OBJECTIVE: New epidemiologic approaches are needed to reduce the scientific uncertainty surrounding the association between extremely low frequency magnetic fields (ELF-MF) and childhood leukemia. While most previous studies focused on power lines, the Transformer Exposure study sought to assess this association using a multi-country study of children who had lived in buildings with built-in electrical transformers. ELF-MF in apartments above built-in transformers can be 5 times higher than in other apartments in the same building. This novel study design aimed to maximize the inclusion of highly exposed children while minimising the potential for selection bias.
METHODS: We assessed associations between residential proximity to transformers and risk of childhood leukemia using registry based matched case-control data collected in five countries. Exposure was based on the location of the subject\'s apartment relative to the transformer, coded as high (above or adjacent to transformer), intermediate (same floor as apartments in high category), or unexposed (other apartments). Relative risk (RR) for childhood leukemia was estimated using conditional logistic and mixed logistic regression with a random effect for case-control set.
RESULTS: Data pooling across countries yielded 16 intermediate and 3 highly exposed cases. RRs were 1.0 (95% CI: 0.5, 1.9) for intermediate and 1.1 (95% CI: 0.3, 3.8) for high exposure in the conditional logistic model. In the mixed logistic model, RRs were 1.4 (95% CI: 0.8, 2.5) for intermediate and 1.3 (95% CI: 0.4, 4.4) for high. Data of the most influential country showed RRs of 1.1 (95% CI: 0.5, 2.4) and 1.7 (95% CI: 0.4, 7.2) for intermediate (8 cases) and high (2 cases) exposure.
CONCLUSIONS: Overall, evidence for an elevated risk was weak. However, small numbers and wide confidence intervals preclude strong conclusions and a risk of the magnitude observed in power line studies cannot be excluded.

UNASSIGNED: Brucellosis may affect the eye to varying degrees. The aim of this study was to investigate the ocular involvement of brucellosis and highlight key points.
UNASSIGNED: Published literature in English language on the ocular involvement of brucellosis within last 30 years was evaluated. The PubMed international database was screened using certain keywords.
UNASSIGNED: The study included 27 publications evaluating a total of 159 cases. The most common types of ocular involvement were uveitis (52.2%) and conjunctivitis (17.6%). Most cases had concomitant systemic brucellosis (27.7%), and the most commonly used diagnostic method was a serological test (92.4%). Of all the patients, 37.1% recovered with sequelae.
UNASSIGNED: Brucellosis may cause a wide range of ophthalmic manifestations, and an overlooked or late diagnosis may also lead to the development of sequelae or loss of vision. A routine ophthalmologic examination should be performed in all patients with systemic brucellosis.

UNASSIGNED: Metabolic changes may occur following gastric surgery, which has been reported to contribute to bone loss, osteoporosis and even bone fracture. However, the evidence regarding the relationship between gastric surgery for benign and malignant conditions and risk of fracture is controversial. This study was conducted with the aim to evaluate whether gastric surgery is associated with a high risk of fracture.
UNASSIGNED: Major electronic databases were searched from inception through October 2021 for population-based cohort studies investigating the associations between gastric surgery (including bariatric gastric surgeries and surgeries for gastric benign and malignant gastric tumors) and risk of fracture compared with controls. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were derived using the random-effects Mantel-Haenszel model. Multiple subgroup analyses and sensitivity analyses were carried out to test sources of heterogeneity stratified by various study characteristics and the robustness of the results.
UNASSIGNED: A total of 14 studies comprising 693134 individuals were identified for analysis. The RR for the risk of fracture in people undergoing gastric surgery was 1.45 [95% confidence interval (CI) 1.23 - 1.72; I2 = 95.8%; P < 0.001] compared with that in control populations, among which the fracture sites of upper limb, spine, lower limb, pelvis and hip showed consistent significant results (all P < 0.05), whereas nonsignificant associations was noted for other fracture sites. Significant associations were also observed for patients having total or subtotal gastrectomy (RR 2.22, 95% CI 1.66 to 3.00), gastric bypass (RR 1.48, 95% CI 1.26 to 1.74), and a similar trend was observed for preserved passage procedures (including sleeve gastrectomy, gastric banding, vertical banded gastroplasty and other procedures that preserved the passage through the duodenum and proximal small bowel, in contrast to gastric bypass), though the difference did not reach statistically significant (RR 1.10, 95% CI 0.95 to 1.26). An evident increased risk in the age range from 40-59 years was observed (40-49 years: RR 1.36, 95% CI 1.19-1.55; 50-59 years: RR 2.48, 95% CI 1.58-3.90).
UNASSIGNED: From this large pooled analysis of population-based cohort studies, evidence supports that fracture risk is increased in gastric surgery survivors compared with the control population. Early prevention and effective intervention strategies of bone fracture should be taken from clinicians and health policy makers.
UNASSIGNED: PROSPERO (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=291394), identifier CRD42021291394.

