Malignant transformation of oral leukoplakia: Systematic review and comprehensive meta-analysis.

Pimenta-Barros LA ，Ramos-García P ，González-Moles MÁ ，Aguirre-Urizar JM ，Warnakulasuriya S ... -  《-》

Malignant transformation of proliferative Verrucous Leukoplakia-systematic review & meta-analysis.

Proliferative Verrucous Leukoplakia (PVL) presents a unique manifestation of Oral Leukoplakia, characterized by its notable propensity for rapid advancement, dynamic clinical and histopathological alterations, and heightened risk of malignant transformation. The present systematic review explores the demographic characteristics, risk factors, progression patterns, treatment preferences, and outcomes for PVL lesions that undergo malignant transformation. An electronic search was executed across various databases, such as PubMed, Scopus, Science Direct, Web of Science and Wiley Online Library from 1985 to December 2023, focusing on studies of PVL malignant transformation. Data on demographics, clinical features, treatment, and outcome data were synthesized, with bias assessed using Joanna Briggs Institute Criteria and outcomes evaluated using Comprehensive Meta-Analysis version (CMA) 3.0 software. Among 998 articles, 53 met inclusion criteria, covering 1159 PVL patients, with 48.4% experiencing malignant transformation over an average 6.28 ± 3.73-year follow-up. Most cases had low or moderate bias risk. In the malignant group, females comprised 74.3% of cases, with a mean age of 66.23 ± 7.76 years and had a 1.96 times greater risk of developing cancer (OR 1.96, 95% CI 1.38-2.782; p = 0.001). Gingiva (20%) and gingiva/buccal mucosa (17.4%) were commonly affected. Tobacco and alcohol showed weak associations, with most patients being non-smokers (59.54%) and non-drinkers (78.18%). HPV and candida infection positivity were tested in only a few studies and noted in a limited number of cases (33.3% and 38.46%, respectively). Malignant transformation mainly was invasive carcinoma (86.8%). Surgery was the primary treatment (58.33%), with 55.56% recurrence in 162 cases of data availability on recurrence. Of 228 patients with data availability, 33.77% succumbed to oral cancer from PVL-related oral cancer. PVL, a rare variant of leukoplakia, poses a significant risk of cancer, emphasizing the need for vigilant monitoring and proactive treatment. It mainly affects elderly females without typical cancer risk factors. Understanding its etiology could aid early detection and management.

Mohideen K ，Ghosh S ，Krithika C ，Ali-Hassan M ，Chole R ，Dhungel S ... -  《BMC Oral Health》

Treatment for women with postpartum iron deficiency anaemia.

