Induction of labor vs expectant management among low-risk patients with 1 prior cesarean delivery.

BACKGROUND: Studies that have compared induction of labor in individuals with 1 prior cesarean delivery to expectant management have shown conflicting results. OBJECTIVE: To determine the association between clinical outcomes and induction of labor at 39 weeks in a national sample of otherwise low-risk patients with 1 prior cesarean delivery. STUDY DESIGN: This cross-sectional study analyzed 2016 to 2021 US Vital Statistics birth certificate data. Individuals with vertex, singleton pregnancies, and 1 prior cesarean delivery were included. Patients with prior vaginal deliveries, delivery before 39 weeks 0 days or after 42 weeks 6 days of gestation, and medical comorbidities were excluded. The primary exposure of interest was induction of labor at 39 weeks 0 days to 39 weeks 6 days compared to expectant management with delivery from 40 weeks 0 days to 42 weeks 6 days. The primary outcome was vaginal delivery. The main secondary outcomes were separate maternal and neonatal morbidity composites. The maternal morbidity composite included uterine rupture, operative vaginal delivery, peripartum hysterectomy, intensive care unit admission, and transfusion. The neonatal morbidity composite included neonatal intensive care unit admission, Apgar score less than 5 at 5 minutes, immediate ventilation, prolonged ventilation, and seizure or serious neurological dysfunction. Unadjusted and adjusted log binomial regression models accounting for demographic variables and the exposure of interest (induction vs expectant management) were performed. Results are presented as unadjusted and adjusted risk ratios with 95% confidence intervals. RESULTS: From 2016 to 2021, a total of 198,797 individuals with vertex, singleton pregnancies, and 1 prior cesarean were included in the primary analysis. Of these individuals, 25,915 (13.0%) underwent induction of labor from 39 weeks 0 days to 39 weeks 6 days and 172,882 (87.0%) were expectantly managed with deliveries between 40 weeks 0 days and 42 weeks 6 days. In adjusted analyses, patients induced at 39 weeks were more likely to have a vaginal delivery when compared to those expectantly managed (38.0% vs 31.8%; adjusted risk ratio 1.32, 95% confidence interval 1.28, 1.36). Among those who had vaginal deliveries, induction of labor was associated with increased likelihood of operative vaginal delivery (11.1% vs 10.0; adjusted risk ratio 1.15, 95% confidence interval 1.07, 1.24). The maternal morbidity composite occurred in 0.9% of individuals in both the induction and expectant management groups (adjusted risk ratio 0.92, 95% confidence interval 0.79, 1.06). The rates of uterine rupture (0.3%), peripartum hysterectomy (0.04% vs 0.05%), and intensive care unit admission (0.1% vs 0.2%) were all relatively low and did not differ significantly between groups. There was also no significant difference in the neonatal morbidity composite between the induction and expectant management groups (7.3% vs 6.7%; adjusted risk ratio 1.04, 95% confidence interval 0.98, 1.09). CONCLUSION: When compared to expectant management, elective induction of labor at 39 weeks in low-risk patients with 1 prior cesarean delivery was associated with a significantly higher likelihood of vaginal delivery with no difference in composite maternal and neonatal morbidity outcomes. Prospective studies are needed to better elucidate the risks and benefits of induction of labor in this patient population.

Still to ARRIVE at adequate reporting of orthodontic studies involving animal models.

