design and exposure conditions, conduct appropriate dosimetry characterization, blind endpoint analysis and include several exposure levels to better enable the assessment of a dose-response relationship.
PROTOCOL REGISTRATION AND PUBLICATION
The protocol was published in Pacchierotti et al., 2021 and registered in PROSPERO CRD42021227746 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=227746).
Topics: Pregnancy; Animals; Female; Electromagnetic Fields; Fetal Weight; Reproduction; Fertility; Mammals
PubMed: 37729852
DOI: 10.1016/j.envint.2023.108178 -
Journal of Ethnopharmacology Nov 2021'Akebia stem' (Akebiae caulis) is one of the newest raw materials officially introduced into therapeutic practice from traditional Chinese medicine. A monograph on this... (Comparative Study)
Comparative Study
ETHNOPHARMACOLOGICAL RELEVANCE
'Akebia stem' (Akebiae caulis) is one of the newest raw materials officially introduced into therapeutic practice from traditional Chinese medicine. A monograph on this material appeared for the first time in 2018 in Supplement 9.6 to the 9th edition of the European Pharmacopoeia. In the latest 10th edition of the European Pharmacopoeia, the monograph remained unchanged. The 'Akebia stem' monograph allows the use, as a raw material, of Akebia quinata (Houtt.) Decne., A. trifoliata (Thunb.) Koidz, or a mixture of the two species.
AIM OF THE STUDY
The aim of this work is a detailed review of the scientific literature on the genus Akebia (family Lardizabalaceae), with particular emphasis on A. quinata and A. trifoliata, providing information on the botanical, ecological, and chemical characteristics of these species. Professional research on their biological activity has been reviewed. The attention is given to phytochemistry and cosmetology. The traditional use of Akebia species and their potential use in medicine and cosmetology are assessed. In addition, individual papers describing biotechnology research on in vitro cultures of the two Akebia species are presented.
MATERIALS AND METHODS
The presented botanical, ecological, phytochemical and biotechnological characterization is based on a thorough review of published scientific research. It is a compilation and evaluation of data on the chemical composition and biological activities of these Akebia species.
RESULTS
This critical review of phytochemical studies demonstrates that triterpenoid saponins are dominant secondary metabolites of these species. A comparative analysis of phytochemical studies on A. quinata and A. trifoliata stems, roots, fruits, and seeds showed differences in metabolites based on the plant parts and species. The triterpenoid saponins mutongsaponin C and saponin P have been found only in A. trifoliata, whereas the phenolic glycoside 2-(3,4-dihydroxyphenyl)-ethyl-O-β-D-glucopyranoside has been found only in A. quinata. Biological activity studies of A. quinata stem, leaf and/or fruit extracts have confirmed diuretic, hepatoregenerative, neuroprotective, analgesic, anti-inflammatory, and anti-obesity effects and an influence on ethanol metabolism. Different action profiles have been demonstrated for A. trifoliata stem, leaf and/or fruit extracts. Studies have proven the antibacterial and anticancer (liver and stomach) effects of these species. This review presents potential phytopharmacological applications of both species and detailed data on their broad applications in cosmetology. Attention is also drawn to information on the safety of using Akebia. Finally, an overview of biotechnology research on both species is presented.
CONCLUSIONS
This review provides comprehensive knowledge about the ethnopharmacological use of Akebia species. Moreover, new findings on the differences in the chemical composition and biological activity profiles are underlined.
Topics: Animals; Biotechnology; Cosmetics; Drugs, Chinese Herbal; Ethnopharmacology; Humans; Phytochemicals; Ranunculales
PubMed: 34352331
DOI: 10.1016/j.jep.2021.114486 -
Chinese Medicine 2019In China, the medical use of fecal matter (fresh fecal suspension or dry feces) can be dated back to the fourth century, approximately 1700 years ago. In long-term... (Review)
Review
In China, the medical use of fecal matter (fresh fecal suspension or dry feces) can be dated back to the fourth century, approximately 1700 years ago. In long-term clinical practice, Chinese doctors have accumulated unique and invaluable medical experience in the use of fecal materials. In view of their good curative effect and medicinal potential, fecal medicines should be paid much attention. This study aimed to provide the first comprehensive data compilation of fecal medicines used in various Chinese traditional medical systems by bibliographic investigation of 31 medicine monographs and standards. A total of 54 fecal medicines were found to be used in 14 traditional Chinese medical systems. Their names, original species, medicinal forms, and traditional uses were described in detail. These fecal medicines were commonly used to treat gastrointestinal, nervous system, skin, and gynecological diseases. Commonly used fecal medicines include Wu-Ling-Zhi, Jiu-Fen and Hei-Bing-Pian. The information summarized in this study can provide a good reference for the development and utilization of fecal medicines. Further studies are necessary to prove their medicinal value, identify their active ingredients, and elucidate their mechanisms of action so that more people can accept these special medicines.