Postpartum iron deficiency anaemia is caused by antenatal iron deficiency or excessive blood loss at delivery and might affect up to 50% of labouring women in low- and middle-income countries. Effective and safe treatment during early motherhood is important for maternal well-being and newborn care. Treatment options include oral iron supplementation, intravenous iron, erythropoietin, and red blood cell transfusion. To assess the benefits and harms of the available treatment modalities for women with postpartum iron deficiency anaemia. These include intravenous iron, oral iron supplementation, red blood cell transfusion, and erythropoietin. A Cochrane Information Specialist searched for all published, unpublished, and ongoing trials, without language or publication status restrictions. We searched databases including CENTRAL, MEDLINE, Embase, CINAHL, LILACS, WHO ICTRP, and ClinicalTrials.gov, together with reference checking, citation searching, and contact with study authors to identify eligible studies. We applied date limits to retrieve new records since the last search on 9 April 2015 until 11 April 2024. We included published, unpublished, and ongoing randomised controlled trials (RCTs) that compared treatments for postpartum iron deficiency anaemia with placebo, no treatment, or alternative treatments. Cluster-randomised trials were eligible for inclusion. We included RCTs regardless of blinding. Participants were women with postpartum haemoglobin ≤ 12 g/dL, treated within six weeks after childbirth. We excluded non-randomised, quasi-randomised, and cross-over trials. The critical outcomes of this review were maternal mortality and fatigue. The important outcomes included persistent anaemia symptoms, persistent postpartum anaemia, psychological well-being, infections, compliance with treatment, breastfeeding, length of hospital stay, serious adverse events, anaphylaxis or evidence of hypersensitivity, flushing/Fishbane reaction, injection discomfort/reaction, constipation, gastrointestinal pain, number of red blood cell transfusions, and haemoglobin levels. We assessed risk of bias in the included studies using the Cochrane RoB 1 tool. Two review authors independently performed study screening, risk of bias assessment, and data extraction. We contacted trial authors for supplementary data when necessary. We screened all trials for trustworthiness and scientific integrity using the Cochrane Trustworthiness Screening Tool. We conducted meta-analyses using a fixed-effect model whenever feasible to synthesise outcomes. In cases where data were not suitable for meta-analysis, we provided a narrative summary of important findings. We evaluated the overall certainty of the evidence using GRADE. We included 33 RCTs with a total of 4558 postpartum women. Most trials were at high risk of bias for several risk of bias domains. Most of the evidence was of low or very low certainty. Imprecision due to few events and risk of bias due to lack of blinding were the most important factors. Intravenous iron versus oral iron supplementation The evidence is very uncertain about the effect of intravenous iron on mortality (risk ratio (RR) 2.95, 95% confidence interval (CI) 0.12 to 71.96; P = 0.51; I² = not applicable; 3 RCTs; 1 event; 572 women; very low-certainty evidence). One woman died of cardiomyopathy, and another developed arrhythmia, both in the groups treated with intravenous iron. Intravenous iron probably results in a slight reduction in fatigue within 8 to 28 days (standardised mean difference -0.25, 95% CI -0.42 to -0.07; P = 0.006; I² = 47%; 2 RCTs; 515 women; moderate-certainty evidence). Breastfeeding was not reported. Oral iron probably increases the risk of constipation compared to intravenous iron (RR 0.12, 95% CI 0.06 to 0.21; P < 0.001; I² = 0%; 10 RCTs; 1798 women; moderate-certainty evidence). The evidence is very uncertain about the effect of intravenous iron on anaphylaxis or hypersensitivity (RR 2.77, 95% CI 0.31 to 24.86; P = 0.36; I² = 0%; 12 RCTs; 2195 women; very low-certainty evidence). Three women treated with intravenous iron experienced anaphylaxis or hypersensitivity. The trials that reported on haemoglobin at 8 to 28 days were too heterogeneous to pool. However, 5 of 6 RCTs favoured intravenous iron, with