BACKGROUND: The ARRIVE 2.0 guidelines were introduced to improve the reporting of animal studies. The aim of this study was to assess the reporting adherence of orthodontic speciality animal studies in relation to ARRIVE 2.0 guidelines. Associations between the reporting and study characteristics were explored. MATERIALS AND METHOD: An electronic database search was undertaken using Medline via PubMed (www.pubmed.ncbi.nlm.nih.gov) to identify studies meeting the eligibility criteria published between 1 January 2018 and 31 December 2023. Data extraction was performed in duplicate and independently. Descriptive statistics and frequency distributions for the responses to each checklist item were calculated. Mean values for adequate reporting per ARRIVE item were calculated. A sum score was calculated by adding the responses (0 = not reported, 1 = inadequate reporting, 2 = adequate reporting) per item and sub-questions. On an exploratory basis, univariable linear regression between summary score and study characteristics (year of publication, continent of authorship, type of centre, and number of authors) was performed. RESULTS: Three hundred and eighty-four studies were analysed. Variability in the adequate reporting of the ARRIVE 2.0 guideline items was evident. In particular, in 32% of studies, there was a lack of reporting of the priori sample size calculation. Overall, the mean reporting score for the sample was 57.9 (SD 6.7 and range 34-74). There were no associations between score and study characteristics except for a weak association for year of publication with a small improvement over time (each additional year). CONCLUSIONS: The reporting of animal studies relevant to the speciality of orthodontics is sub-optimal in relation to the ARRIVE 2.0 guidelines. There was a tendency for the non-reporting of items pertaining to study sample size, eligibility, methods to reduce bias and interpretation/scientific implications. Greater awareness and reporting adherence to the ARRIVE 2.0 guidelines are required to reduce research waste involving animal models.

Bedding as a variable affecting fasting blood glucose and vascular physiology in mice.

Rodent husbandry requires careful consideration of environmental factors that may impact colony performance and subsequent physiological studies. Of note, recent reports have suggested corncob bedding may affect a broad range of organ systems. As corncob bedding may contain digestible hemicelluloses, trace sugars, and fiber, we hypothesized that corncob bedding impacts overnight fasting blood glucose and murine vascular function. Here, we compared mice housed on corncob bedding, which were then fasted overnight on either corncob or ALPHA-dri bedding, a virgin paper pulp cellulose alternative. Male and female mice were used from two noninduced, endothelial-specific conditional knockout strains [Cadherin 5-cre/ERT2, floxed hemoglobin-α1 (Hba1fl/fl) or Cadherin 5-cre/ERT2, floxed cytochrome-B5 reductase 3 (CyB5R3fl/fl)] on a C57BL/6J genetic background. After fasting overnight, initial fasting blood glucose was measured, and mice were anesthetized with isoflurane for measurement of blood perfusion via laser speckle contrast analysis using a PeriMed PeriCam PSI NR system. After a 15-min equilibration, the mice were injected intraperitoneally with the α1-adrenergic receptor agonist, phenylephrine (5 mg/kg), or saline, and monitored for changes in blood perfusion. After a 15-min response period, blood glucose was remeasured postprocedure. In both strains, mice fasted on corncob bedding had higher blood glucose than the pulp cellulose group. In the CyB5R3fl/fl strain, mice housed on corncob bedding displayed a significant reduction in phenylephrine-mediated change in perfusion. In the Hba1fl/fl strain, phenylephrine-induced change in perfusion was not different in the corncob group. This work suggests that corncob bedding, in part due to its ingestion by mice, could impact vascular measurements and fasting blood glucose. To promote scientific rigor and improve reproducibility, bedding type should be routinely included in published methods.NEW & NOTEWORTHY This study demonstrates real-time measurement of changes in perfusion to pharmacological treatment using laser speckle contrast analysis. Furthermore, this investigation revealed that fasting mice overnight on corncob bedding has differential effects on vascular function and that there was increased fasting blood glucose in mice fasted on corncob bedding compared with paper pulp cellulose bedding. This highlights the impact that bedding type can have on outcomes in vascular and metabolic research and reinforces the need for thorough and robust reporting of animal husbandry practices.

Cost-effectiveness of induction of labor at 39 weeks vs expectant management by cervical examination.