Background: Accumulating evidence suggests that traditional Chinese medicine (TCM) has significant effects on reducing 24-h urinary protein (24-h UPRO) and improves renal function indices. The current level of evidence-based medicine is still not enough due to the limitation of clinical center size and sample size. Objective: We aimed to update the current evidence on the efficacy of TCM in the treatment of diabetic kidney disease (DKD). Methods: PubMed, Embase, the Cochrane Library, and SinoMed were searched to identify randomized controlled trials (RCTs) comparing the clinical efficacy of TCM combined with Western medicine with that of Western medicine alone for the treatment of DKD. The main outcome measure was 24-h UPRO. The secondary outcomes were serum creatinine (Scr), blood urea nitrogen (BUN), glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), total cholesterol (TC), and triglyceride (TG). Meta-analyses were performed using random-effects models. The revised Cochrane risk-of-bias tool was used to assess the risk of bias. Results: A total of 44 RCTs with 3,730 participants were included. The summary estimates showed that compared with Western medicine alone, TCM combined with Western medicine significantly improved 24-h UPRO [standardized mean difference (SMD) -1.10, 95% confidence interval (CI) -1.45 to -0.74]. Moreover, TCM combined with Western medicine significantly reduced the levels of other renal function indices, including Scr (SMD -1.25, 95% CI: -1.69 to -0.81) and BUN (SMD -0.75, 95% CI: -1.10 to -0.40). TCM combined with Western medicine also showed greater benefits in reducing the levels of FBG (SMD -0.31, 95% CI: -0.47 to -0.15) and HbA1c (SMD -0.62, 95% CI: -0.89 to -0.36) in patients with DKD. In addition, superior effects on the lipid profile were noted in the TCM combined with Western medicine group in terms of TG (SMD -1.17, 95% CI: -1.76 to -0.59) and TC (SMD -0.95, 95% CI: -1.43 to -0.47). The risk of bias could have resulted from selective reports, unclear randomization methods, unblinded assignments, and some missing data. Conclusion: The results of this meta-analysis suggest that TCM combined with Western medicine has significant effects on reducing 24-h UPRO and improves renal function indices and lipid profiles compared with Western medicine alone for DKD. However, the results should be interpreted with caution due to the risk of bias of the included trials. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=213199], identifier [CRD: 42020213199].

Two significant pivotal trials are usually required for a new drug approval by a regulatory agency. This standard requirement is known as the two-trial paradigm. However, several authors have questioned why we need exactly two pivotal trials, what statistical error the regulators are trying to protect against, and potential alternative approaches. Therefore, it is important to investigate these questions to better understand the regulatory decision-making in the assessment of drugs\' effectiveness. It is common that two identically designed trials are run solely to adhere to the two-trial rule. Previous work showed that combining the data from the two trials into a single trial (one-trial paradigm) would increase the power while ensuring the same level of type I error protection as the two-trial paradigm. However, this is true only under a specific scenario and there is little investigation on the type I error protection over the whole null region. In this article, we compare the two paradigms by considering scenarios in which the two trials are conducted in identical or different populations as well as with equal or unequal size. With identical populations, the results show that a single trial provides better type I error protection and higher power. Conversely, with different populations, although the one-trial rule is more powerful in some cases, it does not always protect against the type I error. Hence, there is the need for appropriate flexibility around the two-trial paradigm and the appropriate approach should be chosen based on the questions we are interested in.