PubMed: 31528199
DOI: 10.1186/s13020-019-0253-x -
Journal of the National Cancer... Jul 2020Ionizing radiation is an established carcinogen, but risks from low-dose exposures are controversial. Since the Biological Effects of Ionizing Radiation VII review of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ionizing radiation is an established carcinogen, but risks from low-dose exposures are controversial. Since the Biological Effects of Ionizing Radiation VII review of the epidemiological data in 2006, many subsequent publications have reported excess cancer risks from low-dose exposures. Our aim was to systematically review these studies to assess the magnitude of the risk and whether the positive findings could be explained by biases.
METHODS
Eligible studies had mean cumulative doses of less than 100 mGy, individualized dose estimates, risk estimates, and confidence intervals (CI) for the dose-response and were published in 2006-2017. We summarized the evidence for bias (dose error, confounding, outcome ascertainment) and its likely direction for each study. We tested whether the median excess relative risk (ERR) per unit dose equals zero and assessed the impact of excluding positive studies with potential bias away from the null. We performed a meta-analysis to quantify the ERR and assess consistency across studies for all solid cancers and leukemia.
RESULTS
Of the 26 eligible studies, 8 concerned environmental, 4 medical, and 14 occupational exposure. For solid cancers, 16 of 22 studies reported positive ERRs per unit dose, and we rejected the hypothesis that the median ERR equals zero (P = .03). After exclusion of 4 positive studies with potential positive bias, 12 of 18 studies reported positive ERRs per unit dose (P = .12). For leukemia, 17 of 20 studies were positive, and we rejected the hypothesis that the median ERR per unit dose equals zero (P = .001), also after exclusion of 5 positive studies with potential positive bias (P = .02). For adulthood exposure, the meta-ERR at 100 mGy was 0.029 (95% CI = 0.011 to 0.047) for solid cancers and 0.16 (95% CI = 0.07 to 0.25) for leukemia. For childhood exposure, the meta-ERR at 100 mGy for leukemia was 2.84 (95% CI = 0.37 to 5.32); there were only two eligible studies of all solid cancers.
CONCLUSIONS
Our systematic assessments in this monograph showed that these new epidemiological studies are characterized by several limitations, but only a few positive studies were potentially biased away from the null. After exclusion of these studies, the majority of studies still reported positive risk estimates. We therefore conclude that these new epidemiological studies directly support excess cancer risks from low-dose ionizing radiation. Furthermore, the magnitude of the cancer risks from these low-dose radiation exposures was statistically compatible with the radiation dose-related cancer risks of the atomic bomb survivors.
Topics: Adult; Bias; Child; Epidemiologic Studies; Humans; Neoplasms, Radiation-Induced; Occupational Exposure; Radiation Dosage; Radiation, Ionizing
PubMed: 32657347
DOI: 10.1093/jncimonographs/lgaa010 -
BMC Gastroenterology Mar 2021There is increased interest in the therapeutic use of statins in cirrhosis, but preferred statin and safety outcomes are still not well known. In this systematic review...
BACKGROUND/AIMS
There is increased interest in the therapeutic use of statins in cirrhosis, but preferred statin and safety outcomes are still not well known. In this systematic review we aimed to address pharmacokinetics (PK), safety, and effects on cardiovascular (CV) outcomes of statins in cirrhosis.
METHODS
Our systematic search in several electronic databases and repositories of two regulatory bodies up to 2020-06-11 yielded 22 articles and 2 drug monographs with relevant data.