BACKGROUND: Previous analyses have demonstrated the cost effectiveness of elective induction of labor at 39 weeks of gestation for healthy nulliparous people. However, elective induction of labor is resource intensive, and optimal resource allocation requires a thorough understanding of which subgroups of patients will benefit most. OBJECTIVE: This study aimed to determine whether induction of labor at 39 weeks of gestation is more cost-effective in patients with favorable or unfavorable cervical examinations. STUDY DESIGN: We constructed 2 decision analysis models using TreeAge software: one modeling induction of labor at 39 weeks of gestation vs expectant management for a group of nulliparous patients with unfavorable cervical examinations and the other modeling induction of labor at 39 weeks of gestation vs expectant management for a group with favorable cervical examinations. Estimates of cost, probability, and health state utility were derived from the literature. Based on previous literature, we assumed that people with favorable cervical examinations would have a lower baseline rate of cesarean delivery and higher rates of spontaneous labor. RESULTS: In our base case analysis, induction of labor at 39 weeks of gestation was cost-effective for patients with unfavorable cervical examinations, but not for patients with favorable cervical examinations. The incremental cost per quality-adjusted life year was 50-fold lower for people with unfavorable cervical examinations ($2150 vs $115,100). Induction of labor resulted in 3885 fewer cesarean deliveries and 58 fewer stillbirths per 100,000 patients for those with unfavorable examinations, whereas induction of labor resulted in 2293 fewer cesarean deliveries and 48 fewer stillbirths with labor induction for those with favorable cervical examinations. The results were sensitive to multiple inputs, including the likelihood of cesarean delivery, the cost of induction, the cost of vaginal or cesarean delivery, and the probability of spontaneous labor. In Monte Carlo analysis, the base case findings held true for 64.1% of modeled scenarios for patients with unfavorable cervixes and 55.4% of modeled scenarios for patients with favorable cervixes. CONCLUSION: With a willingness-to-pay threshold of $100,000 per quality-adjusted life year, induction of labor at 39 weeks of gestation may be cost-effective for patients with unfavorable cervical examinations, but not for patients with favorable cervical examinations. This result was driven by the likelihood of labor in patients with favorable cervical examinations, and the resultant avoidance of prolonged pregnancy and its complications, including hypertensive disorders of pregnancy and stillbirths. Health systems may wish to prioritize patients with unfavorable cervical examinations for elective induction of labor at 39 weeks of gestation, which may be opposite to common practice.

Changes in obstetrical practices and pregnancy outcomes following the ARRIVE trial.

BACKGROUND: The ARRIVE trial demonstrated the benefit of induction of labor at 39 weeks gestation. Obstetrics departments across the United States faced the challenge of adapting clinical practice in light of these data while managing logistical constraints. OBJECTIVE: To determine if there were changes in obstetrical practices and perinatal outcomes in the United States after the ARRIVE trial publication. STUDY DESIGN: This was a population-based retrospective cohort study of low-risk, nulliparous women who initiated prenatal care by 12 weeks gestation with singleton, nonanomalous pregnancies delivering at ≥39 weeks. Data were obtained from the US Natality database. The pre-ARRIVE group were women who delivered between January 1, 2015 and December 31, 2017. The post-ARRIVE group consisted of women who delivered between January 1, 2019 and December 31, 2019. Births that occurred in 2018 were excluded. Practice outcomes were rates of induction of labor, timing of delivery, and cesarean delivery rate. Adverse maternal outcomes were blood transfusion and admission to medical intensive care unit. Adverse neonatal outcomes were need for assisted ventilation (immediate and >6 hours), 5-minute APGAR score <3, neonatal intensive care unit admission, seizures, and surfactant use. Univariate and multivariate analyses were performed. Trends were tested across the time period represented by the pre-ARRIVE group using Cochran-Armitage trend test. RESULTS: There were 1,966,870 births in the pre-ARRIVE group and 609,322 in the post-ARRIVE group. The groups differed in age, race, body mass index, marital status, infertility treatment, and smoking history (P<.001). After adjusting for these differences, the post-ARRIVE group was more likely to undergo induction (36.1% vs 30.2%; adjusted odds ratio, 1.36 [1.36-1.37]) and deliver by 39+6 weeks of pregnancy (42.8% vs 39.9%; adjusted odds ratio, 1.14 [1.14-1.15]). The post-ARRIVE group had a significantly lower rate of cesarean delivery than the pre-ARRIVE group (27.3 % vs 27.9%; adjusted odds ratio, 0.94 [0.93-0.94]). Patients in the post-ARRIVE group were more likely to receive a blood transfusion (0.4% vs 0.3%; adjusted odds ratio, 1.43 [1.36-1.50]) and be admitted to medical intensive care unit (0.09% vs 0.08%; adjusted odds ratio, 1.20 [1.09-1.33]). Neonates in the post-ARRIVE group were more likely to need assisted ventilation at birth (3.5% vs 2.8%; adjusted odds ratio, 1.28 [1.26-1.30]) and >6 hours (0.6% vs 0.5%; adjusted odds ratio, 1.36 [1.31-1.41]). The neonates in the post-ARRIVE group were more likely to have low 5-minute APGAR scores (0.4% vs 0.3%; adjusted odds ratio, 0.91 [0.86-0.95]). Neonatal intensive care unit admission did not differ between the 2 groups (4.9% vs 4.9%; adjusted odds ratio, 1.01 [0.99-1.03]). There were no differences in neonatal seizures (0.04% vs 0.04%; adjusted odds ratio, 0.97 [0.84-1.13]), and surfactant use (0.08% vs 0.07%; adjusted odds ratio, 1.05 [0.94-1.17]) between the 2 groups. CONCLUSION: There were more inductions of labor, more deliveries at 39 weeks' gestation, and fewer cesarean deliveries in the year after the ARRIVE trial publication. The small but statistically significant increase in some adverse maternal and neonatal outcomes should be explored to determine if they are related with concurrent changes in obstetrical practices.