OnabotulinumtoxinA, targeting the CGRP machinery, has been approved for the last two decades for chronic migraine prevention. The recently approved monoclonal antibodies (mAbs) directed towards the calcitonin gene-related peptide (CGRP) pathway open a new age for chronic migraine control. However, some 40% patients suffering from chronic migraine is still resistant to treatment. The aim of this work is to answer the following PICOS (participants intervention comparator outcome study design) question: Is there evidence of efficacy and safety of the combined administration of anti-CGRP mAbs and onabotulinumtoxinA in chronic migraine? A systematic review and meta-analysis [Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations] was made up to 19 April 2022. The results are encouraging: the combined treatment proved to afford ≥50% monthly headache days (MHDs)/frequency reduction respect to baseline in up to 58.8% of patients; in comparison, anti-CGRP mAbs reduce MHDs of 1.94 days from baseline and botulinum toxin of 1.86 days. Our study demonstrates for the first time that the combination therapy of onabotulinumtoxinA with anti-CGRP mAbs affords a reduction of 2.67 MHDs with respect to onabotulinumtoxinA alone, with moderate certainty of evidence. Adequately powered, good-quality studies are needed to confirm the response to combination therapy in terms of efficacy and safety. PROSPERO registration: CRD42022313640.

BACKGROUND: Optimization of COVID-19 vaccination rate among healthcare personnel is of utmost priority to secure provision of uninterrupted care and to protect the most vulnerable patients. This study, as part of the global CoVaST project, aimed to assess the occurrence of short-term adverse events (SRAEs) of two most administered COVID-19 vaccines, mRNA-based (Pfizer-BioNTech and Moderna) and viral vector-based (AstraZeneca) in healthcare sector workers (HWs).
METHODS: A cross-sectional survey-based study was carried out for the first time among 317 Polish healthcare sector personnel and medical students using a validated and pre-tested questionnaire. The online questionnaire included 25 pre-tested, validated questions concerning demographic data, medical parameters, COVID-19-related anamneses, and local or systemic reactions (reactogenicity) associated with COVID-19 vaccination. Descriptive statistics, inferential tests and binary logistic regression were performed.
RESULTS: Out of the 247 participating HWs, 79.8% were females, and 77.5% received mRNA-based vaccines, while 24.5% received a viral vector-based vaccine. Cumulatively, 78.9% and 60.7% of the participants reported at least one local and one systemic SRAE respectively, following their COVID-19 first or second dose of vaccine. A wide array of SRAEs was observed, while pain at injection site (76.9%) was the most common local SRAE, and fatigue (46.2%), headache (37.7%), muscle pain (31.6%) were the most common systemic SRAEs. The vast proportion of local (35.2%) and systemic (44.8%) SRAEs subsided up to 1 day after inoculation with both types of vaccines. The mRNA-based vaccine versions seem to cause higher prevalence of local SRAEs, mainly pain within injection site (81.3% vs. 71.7%; p = 0.435), while the viral vector-based vaccine was linked with increased incidents of mild systemic side effects (76.7% vs. 55.3%; p = 0.004) after both doses. Pooled analysis revealed uniform results while comparing the prevalence of SRAEs in HWs as recipients in four central European countries (OR = 2.38; 95% CI = 2.03-2.79).
CONCLUSIONS: The study confirmed the safety of commonly administered vaccines against COVID-19, which were associated with mild, self-resolving adverse events. No major vaccine-related incidents were reported which would affect every day functioning, significantly. The younger age group (below 29 y.o.) were associated with an increased risk of adverse events generally. The results enhanced current data regarding COVID-19 vaccination active surveillance in selected occupational groups.