mean changes in haemoglobin ranging from 0.73 to 2.10 g/dL (low-certainty evidence). Red blood cell transfusion versus intravenous iron No women died in the only trial that reported on mortality (1 RCT; 7 women; very low-certainty evidence). The evidence is very uncertain about the effect of red blood cell transfusion on fatigue at 8 to 28 days (mean difference (MD) 1.20, 95% CI -2.41 to 4.81; P = 0.51; I² = not applicable; 1 RCT; 13 women; very low-certainty evidence) and breastfeeding more than six weeks postpartum (RR 0.43, 95% CI 0.12 to 1.57; P = 0.20; I² = not applicable; 1 RCT; 13 women; very low-certainty evidence). Constipation and anaphylaxis were not reported. Red blood cell transfusion may result in little to no difference in haemoglobin within 8 to 28 days (MD -1.00, 95% CI -2.02 to 0.02; P = 0.05; I² = not applicable; 1 RCT; 12 women; low-certainty evidence). Intravenous iron and oral iron supplementation versus oral iron supplementation Mortality and breastfeeding were not reported. One trial reported a greater improvement in fatigue in the intravenous and oral iron group, but the effect size could not be calculated (1 RCT; 128 women; very low-certainty evidence). Intravenous iron and oral iron may result in a reduction in constipation compared to oral iron alone (RR 0.21, 95% CI 0.07 to 0.69; P = 0.01; I² = not applicable; 1 RCT; 128 women; low-certainty evidence). There were no anaphylaxis or hypersensitivity events in the trials (2 RCTs; 168 women; very low-certainty evidence). Intravenous iron and oral iron may result in little to no difference in haemoglobin (g/dL) at 8 to 28 days (MD 0.00, 95% CI -0.48 to 0.48; P = 1.00; I² = not applicable; 1 RCT; 60 women; low-certainty evidence). Red blood cell transfusion versus no transfusion Mortality, fatigue at day 8 to 28, constipation, anaphylaxis, and haemoglobin were not reported. Red blood cell transfusion may result in little to no difference in breastfeeding more than six weeks postpartum (RR 0.91, 95% CI 0.78 to 1.07; P = 0.24; I² = not applicable; 1 RCT; 297 women; low-certainty evidence). Oral iron supplementation versus placebo or no treatment Mortality, fatigue, breastfeeding, constipation, anaphylaxis, and haemoglobin were not reported. Two trials reported on gastrointestinal symptoms, but did not report results by study arm. Intravenous iron probably reduces fatigue slightly in the early postpartum weeks (8 to 28 days) compared to oral iron tablets, but probably results in little to no difference after four weeks. It is very uncertain if intravenous iron has an effect on mortality and anaphylaxis/hypersensitivity. Breastfeeding was not reported. Intravenous iron may increase haemoglobin slightly more than iron tablets, but the data were too heterogeneous to pool. However, changes in haemoglobin levels are a surrogate outcome, and treatment decisions should preferentially be based on patient-relevant outcomes. Iron tablets probably result in a large increase in constipation compared to intravenous iron. The effect of red blood cell transfusion compared to intravenous iron on mortality, fatigue, and breastfeeding is very uncertain. No studies reported on constipation or anaphylaxis/hypersensitivity. Red blood cell transfusion may result in little to no difference in haemoglobin at 8 to 28 days. The effect of intravenous iron and oral iron supplementation on mortality, fatigue, breastfeeding, and anaphylaxis/hypersensitivity is very uncertain or unreported. Intravenous iron and oral iron may result in a reduction in constipation compared to oral iron alone, and in little to no difference in haemoglobin. The effect of red blood cell transfusion compared to non-transfusion on mortality, fatigue, constipation, anaphylaxis/hypersensitivity, and haemoglobin is unreported. Red blood cell transfusion may result in little to no difference in breastfeeding. The effect of oral iron supplementation on mortality, fatigue, breastfeeding, constipation, anaphylaxis/hypersensitivity, and haemoglobin is unreported. This Cochrane review had no dedicated funding. Protocol and previous versions are available: Protocol (2013) [DOI: 10.1002/14651858.CD010861] Original review (2004) [DOI: 10.1002/14651858.CD004222.pub2] Review update (2015) [DOI: 10.1002/14651858.CD010861.pub2].