RESULTS
Rosuvastatin and pitavastatin showed minimal PK changes in Child-Pugh A cirrhosis. Only rosuvastatin was assessed in a repeated dosing PK study. Atorvastatin showed pronounced PK changes in cirrhosis. No PK data was found for simvastatin, the most commonly used statin in cirrhosis trials. There was insufficient data to assess CV effects of statins in cirrhosis. Clinical trials in cirrhosis were limited to simvastatin, atorvastatin, and pravastatin. In patients taking simvastatin 40 mg, pooled frequency of rhabdomyolysis was 2%, an incidence 40-fold higher than that reported in non-cirrhosis patients, while this was no rhabdomyolysis observed in patients on simvastatin 20 mg, atorvastatin 20 mg, or pravastatin 40 mg. Drug-induced liver injury was of difficult interpretation due to co-existence of muscle damage. No overt liver failure was reported.
CONCLUSIONS
Simvastatin 40 mg should be avoided in decompensated cirrhosis. Safety data on simvastatin 20 mg or other statins are based on small study sample size. This rarity of evidence combined with lack of data in dose adjustment methods in cirrhosis is a barrier for using statins for CV indications or for investigational use for liver indications.
Topics: Atorvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver Cirrhosis; Pravastatin; Simvastatin
PubMed: 33726685
DOI: 10.1186/s12876-021-01704-w -
BMC Cancer Mar 2021Although myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) - including chronic myeloid leukemia (CML) - and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Although myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) - including chronic myeloid leukemia (CML) - and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are largely clinically distinct myeloid malignancies, epidemiological studies rarely examine them separately and often combine them with lymphoid malignancies, limiting possible etiological interpretations for specific myeloid malignancies.
METHODS
We systematically evaluated the epidemiological literature on the four chemical agents (1,3-butadiene, formaldehyde, benzene, and tobacco smoking, excluding pharmaceutical, microbial and radioactive agents, and pesticides) classified by the International Agency for Research on Cancer as having sufficient epidemiological evidence to conclude that each causes "myeloid malignancies." Literature searches of IARC Monographs and PubMed identified 85 studies that we critically assessed, and for appropriate subsets, summarized results using meta-analysis.
RESULTS
Only two epidemiological studies on 1,3-butadiene were identified, but reported findings were inadequate to evaluate specific myeloid malignancies. Studies on formaldehyde reported results for AML and CML - and not for MDS or MPN - but reported no increased risks. For benzene, several specific myeloid malignancies were evaluated, with consistent associations reported with AML and MDS and mixed results for CML. Studies of tobacco smoking examined all major myeloid malignancies, demonstrating consistent relationships with AML, MDS and MPN, but not with CML.
CONCLUSIONS
Surprisingly few epidemiological studies present results for specific myeloid malignancies, and those identified were inconsistent across studies of the same exposure, as well as across chemical agents. This exercise illustrates that even for agents classified as having sufficient evidence of causing "myeloid malignancies," the epidemiological evidence for specific myeloid malignancies is generally limited and inconsistent. Future epidemiological studies should report findings for the specific myeloid malignancies, as combining them post hoc - where appropriate - always remains possible, whereas disaggregation may not. Furthermore, combining results across possibly discrete diseases reduces the chances of identifying important malignancy-specific causal associations.
Topics: Carcinogens, Environmental; Causality; Epidemiologic Studies; Humans; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Myeloproliferative Disorders
PubMed: 33676443
DOI: 10.1186/s12885-021-07908-3 -
Human & Experimental Toxicology 2022There are hereditary types of nephroblastoma or Wilms' tumor associated with exposure of the germ cells of either parent to harmful environmental factors. Some studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There are hereditary types of nephroblastoma or Wilms' tumor associated with exposure of the germ cells of either parent to harmful environmental factors. Some studies have examined the exposure of compounds used pesticides and herbicides as a risk factor for Wilms' tumor.
