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To simulate possible changes in systematic review results if rapid review methods were used. We recalculated meta-analyses for binary primary outcomes in Cochrane systematic reviews, simulating rapid review methods. We simulated searching only PubMed, excluding older articles (5, 7, 10, 15, and 20 years before the search date), excluding smaller trials (<50, <100, and <200 participants), and using the largest trial only. We examined percentage changes in pooled odds ratios (ORs) (classed as no important change [<5%], small [<20%], moderate [<30%], or large [≥30%]), statistical significance, and biases observed using rapid methods. Two thousand five hundred and twelve systematic reviews (16,088 studies) were included. Rapid methods resulted in the loss of all data in 3.7–44.7% of meta-analyses. Searching only PubMed had the smallest risk of changed ORs (19% [477/2,512] were small changes or greater; 10% [260/2,512] were moderate or greater). Changes in ORs varied substantially with each rapid review method; 8.4–21.3% were small, 1.9–8.8% were moderate, and 4.7–34.1% were large. Changes in statistical significance occurred in 6.5–38.6% of meta-analyses. Changes from significant to nonsignificant were most common (2.1–13.7% meta-analyses). We found no evidence of bias with any rapid review method. Searching PubMed only might be considered where a ∼10% risk of the primary outcome OR changing by >20% could be tolerated. This could be the case in scoping reviews, resource limitation, or where syntheses are needed urgently. Other situations, such as clinical guidelines and regulatory decisions, favor more comprehensive systematic review methods.

Our objectives were, first, to assess the impact of active placebo vs standard placebo control interventions on estimated benefits of experimental interventions in pharmacological randomized clinical trials and to explore causes for heterogeneity and, second, to assess the impact of placebo control type on estimated harm, attrition, and co-intervention use. This was a meta-epidemiological study. We searched PubMed, Ovid Embase, the Cochrane Library, Google Scholar, PROSPERO, citations, and personal files until 2024 and included meta-analyses containing both active placebo-controlled and standard placebo-controlled randomized clinical drug trials from reviews of any topic. We used 2-stage meta-epidemiological models to investigate the impact of placebo control type. The primary analysis was the pooled ratio of odds ratios (RORs) of outcomes of benefit, where ROR < 1 indicated overestimation of benefits in standard placebo-controlled vs active placebo-controlled trials. We investigated robustness in sensitivity analyses and explored heterogeneity. The secondary outcomes were pooled RORs of harm, attrition, and co-intervention use. We included 67 reviews with 123 meta-analyses of 1698 trials. The pooled ROR of benefit was 0.98 (95% CI 0.77–1.24, I2 = 44%, τ2 = 0.30, 95% prediction interval 0.33–2.92, 64 meta-analyses, 727 trials). The result did not change much in sensitivity analyses, and heterogeneity analyses were inconclusive. The results of secondary analyses were imprecise. We did not detect a statistically significant average impact of active placebo vs standard placebo controls on estimated drug effects. However, the results were uncertain as the CIs included important impacts in both directions, and the prediction interval for benefit indicated considerable heterogeneity, which was not reliably explained in the analyses. In many clinical drug trials, patients and health care providers are not told who are allocated to the experimental drug and who are allocated to a similarly looking placebo control. This “blinding” procedure aims to protect against bias by ensuring an impartial assessment. Some patients may, however, experience noticeable side effects from the drug, eg, dry mouth or sedation, which can lead them to guess their allocated intervention. This is called loss of blinding or “unblinding.” Active placebo controls are different from regular placebo controls because they contain ingredients that also imitate the side effects of the drug. We do not know whether this protects against bias from loss of blinding. Therefore, we wanted to assess if trials with active placebo controls yielded different results than similar trials with regular placebo controls. We found such trials by using meta-analyses of comparable trials with both types of placebo controls for various conditions, eg, pain and depression. With more than 100 meta-analyses, including approximately 1700 trials, this is the largest investigation of active placebo controls. We found that in trials using regular placebo controls, the experimental drug effect was slightly larger compared to similar trials with active placebo controls, on average (2%), but there was considerable variation between meta-analyses. The result could be a chance finding and, due to random variation, was compatible with both a 23% exaggeration and 24% underestimation of effect (when measured as odds ratio). In addition, the average may conceal relevant context-specific circumstances under which active placebo controls are more important or less important. We explored several potential circumstances without finding an explanation for the variation between meta-analyses. We conclude that it remains unclear if, and under which circumstances, active placebo controls are more reliable than standard placebo controls. •Uncertain impact of active placebo vs standard placebo controls on drug effects.•The impact may vary in both directions depending on the situation.•For now, trialists could defer to theoretical considerations about choice of placebo control.