Adapting to Changes in Publishing When Searching for Alternatives and Reporting on Animal Research: A Librarian's Perspective.

Since the inaugural issue of ATLA, many changes within publishing have occurred, impacting when, where, and how researchers conduct literature searches for non-animal alternatives. Such changes include increased rate of growth in scientific publications, greater number of databases and online resources available to search, opportunities for open and almost immediate dissemination of research outputs such as preprints and method protocols, and the development of reporting guidelines for animal research. Here we offer a librarian's perspective on these changes and advice on how to manage them to enable robust and diverse alternatives to be implemented in future research.

Randomization, blinding, data handling and sample size estimation in papers published in Veterinary Anaesthesia and Analgesia in 2009 and 2019.

OBJECTIVE: To evaluate reporting of items indicative of bias and weak study design. STUDY DESIGN: Literature survey. POPULATION: Papers published in Veterinary Anaesthesia and Analgesia. METHODS: Reporting of randomization, blinding, sample size estimation and data exclusion were compared for papers published separated by a 10 year interval. A reporting rate of more than 95% was considered ideal. The availability of data supporting results in a publicly accessible repository was also assessed. Selected papers were randomized and identifiers removed for review, with data from 59 (57 in 2009, two in 2008) and 56 (52 in 2019, four in 2018) papers analyzed. Items were categorized for completeness of reporting using a previously published operationalized checklist. Two reviewers reviewed all papers independently. RESULTS: Full reporting of randomization increased over time from 13.6% to 85.7% [95% confidence interval (CI), 57.8-86.6%; p < 0.0001], as did sample size estimation (from 0% to 20%; 95% CI, 7.6-32.4%; p = 0.002). Reporting of blinding (49.2% and 50.0%; 95% CI, -18.3% to 20.0%; p = 1.0) and exclusions of samples/animals (39.0% and 50.0%; 95% CI, -8.8% to 30.8%; p = 0.3) did not change significantly. Data availability was low (2008/2009, zero papers; 2018/2019, two papers). None of the items studied exceeded the predetermined ideal reporting rate. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate that reporting quality remains low, with a risk of bias.

The reporting quality of randomized controlled trials and experimental animal studies for urethroplasty.

OBJECTIVES: To assess the reporting quality of randomized controlled trials and experimental animal studies examining urethroplasty in reconstructive urological surgery literature. METHODS: We performed a comprehensive literature search to identify all urethroplasty-related RCTs examining humans as well as animal models. We used the Consolidated Standards of Reporting Trials (CONSORT) and the Animals in Research: Reporting in vivo Experiments (ARRIVE) guidelines to assess reporting quality. Two reviewers performed data abstraction independently and in duplicate. We then generated descriptive statistics including CONSORT (0-25) and ARRIVE (0-20) summary scores using the median and interquartile range. RESULTS: Twenty studies were ultimately included; 14 randomized controlled trials and 6 experimental animal studies. All studies were two-armed, parallel group studies. Median sample sizes (and interquartile range) of the human and animal studies were 48.5 (31.8-53.8) and 18 (15.3-27.5), respectively. The median CONSORT and ARRIVE scores were 10.0 (8.75-12.63) and 7.97 (6.79-8.64), respectively. Human randomized controlled trials did not consistently report the method of allocation concealment (6/14; 42.9%), blinding (2/14; 14.3%), or discuss the generalizability of the results (6/14; 42.9%). Animal studies infrequently reported why a given animal model was used (1/6; 16.7%), how they were allocated to groups (0/6; 0%) or what the experimental primary and secondary outcomes were (0/6; 0%). CONCLUSIONS: Urethroplasty literature is marked by a paucity of both randomized controlled trials and experimental design animal studies. The existing studies are inconsistently reported and are therefore of uncertain methodological quality.