METHODS
A systematic review and meta-analysis were carried out on case-control studies to establish the potential link between exposure to these organic molecules and Wilms' tumor occurrence in children rigorously. We examined the monographs on some organo-phosphate insecticides and herbicides issued by the International Association for the Research on Cancer (IARC) under the auspices of the World Health Organization (WHO). PUBMED, SCOPUS, and Google Scholar studies (1960-2021) were identified and systematically reviewed following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Subgroup analyses were conducted after stratification for occupational versus residential exposure and before birth (prenatal) vs. after birth (postnatal) exposure. In addition, we revised the monographs on chemical compounds issued recently by the IARC/WHO.
RESULTS
Our findings seem to consolidate that parental pesticide exposure during the preconception or pregnancy period is correlated with an increased occurrence risk for Wilms' tumor. We confirm the validity of the WHO essays on certain organophosphate herbicides and insecticides, which support these compounds, may be highly relevant in future cancer prevention policies.
CONCLUSION
Parental exposure to pesticides, particularly in household settings, is poorly emphasized in our society. There is a strong association between these organophosphate compounds and pediatric cancer. Public health agencies may need to take stronger action than in the past.
Topics: Child; Pregnancy; Female; Humans; Pesticides; Kidney Neoplasms; Insecticides; Wilms Tumor; Parents; World Health Organization; Herbicides; Organophosphates
PubMed: 36289056
DOI: 10.1177/09603271221136211 -
Environmental Health Perspectives Nov 2023There is a long tradition in environmental health of using frameworks for evidence synthesis, such as those of the U.S. Environmental Protection Agency for its...
BACKGROUND
There is a long tradition in environmental health of using frameworks for evidence synthesis, such as those of the U.S. Environmental Protection Agency for its Integrated Science Assessments and the International Agency for Research on Cancer Monographs. The framework, Grading of Recommendations Assessment, Development, and Evaluation (GRADE), was developed for evidence synthesis in clinical medicine. The U.S. Office of Health Assessment and Translation (OHAT) elaborated an approach for evidence synthesis in environmental health building on GRADE.
METHODS
We applied a modified OHAT approach and a broader "narrative" assessment to assess the level of confidence in a large systematic review on traffic-related air pollution and health outcomes.
DISCUSSION
We discuss several challenges with the OHAT approach and its implementation and suggest improvements for synthesizing evidence from observational studies in environmental health. We consider the determination of confidence using a formal rating scheme of up- and downgrading of certain factors, the treatment of every factor as equally important, and the lower initial confidence rating of observational studies to be fundamental issues in the OHAT approach. We argue that some observational studies can offer high-confidence evidence in environmental health. We note that heterogeneity in magnitude of effect estimates should generally not weaken the confidence in the evidence, and consistency of associations across study designs, populations, and exposure assessment methods may strengthen confidence in the evidence. We mention that publication bias should be explored beyond statistical methods and is likely limited when large and collaborative studies comprise most of the evidence and when accrued over several decades. We propose to identify possible key biases, their most likely direction, and their potential impacts on the results. We think that the OHAT approach and other GRADE-type frameworks require substantial modification to align better with features of environmental health questions and the studies that address them. We emphasize that a broader, "narrative" evidence assessment based on the systematic review may complement a formal GRADE-type evaluation. https://doi.org/10.1289/EHP11532.
Topics: Air Pollution; Environmental Health; Research Design; Observational Studies as Topic
PubMed: 37991444
DOI: 10.1289/EHP11532 -
The Cochrane Database of Systematic... Jul 2020Printed educational materials are widely used dissemination strategies to improve the quality of healthcare professionals' practice and patient health outcomes.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Printed educational materials are widely used dissemination strategies to improve the quality of healthcare professionals' practice and patient health outcomes. Traditionally they are presented in paper formats such as monographs, publication in peer-reviewed journals and clinical guidelines. This is the fourth update of the review.
OBJECTIVES
To assess the effect of printed educational materials (PEMs) on the practice of healthcare professionals and patient health outcomes. To explore the influence of some of the characteristics of the printed educational materials (e.g. source, content, format) on their effect on healthcare professionals' practice and patient health outcomes.
SEARCH METHODS
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), HealthStar, CINAHL, ERIC, CAB Abstracts, Global Health, and EPOC Register from their inception to 6 February 2019. We checked the reference lists of all included studies and relevant systematic reviews.