Jensen MCH ，Holm C ，Jørgensen KJ ，Schroll JB ... -  《Cochrane Database of Systematic Reviews》

The effect of exposure to radiofrequency fields on cancer risk in the general and working population: A systematic review of human observational studies - Part II: Less researched outcomes.

In the framework of the World Health Organization assessment of health effects of exposure to radiofrequency electromagnetic fields (RF-EMF), we have conducted a systematic review of human observational studies on the association between exposure to RF-EMF and risk of neoplastic diseases. Due to the extremely large number of included exposure types/settings and neoplasm combinations, we decided to present the review findings in two separate papers. In the first one we addressed the most investigated exposure-outcome pairs (e.g. glioma, meningioma, acoustic neuroma in relation to mobile phone use, or risk childhood leukemia in relation to environmental exposure from fixed-site transmitters) (Karipidis et al., 2024). Here, we report on less researched neoplasms, which include lymphohematopoietic system tumours, thyroid cancer and oral cavity/pharynx cancer, in relation to wireless phone use, or occupational RF exposure. Eligibility criteria: We included cohort and case-control studies of neoplasia risks in relation to three types of exposure to RF-EMF: 1. exposure from wireless phone use; 2. environmental exposure from fixed-site transmitters; 3. occupational exposures. In the current paper, we focus on less researched neoplasms including leukaemia, non-Hodgkin's lymphoma and thyroid cancer in mobile phone users; lymphohematopoietic system tumours and oral cavity/pharynx cancer in exposed workers. We focussed on investigations of specific neoplasms in relation to specific exposure sources (termed exposure-outcome pair, abbreviated E-O pairs), noting that a single article may address multiple E-O pairs. Eligible studies were identified by predefined literature searches through Medline, Embase, and EMF-Portal. Risk-of-bias (RoB) assessment: We used a tailored version of the Office of Health Assessment and Translation (OHAT) RoB tool to evaluate each study's internal validity. Then, the studies were classified into three tiers according to their overall potential for bias (low, moderate and high) in selected, predefined and relevant bias domains. We synthesized the study results using random effects restricted maximum likelihood (REML) models. Evidence assessment: Confidence in evidence was assessed according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We included 26 articles, which were published between 1988 and 2019, with participants from 10 countries, reporting on 143 different E-O pairs, including 65 different types of neoplasms. Of these, 19 E-O pairs satisfied the criteria for inclusion in quantitative syntheses of the evidence regarding the risks of leukaemia, non-Hodgkin's lymphoma or thyroid cancer in relation to mobile phone use, and the risks of lymphohematopoietic system tumours or oral cavity/pharynx cancer following occupational exposure to RF-EMF. RF-EMF exposure from mobile phones (ever or regular use vs no or non-regular use) was not associated with an increased risk of leukaemia [meta-estimate of the relative risk (mRR) = 0.99, 95 % CI 0.91-1.07, 4 studies), non-Hodgkin's lymphoma (mRR = 0.99, 95 % CI = 0.92-1.06, 5 studies), or thyroid cancer (mRR = 1.05, 95 % CI = 0.88-1.26, 3 studies). Long-term (10 + years) mobile phone use was also not associated with risk of leukaemia (mRR = 1.03, 95 % CI 0.85-1.24, 3 studies), non-Hodgkin lymphoma (mRR = 0.99, 95 % CI 0.86-1.15, 3 studies), or thyroid cancer (no pooled estimate given the small number of studies). There were not sufficient studies of any specific neoplasms to perform dose-response meta-analyses for either cumulative call time or cumulative number of calls; individual studies did not show statistically significant associations between lifetime intensity of mobile phone use and any specific neoplasm. Occupational RF-EMF exposure (exposed vs unexposed) was not associated with an increased risk of lymphohematopoietic system tumours (mRR = 1.03, 95 % CI = 0.87-1.28, 4 studies) or oral cavity/pharynx cancer (mRR = 0.68, 95 % CI 0.42-1.11, 3 studies). There were not sufficient studies of any specific neoplasms to perform meta-analysis on the intensity or duration of occupational RF-EMF exposure; individual studies did not show statistically significant associations with either of those exposure metrics and any specific neoplasms. The small number of studies, and of exposed cases in some instances, hampered the assessment of the statistical heterogeneity in findings across studies in the meta-analyses. Based on the summary risk of bias, most studies included in the quantitative evidence syntheses were classified at moderate risk of bias. The most critical issue was exposure information bias, especially for occupational studies where the exposure characterization was rated at high risk of bias for all included studies. Outcome information bias was an issue in mortality-based occupational cohort studies investigating non-rapidly fatal neoplasms. Further, the healthy subscriber effect, and (at a lesser extent) the healthy worker effect, were identified as plausible explanations of the decreased risks observed in some studies. The association of RF-EMF exposure from wireless phone use, or workplace equipment/devices, with other important neoplasms was reported by only one or two studies per tumour, so no quantitative evidence syntheses were conducted on these outcomes. It is noted that there were generally no statistically significant exposure-outcome associations for any combinations, independently of the exposure metric and level, with a few studies reporting decreased risks (especially for smoking-related cancers). There was only one study which assessed the effect of RF-EMF exposure from fixed-site transmitters on less researched neoplasms and it reported no statistically significant associations between exposure from base stations and risk of lymphomas overall, lymphoma subtypes, or chronic lymphatic leukaemia in adults. For near field RF-EMF exposure to the head from mobile phones, there was low certainty of evidence that it does not increase the risk of leukaemia, non-Hodgkin's lymphoma or thyroid cancer. For occupational RF-EMF exposure, there was very low certainty of evidence that it does not increase the risk of lymphohematopoietic system tumours or oral cavity/pharynx cancer. There was not sufficient evidence to assess the effect of whole-body far-field RF-EMF exposure from fixed-site transmitters (broadcasting antennas or base stations), or the effect of RF-EMF from any source on any other important neoplasms. This project was commissioned and partially funded by the World Health Organization (WHO). Co-financing was provided by the New Zealand Ministry of Health; the Istituto Superiore di Sanità in its capacity as a WHO Collaborating Centre for Radiation and Health; and ARPANSA as a WHO Collaborating Centre for Radiation Protection. PROSPERO CRD42021236798. Published protocol: [(Lagorio et al., 2021) DOI https://doi.org/10.1016/j.envint.2021.106828].