Background Consumption of ultra-processed foods (UPFs) plays a potential role in the development of obesity and other diet-related noncommunicable diseases (NCDs), but no studies have systematically focused on this. This study aimed to summarize the evidence for the association between UPFs consumption and health outcomes. Methods A comprehensive search was conducted in PubMed, Embase, and Web of Science to identify all relevant studies. Epidemiological studies were included, and identified studies were evaluated for risk of bias.A narrative review of the synthesized findings was provided to assess the association between UPFs consumption and health outcomes. Results 20 studies (12 cohort and 8 cross-sectional studies) were included in the analysis, with a total of 334,114 participants and 10 health outcomes. In a narrative review, high UPFs consumption was obviously associated with an increased risk of all-cause mortality, overall cardiovascular diseases, coronary heart diseases, cerebrovascular diseases, hypertension, metabolic syndrome, overweight and obesity, depression, irritable bowel syndrome, overall cancer, postmenopausal breast cancer, gestational obesity, adolescent asthma and wheezing, and frailty. It showed no significant association with cardiovascular disease mortality, prostate and colorectal cancers, gestational diabetes mellitus and gestational overweight. Conclusions This study indicated a positive association between UPFs consumption and risk of several health outcomes. Large-scale prospective designed studies are needed to confirm our findings.

Recently, epidemiological studies have suggested that fluoride is a human developmental neurotoxicant that reduces measures of intelligence in children, placing it into the same category as toxic metals (lead, methylmercury, arsenic) and polychlorinated biphenyls. If true, this assessment would be highly relevant considering the widespread fluoridation of drinking water and the worldwide use of fluoride in oral hygiene products such as toothpaste. To gain a deeper understanding of these assertions, we reviewed the levels of human exposure, as well as results from animal experiments, particularly focusing on developmental toxicity, and the molecular mechanisms by which fluoride can cause adverse effects. Moreover, in vitro studies investigating fluoride in neuronal cells and precursor/stem cells were analyzed, and 23 epidemiological studies published since 2012 were considered. The results show that the margin of exposure (MoE) between no observed adverse effect levels (NOAELs) in animal studies and the current adequate intake (AI) of fluoride (50 µg/kg b.w./day) in humans ranges between 50 and 210, depending on the specific animal experiment used as reference. Even for unusually high fluoride exposure levels, an MoE of at least ten was obtained. Furthermore, concentrations of fluoride in human plasma are much lower than fluoride concentrations, causing effects in cell cultures. In contrast, 21 of 23 recent epidemiological studies report an association between high fluoride exposure and reduced intelligence. The discrepancy between experimental and epidemiological evidence may be reconciled with deficiencies inherent in most of these epidemiological studies on a putative association between fluoride and intelligence, especially with respect to adequate consideration of potential confounding factors, e.g., socioeconomic status, residence, breast feeding, low birth weight, maternal intelligence, and exposure to other neurotoxic chemicals. In conclusion, based on the totality of currently available scientific evidence, the present review does not support the presumption that fluoride should be assessed as a human developmental neurotoxicant at the current exposure levels in Europe.

To identify, characterize, and explore author guides on the role, format, and content of protocols for observational epidemiological studies, particularly cohort and case-control studies. Scoping review. We searched for guides in Medline, Embase, Google Scholar, 10 general medical and epidemiological/public health journals, and 10 major funders’ websites. Two review authors extracted data. We classified guides as “main” based on word count and number of protocol items, described such guides more comprehensively and analyzed number of citations as an indicator of uptake. Thirty-nine protocol guides were included intended for cohort studies (n = 3), case-control studies (n = 1), or epidemiological studies in general (n = 35). Content and format were highly variable. Several guides had a broader focus than protocol development, e.g., also including study conduct and reporting. The guideline developmental process was often reported sparsely. One guide, intended for interventional studies, combined a systematic preparatory process with a primary focus on protocol development. We categorized seven guides as ‘main’. In general the guides were cited infrequently, indicating limited uptake. Guides for authors of protocols for observational epidemiological studies varied highly in format and content. We suggest that such guides should routinely be based on a systematic preparatory process. •We identified 39 guides for authors of protocols for observational epidemiological studies.•The content and format of the guides varied considerably, and the developmental process behind the guides was often not reported or sparsely reported.•We suggest that guides for authors of protocols for observational epidemiological studies should routinely be based on a systematic preparatory process.