SELECTION CRITERIA
We included randomised trials (RTs), controlled before-after studies (CBAs) and interrupted time series studies (ITSs) that evaluated the impact of PEMs on healthcare professionals' practice or patient health outcomes. We included three types of comparisons: (1) PEM versus no intervention, (2) PEM versus single intervention, (3) multifaceted intervention where PEM is included versus multifaceted intervention without PEM. Any objective measure of professional practice (e.g. prescriptions for a particular drug), or patient health outcomes (e.g. blood pressure) were included.
DATA COLLECTION AND ANALYSIS
Two reviewers undertook data extraction independently. Disagreements were resolved by discussion. For analyses, we grouped the included studies according to study design, type of outcome and type of comparison. For controlled trials, we reported the median effect size for each outcome within each study, the median effect size across outcomes for each study and the median of these effect sizes across studies. Where data were available, we re-analysed the ITS studies by converting all data to a monthly basis and estimating the effect size from the change in the slope of the regression line between before and after implementation of the PEM. We reported median changes in slope for each outcome, for each study, and then across studies. We standardised all changes in slopes by their standard error, allowing comparisons and combination of different outcomes. We categorised each PEM according to potential effects modifiers related to the source of the PEMs, the channel used for their delivery, their content, and their format. We assessed the risks of bias of all the included studies.
MAIN RESULTS
We included 84 studies: 32 RTs, two CBAs and 50 ITS studies. Of the 32 RTs, 19 were cluster RTs that used various units of randomisation, such as practices, health centres, towns, or areas. The majority of the included studies (82/84) compared the effectiveness of PEMs to no intervention. Based on the RTs that provided moderate-certainty evidence, we found that PEMs distributed to healthcare professionals probably improve their practice, as measured with dichotomous variables, compared to no intervention (median absolute risk difference (ARD): 0.04; interquartile range (IQR): 0.01 to 0.09; 3,963 healthcare professionals randomised within 3073 units). We could not confirm this finding using the evidence gathered from continuous variables (standardised mean difference (SMD): 0.11; IQR: -0.16 to 0.52; 1631 healthcare professionals randomised within 1373 units ), from the ITS studies (standardised median change in slope = 0.69; 35 studies), or from the CBA study because the certainty of this evidence was very low. We also found, based on RTs that provided moderate-certainty evidence, that PEMs distributed to healthcare professionals probably make little or no difference to patient health as measured using dichotomous variables, compared to no intervention (ARD: 0.02; IQR: -0.005 to 0.09; 935,015 patients randomised within 959 units). The evidence gathered from continuous variables (SMD: 0.05; IQR: -0.12 to 0.09; 6,737 patients randomised within 594 units) or from ITS study results (standardised median change in slope = 1.12; 8 studies) do not strengthen these findings because the certainty of this evidence was very low. Two studies (a randomised trial and a CBA) compared a paper-based version to a computerised version of the same PEM. From the RT that provided evidence of low certainty, we found that PEM in computerised versions may make little or no difference to professionals' practice compared to PEM in printed versions (ARD: -0.02; IQR: -0.03 to 0.00; 139 healthcare professionals randomised individually). This finding was not strengthened by the CBA study that provided very low certainty evidence (SMD: 0.44; 32 healthcare professionals). The data gathered did not allow us to conclude which PEM characteristics influenced their effectiveness. The methodological quality of the included studies was variable. Half of the included RTs were at risk of selection bias. Most of the ITS studies were conducted retrospectively, without prespecifying the expected effect of the intervention, or acknowledging the presence of a secular trend.
AUTHORS' CONCLUSIONS
The results of this review suggest that, when used alone and compared to no intervention, PEMs may slightly improve healthcare professionals' practice outcomes and patient health outcomes. The effectiveness of PEMs compared to other interventions, or of PEMs as part of a multifaceted intervention, is uncertain.
Topics: Analysis of Variance; Controlled Before-After Studies; Diffusion of Innovation; Information Dissemination; Interrupted Time Series Analysis; Manuals as Topic; Outcome and Process Assessment, Health Care; Periodicals as Topic; Practice Guidelines as Topic; Practice Patterns, Physicians'; Professional Practice; Quality Improvement; Randomized Controlled Trials as Topic; Time Factors
PubMed: 32748975
DOI: 10.1002/14651858.CD004398.pub4