Reporting in rodent models of 'chemobrain': a systematic review assessing compliance with the ARRIVE guidelines.

Patients diagnosed with cancer are often plagued with debilitating side effects post-chemotherapy treatment. One such side effect is chemotherapy-induced cognitive impairment or 'chemobrain'. Rodent models are commonly used to investigate pathogenesis and potential therapeutic strategies. However, concerns have been raised regarding inadequacies in reporting of animal studies rendering them unreliable and irreproducible. The aim of this systematic review was to assess compliance with the ARRIVE reporting guidelines in peer-reviewed publications evaluating chemotherapy-induced cognitive changes in rodent models, and to determine if the introduction of the ARRIVE guidelines has improved quality of reporting. A comprehensive search was conducted to identify relevant peer-reviewed publications. Ninety-seven studies met the eligibility criteria, and publication compliance with the ARRIVE guideline reporting was assessed. No studies achieved full adherence with the ARRIVE guidelines. Furthermore, no significant improvement was demonstrated in the overall compliance score post-ARRIVE. Given the lack of standardisation of animal models in this research area, these results pose particular threat to future progress and translation of findings in this area of research. These results highlight the need for stricter adherence to the ARRIVE guidelines by journal editors and reviewers. Animal Ethics Committees also have an important educative role in improving knowledge and awareness of the guidelines amongst researchers.

Quality of interventional animal experiments in Chinese journals: compliance with ARRIVE guidelines.

BACKGROUND: In view of the inadequacy and incompleteness of currently-reported animal experiments and their overall poor quality, we retrospectively evaluated the reporting quality of animal experiments published in Chinese journals adhering to the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. RESULTS: The databases CNKI, WanFang, VIP, and CBM were searched from inception until July 2018. Two appropriately-trained reviewers screened and extracted articles independently. The ARRIVE guidelines were used to assess the quality of the published reports of animal experiments. The compliance rate of every item was analyzed relative to their date of publication. A total of 4342 studies were included, of which 73.0% had been cited ≤5 times. Only 29.0% (1261/4342) were published in journals listed in the Chinese Science Citation Database. The results indicate that the compliance rate of approximately half of the sub-items (51.3%, 20/39) was less than 50%, of which 65.0% (13/20) was even less than 10%. CONCLUSIONS: The reporting quality of animal experiments in Chinese journals is not at a high level. Following publication of the ARRIVE guidelines in 2010, the compliance rate of the majority of its requirements has improved to some extent. However, less attention has been paid to the ethics and welfare of experimental animals, and a number of specific items in the Methods, Results, and Discussion sections continue to not be reported in sufficient detail. Therefore, it is necessary to popularize the ARRIVE guidelines, advocate researchers to adhere to them in the future, and in particular promote the use of the guidelines in specialized journals in order that the design, implementation, and reporting of animal experiments is promoted, to ultimately improve their quality.

The Quality of Reporting Raises Questions on the Experimental Validity of Animal Studies Conducted in India and Sri Lanka: Preliminary Analysis of a Systematic Survey.

The quality of animal experiments in terms of appropriate reporting is a concern, particularly with regard to their validity and the recording of the measures taken to reduce various types of bias. A systematic survey of 1371 and 236 publications from India and Sri Lanka, respectively, which were published between 1905 and 2017 and indexed in NCBI-PubMed, Cinhal, MEDLINE and Scopus, was carried out. The level of detail in the descriptions of animals used and the measures taken to reduce bias were analysed in each article. Selected parameters from the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines, such as age, weight, sex, sample size calculation, blinding and randomisation were considered. The findings revealed poor reporting standards in animal experiments carried out in India and Sri Lanka, confirming the limited impact of the ARRIVE guidelines. These findings emphasise the urgent need for improvements in the peer review process, both prior to a study being set up and in the post-study reporting phase, and for more stringent adherence to the ARRIVE guidelines in the reporting of animal experiments.