Karipidis K ，Baaken D ，Loney T ，Blettner M ，Mate R ，Brzozek C ，Elwood M ，Narh C ，Orsini N ，Röösli M ，Paulo MS ，Lagorio S ... -  《-》

Falls prevention interventions for community-dwelling older adults: systematic review and meta-analysis of benefits, harms, and patient values and preferences.

About 20-30% of older adults (≥ 65 years old) experience one or more falls each year, and falls are associated with substantial burden to the health care system, individuals, and families from resulting injuries, fractures, and reduced functioning and quality of life. Many interventions for preventing falls have been studied, and their effectiveness, factors relevant to their implementation, and patient preferences may determine which interventions to use in primary care. The aim of this set of reviews was to inform recommendations by the Canadian Task Force on Preventive Health Care (task force) on fall prevention interventions. We undertook three systematic reviews to address questions about the following: (i) the benefits and harms of interventions, (ii) how patients weigh the potential outcomes (outcome valuation), and (iii) patient preferences for different types of interventions, and their attributes, shown to offer benefit (intervention preferences). We searched four databases for benefits and harms (MEDLINE, Embase, AgeLine, CENTRAL, to August 25, 2023) and three for outcome valuation and intervention preferences (MEDLINE, PsycINFO, CINAHL, to June 9, 2023). For benefits and harms, we relied heavily on a previous review for studies published until 2016. We also searched trial registries, references of included studies, and recent reviews. Two reviewers independently screened studies. The population of interest was community-dwelling adults ≥ 65 years old. We did not limit eligibility by participant fall history. The task force rated several outcomes, decided on their eligibility, and provided input on the effect thresholds to apply for each outcome (fallers, falls, injurious fallers, fractures, hip fractures, functional status, health-related quality of life, long-term care admissions, adverse effects, serious adverse effects). For benefits and harms, we included a broad range of non-pharmacological interventions relevant to primary care. Although usual care was the main comparator of interest, we included studies comparing interventions head-to-head and conducted a network meta-analysis (NMAs) for each outcome, enabling analysis of interventions lacking direct comparisons to usual care. For benefits and harms, we included randomized controlled trials with a minimum 3-month follow-up and reporting on one of our fall outcomes (fallers, falls, injurious fallers); for the other questions, we preferred quantitative data but considered qualitative findings to fill gaps in evidence. No date limits were applied for benefits and harms, whereas for outcome valuation and intervention preferences we included studies published in 2000 or later. All data were extracted by one trained reviewer and verified for accuracy and completeness. For benefits and harms, we relied on the previous review team's risk-of-bias assessments for benefit outcomes, but otherwise, two reviewers independently assessed the risk of bias (within and across study). For the other questions, one reviewer verified another's assessments. Consensus was used, with adjudication by a lead author when necessary. A coding framework, modified from the ProFANE taxonomy, classified interventions and their attributes (e.g., supervision, delivery format, duration/intensity). For benefit outcomes, we employed random-effects NMA using a frequentist approach and a consistency model. Transitivity and coherence were assessed using meta-regressions and global and local coherence tests, as well as through graphical display and descriptive data on the composition of the nodes with respect to major pre-planned effect modifiers. We assessed heterogeneity using prediction intervals. For intervention-related adverse effects, we pooled proportions except for vitamin D for which we considered data in the control groups and undertook random-effects pairwise meta-analysis using a relative risk (any adverse effects) or risk difference (serious adverse effects). For outcome valuation, we pooled disutilities (representing the impact of a negative event, e.g. fall, on one's usual quality of life, with 0 = no impact and 1 = death and ~ 0.05 indicating important disutility) from the EQ-5D utility measurement using the inverse variance method and a random-effects model and explored heterogeneity. When studies only reported other data, we compared the findings with our main analysis. For intervention preferences, we used a coding schema identifying whether there were strong, clear, no, or variable preferences within, and