OBJECTIVE: To investigate nurses\' intention in accepting COVID-19 vaccination and the factors affecting their decision.
BACKGROUND: COVID-19 vaccination has started in most European countries with healthcare personnel being the first group receiving the vaccine shots. Their attitude towards vaccination is of paramount significant as their role in the frontline could help in the awareness of general population.
METHODS: A study was conducted in Albania, Cyprus, Greece, Spain and Kosovo with the use of an online questionnaire. The Fear of COVID-19 Scale was used. The STROBE checklist was followed for this cross-sectional study.
RESULTS: Study population consisted of 1135 nurses. Mean age of the participants was 38.3 years, while most of them were female gender (84.7%) and married (53.1%). Acceptance of a safe and effective COVID-19 vaccine was higher among Greek (79.2%) and Spanish (71.6%) nurses, followed by Cypriot (54%), Albanian (46.3%) and Kosovo (46.2%) nurses. Key factors for willingness to get vaccinated were male gender, living in a country with a high mortality rate in comparison with low mortality, being not infected with COVID-19, having high level of knowledge about COVID-19 vaccines and having been vaccinated for influenza in the last 2 years. Moreover, trusting the government and doctors regarding the information about the COVID-19 and having high level of fear about this virus were key factors for willingness to get vaccinated.
CONCLUSIONS: Vaccination of healthcare personnel is a crucial issue not only for their own safety but also for their patients\'. Healthcare acceptance to get vaccinated can work as a role model for general population.
CONCLUSIONS: Gender, country, mortality rate, trust in government and health professionals and the level of fear were key factors that should be managed in clinical practice.

Diabetes mellitus (DM) is a systemic disease characterized by chronic hyperglycemia associated with inflammation and oxidative stress, and the lung may be a target organ of diabetic microvascular damage. Several studies have indicated a positive association between idiopathic pulmonary fibrosis (IPF) and diabetes with controversial findings.
Primary outcomes were to compare the prevalence of DM among individuals with IPF to non-IPF controls, and the prevalence of IPF among individuals with DM to non-DM controls.
Data sources include PubMed, EMBASE, and the Cochrane Library. Studies contained sufficient data to calculate the prevalence of DM among individuals with and without IPF, or the prevalence of IPF among individuals with and without DM. Two investigators independently identified eligible studies and extracted data. Pooled odds ratio (OR) with 95% CI was the summary effect measure.
Eighteen studies including 26 410 623 individuals met the eligibility criteria, of whom 16 recruited people with IPF and 2 recruited people with DM. The OR of DM in IPF patients was 1.54 (95% CI, 1.30-1.84; P < .001) compared to that in non-IPF controls. However, compared with that in non-DM patients, the risk of IPF in DM patients was not found to be significantly reduced (OR: 0.89; 95% CI, 0.64-1.25; P = .497).
This meta-analysis suggests that people with IPF have 1.54 times increased odds of diabetes compared to non-IPF controls, while whether patients with DM have an increased risk of IPF is still controversial. Further large, prospective cohort studies investigating the prevalence of IPF in diabetic patients are warranted.

This analysis of pooled individual patient data (IPD) aimed to evaluate the safety and efficacy of a bioresorbable polymer sirolimus eluting stent system (BP-SES; Orsiro) compared to a durable polymer everolimus eluting stent system (DP-EES; Xience) in the pooled population as well as in subgroups.
IPD with up to 12 months follow-up of the randomized controlled trials BIOFLOW-II (NCT01356888), -IV (NCT01939249), and -V (NCT02389946) as well as the all comers registry BIOFLOW-III (NCT01553526) were pooled. A total of 3,717 subjects (2,923 in BP-SES and 794 in DP-EES) with 5,328 lesions (4,225 lesions in BP-SES and 1,103 in DP-EES) were included in the IPD. The primary endpoint was target lesion failure (TLF) at 12 months follow-up. Subgroups analyzed included diabetes, age (≥65 years), gender, complex lesions (B2/C), small vessels (reference vessel diameter ≤2.75 mm), multivessel treatment, renal disease, and patients with acute coronary syndrome.
Overall, TLF at 12 months was significantly lower with 5.2%in the BP-SES group versus 7.6% in the DP-EES group (p = .0098). Similarly, target vessel myocardial infarction (TV-MI) was 3.1 versus 5.7% (p = .0005). The rate of stent thrombosis was similar in both groups (0.004%). By regression analysis, an independent stent effect in favor of BP-SES was observed for TLF (p = .0043) and TV-MI (p = .0364) in small vessels.
Results of this IPD analysis suggest that the BP-SES with ultrathin struts is as safe as and more efficacious than DP-EES in the overall cohort and especially in small vessels.