Phytochemicals are biologically active substances derived from plants that play various roles in the human body [...].Phytochemicals are biologically active substances derived from plants that play various roles in the human body [...].

Rotavirus group A (RVA) is characterized by molecular and epidemiological diversity. To date, 42 G and 58 P RVA genotypes have been identified, some of which, like P[14], have a zoonotic origin. In this study, we describe the epidemiology of unusual RVA genotypes and the molecular characteristics of P[14] strains. Fecal samples from children ≤ 16 years of age with acute gastroenteritis (AGE) who were hospitalized during 2007–2021 in Greece were tested for RVA by immunochromatography. Positive RVA samples were G and P genotyped, and part of the VP7 and VP4 genes were sequenced by the Sanger method. Epidemiological data were also recorded. Phylogenetic analysis of P[14] was performed using MEGA 11 software. Sixty-two (1.4%) out of 4427 children with RVA AGE were infected with an unusual G (G6/G8/G10) or P (P[6]/P[9]/P[10]/P[11]/P[14]) genotype. Their median (IQR) age was 18.7 (37.3) months, and 67.7% (42/62) were males. None of the children were vaccinated against RVA. P[9] (28/62; 45.2%) was the most common unusual genotype, followed by P[14] (12/62; 19.4%). In the last two years, during the period of the COVID-19 pandemic, an emergence of P[14] was observed (5/12, 41.6%) after an 8-year absence. The highest prevalence of P[14] infection was seen in the spring (91.7%). The combinations G8P[14] (41.7%), G6P[14] (41.7%), and G4P[14] (16.6%) were also detected. Phylogenetic analysis showed a potential evolutionary relationship of three human RVA P[14] strains to a fox strain from Croatia. These findings suggest a possible zoonotic origin of P[14] and interspecies transmission between nondomestic animals and humans, which may lead to new RVA genotypes with unknown severity.

Objectives The widespread application of nano-enabled products and the increasing likelihood for workplace exposures make understanding engineered nanomaterial (ENM) effects in exposed workers a public and occupational health priority. The aim of this study was to report on the current state of knowledge on possible adverse effects induced by ENM in humans to determine the toxicological profile of each type of ENM and potential biomarkers for early detection of such effects in workers. Methods A systematic review of human studies and epidemiological investigations of exposed workers relative to the possible adverse effects for the most widely used ENM was performed through searches of major scientific databases including Web of Science, Scopus, and PubMed. Results Twenty-seven studies were identified. Most of the epidemiological investigations were cross-sectional. The review found limited evidence of adverse effects in workers exposed to the most commonly used ENM. However, some biological alterations are suggestive for possible adverse impacts. The primary targets of some ENM exposures were the respiratory and cardiovascular systems. Changes in biomarker levels compared with controls were also observed; however, limited exposure data and the relatively short period since the first exposure may have influenced the incidence of adverse effects found in epidemiological studies. Conclusions There is a need for longitudinal epidemiologic investigations with clear exposure characterizations for various ENM to discover potential adverse health effects and identify possible indicators of early biological alterations. In this state of uncertainty, precautionary controls for each ENM are warranted while further study of potential health effects continues.