then across, studies. We assessed the certainty of evidence for each outcome using CINeMA for benefit outcomes and GRADE for all other outcomes. A total of 290 studies were included across the reviews, with two studies included in multiple questions. For benefits and harms, we included 219 trials reporting on 167,864 participants and created 59 interventions (nodes). Transitivity and coherence were assessed as adequate. Across eight NMAs, the number of contributing trials ranged between 19 and 173, and the number of interventions ranged from 19 to 57. Approximately, half of the interventions in each network had at least low certainty for benefit. The fallers outcome had the highest number of interventions with moderate certainty for benefit (18/57). For the non-fall outcomes (fractures, hip fracture, long-term care [LTC] admission, functional status, health-related quality of life), many interventions had very low certainty evidence, often from lack of data. We prioritized findings from 21 interventions where there was moderate certainty for at least some benefit. Fourteen of these had a focus on exercise, the majority being supervised (for > 2 sessions) and of long duration (> 3 months), and with balance/resistance and group Tai Chi interventions generally having the most outcomes with at least low certainty for benefit. None of the interventions having moderate certainty evidence focused on walking. Whole-body vibration or home-hazard assessment (HHA) plus exercise provided to everyone showed moderate certainty for some benefit. No multifactorial intervention alone showed moderate certainty for any benefit. Six interventions only had very-low certainty evidence for the benefit outcomes. Two interventions had moderate certainty of harmful effects for at least one benefit outcome, though the populations across studies were at high risk for falls. Vitamin D and most single-component exercise interventions are probably associated with minimal adverse effects. Some uncertainty exists about possible adverse effects from other interventions. For outcome valuation, we included 44 studies of which 34 reported EQ-5D disutilities. Admission to long-term care had the highest disutility (1.0), but the evidence was rated as low certainty. Both fall-related hip (moderate certainty) and non-hip (low certainty) fracture may result in substantial disutility (0.53 and 0.57) in the first 3 months after injury. Disutility for both hip and non-hip fractures is probably lower 12 months after injury (0.16 and 0.19, with high and moderate certainty, respectively) compared to within the first 3 months. No study measured the disutility of an injurious fall. Fractures are probably more important than either falls (0.09 over 12 months) or functional status (0.12). Functional status may be somewhat more important than falls. For intervention preferences, 29 studies (9 qualitative) reported on 17 comparisons among single-component interventions showing benefit. Exercise interventions focusing on balance and/or resistance training appear to be clearly preferred over Tai Chi and other forms of exercise (e.g., yoga, aerobic). For exercise programs in general, there is probably variability among people in whether they prefer group or individual delivery, though there was high certainty that individual was preferred over group delivery of balance/resistance programs. Balance/resistance exercise may be preferred over education, though the evidence was low certainty. There was low certainty for a slight preference for education over cognitive-behavioral therapy, and group education may be preferred over individual education. To prevent falls among community-dwelling older adults, evidence is most certain for benefit, at least over 1-2 years, from supervised, long-duration balance/resistance and group Tai Chi interventions, whole-body vibration, high-intensity/dose education or cognitive-behavioral therapy, and interventions of comprehensive multifactorial assessment with targeted treatment plus HHA, HHA plus exercise, or education provided to everyone. Adding other interventions to exercise does not appear to substantially increase benefits. Overall, effects appear most applicable to those with elevated fall risk. Choice among effective interventions that are available may best depend on individual patient preferences, though when implementing new balance/resistance programs delivering individual over group sessions when feasible may be most acceptable. Data on more patient-important outcomes including fall-related fractures and adverse effects would be beneficial, as would studies focusing on equity-deserving populations and on programs delivered virtually. Not registered.

Pillay J ，Gaudet LA ，Saba S ，Vandermeer B ，Ashiq AR ，Wingert A ，Hartling L ... -  《Systematic Reviews》