Wastewater surveillance locally and globally is important for the investigation of the molecular epidemiological features of SARS-CoV-2 in the environment. The current study investigated the genomic diversity and mutation profile of SARS-CoV-2 variants in wastewater for the period spanning COVID-19 pandemic up to December, 2022. A total of 3618 complete SARS-CoV-2 genome sequences from waste water samples submitted to the GISAID database were retrieved. The SARS-CoV-2 sequences were subjected to pairwise alignment against reference, followed by clade and lineage assignment (based on Nextstrain, GISAID and Pango), distance metric phylogenetic analysis, and detection of substitution mutations. Following GISAID, Nextstrain, and Pango nomenclatures, an overall agreement in clade and lineage determination in wastewater samples was observed. There was successive appearance, dissemination, and disappearance of SARS-CoV-2 lineages along time in wastewater. The SARS-CoV-2 genomes from wastewater were clustered into the variants of concern (VOC) as Alpha GRY (B.1.1.7 + Q.7), Delta GK (B.1.617.2 + AY.*), and Omicron GRA (BA.1*, BA.2* + B.1.1.529, BA.5*). The evolutionary rate was 9.63e-04 substitutions/site/year for SARS-CoV-2 in wastewater. B.1.1.7 was less prevalent than B.1.617.2 in 2021, appeared in succession, and BA.1, BA.2, BA.5 were serially detected in 2022, the latter strain continued to persist in wastewater. The N501Y, E484K/Q, K417N/T, L452R, T478K spike substitutions remained dominant attribute of SARS-CoV-2 VOCs. The study underlines the importance of wastewater surveillance for enumerating spatiotemporal diversity of SARS-CoV-2 variants and mutations, which might pave the way for novel antiviral and vaccine designing towards management and prevention of SARS-CoV-2 infection.

BackgroundThe objectives of this study were to establish the prevalence, risk factors and comorbidities/sequelae for diabetes mellitus (DM) in Australian dogs presented to first-opinion veterinary practices.MethodsElectronic patient records of dogs (n=134,329) attending 152 veterinary clinics during 2017 were sourced through VetCompass Australia. They included 418 dogs with DM; a prevalence of 0.36 per cent (95 per cent CI 0.33 per cent to 0.39 per cent) in Australian dogs attending these veterinary clinics. By comparing with the reference group of rarer breeds and unidentified crossbreeds, multivariable modelling was used to reveal breeds (and their crosses) with significantly higher odds of having DM.ResultsThe results revealed that breeds (and their crosses) with significantly higher odds of having DM were Australian terriers (ORs=7.93 (95 per cent CI 2.83 to 22.27)), Siberian huskies (OR=6.24 (95 per cent CI 2.51 to 15.54)), English springer spaniels (OR=5.37 (95 per cent CI 1.48 to 19.53)), West Highland white terriers (OR=4.85 (95 per cent CI 2.55 to 9.25)), miniature schnauzers (OR=3.47 (95 per cent CI 1.16 to 10.35)), all types of poodles (OR=3.41 (95 per cent CI 2.07 to 5.61)), bichon frises (OR=3.41 (95 per cent CI 1.65 to 7.01)), schnauzers (OR=3.18 (95 per cent CI 1.42 to 7.11)) and cavalier King Charles spaniels (CKCS; OR=1.84 (95 per cent CI 1.08 to 3.13)). Breeds with lower risk were German shepherd dogs (OR=0.11 (95 per cent CI 0.01 to 0.84)), golden retrievers (OR=0.09 (95 per cent CI 0.01 to 0.68)) and boxers (no cases identified). Fisher’s exact tests showed that labradoodles were diagnosed significantly more often than purebred Labradors (P=0.04) and did not differ significantly from poodles (P=0.81). Cavoodles did not differ significantly from either CKCS (p~1.00) or poodles (P=0.12). Spoodles were significantly less diagnosed than poodles (P=0.003) but did not differ from cocker spaniels (P=0.66). Desexed male dogs had a higher odds of DM than entire male (OR=0.62 (95 per cent CI 0.39 to 0.98)) and desexed female dogs (OR=0.76 (95 per cent CI 0.61 to 0.96)). Comorbidities/sequelae associated with canine DM included suspected pancreatitis (OR 10.58 (95 per cent CI 5.17 to 22.78)), cataracts (OR 9.80 (95 per cent CI 5.65 to 17.35)), hyperadrenocorticism (OR 6.21 (95 per cent CI 3.29 to 11.88)), urinary tract infection (OR 5.09 (95 per cent CI 1.97 to 13.41)) and hypothyroidism (OR 4.10 (95 per cent CI 1.08 to 15.58)).ConclusionsBreeds at most risk included Australian terriers and Siberian huskies as previously reported, as well as, for the first time, English springer spaniels. In contrast to other populations where there is female predisposition for DM, desexed male dogs in Australia were at increased risk for DM compared with both entire males and desexed females. This predisposition for desexed males to develop DM warrants further investigation.