Ecological fallacy as a novel risk factor for poor translation in neuroscience research: A systematic review and simulation study.

BACKGROUND: Translational neuroscience is largely concerned with establishing causal links between biological processes and functional outcomes. Exciting new methods have emerged and top-tier biomedical journals are placing increasingly high demand for experiments that link outcomes. One pitfall to making these connections is the "ecological fallacy"-establishing a relationship between outcomes based on aggregate (averaged) results (a distinct issue from correlation vs causation). METHODS: To showcase the ecological fallacy, we first used simulated data to define and demonstrate the problem. Next, we performed a systematic review to determine the prevalence of the fallacy in top-tier biomedical journals (Science, Nature Medicine, Neuron, Nature, Nature Neuroscience, Cell). Based on our own research interests and specializations, we specifically focused on recent publications in the area of spinal cord injury and regenerative medicine. RESULTS: Of the articles reviewed which examined a relationship between central nervous system regeneration and a behavioural outcome, 100% (21/21) were subject to possible ecological fallacy. CONCLUSIONS: Ecological fallacy is highly prevalent in neuroscience research and could partially account for translation failures in this field. Reporting guidelines for in vivo experiments should include subject-level correlation analyses for the primary outcomes.

Systematic Review on Characteristics and Reporting Quality of Animal Studies in Liver Regeneration Triggered by Portal Vein Occlusion and Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy: Adherence to the ARRIVE Guidelines.

BACKGROUND: Portal vein occlusion and associating liver partition and portal vein ligation for staged hepatectomy techniques are in the spotlight of oncological liver surgery. Research involving animal models is indispensable to study the mechanisms of liver regeneration. Inaccurate reporting acts as a significant barrier during the correct interpretation of preclinical findings. Hence, we performed a systematic review to evaluate the status quo of the reporting standards and to assess the potential factors influencing reporting in animal studies, which are focusing on portal vein occlusion and/or associating liver partition and portal vein ligation for staged hepatectomy techniques. MATERIALS AND METHODS: A systematic review was performed in the PubMed and Ovid MEDLINE databases. Baseline study characteristics were recorded, and quality assessment was performed using the Animals in Research: Reporting in vivo Experiments (ARRIVE) checklist. RESULTS: A total of 107 research articles were included for the comprehensive assessment. In the subgroup analysis, newer reports and studies from the post-ARRIVE era, and reports from Europe were all associated with significantly higher ARRIVE scores (P < 0.05). Univariable regression analysis confirmed these factors as predictors of higher reporting quality. However, in the multivariable analysis, only publishing in the post-ARRIVE era has been found as single independent predictor of higher reporting standards (P = 0.028 post-ARRIVE total score 75th percentile; P = 0.000 post-ARRIVE total score median). CONCLUSIONS: Although an improving trend has been observed in reporting quality over the past years, this effect was clearly insufficient. Our results emphasize the need for further measures to improve the methodical quality at all levels of planning, execution, and reporting of preclinical studies in liver regeneration research.

Exposure of laboratory animals to small air ions: a systematic review of biological and behavioral studies.

BACKGROUND: Air ions are molecules of air that have become ionized-that is, they have either lost or gained an electrical charge. Past speculation has suggested that exposure to positive air ions may be harmful to one's health, while exposure to negative air ions may be associated with beneficial health effects. Air ions arise from natural sources as well as direct-current transmission lines and commercial ionizers. Several recent clinical studies have suggested therapeutic effects of air ions on various types of depression at exposure levels 10- to 1000-fold higher than most previous human studies. The aim of this study was to assess the evidence from studies of laboratory animals for beneficial or adverse effects of air ions on health. METHODS: Sixty-two studies (1935-2015) in nine topics areas were evaluated for quality and potential systematic bias by ARRIVE guidelines. Standardized mean differences or proportional differences between exposed and control groups were computed for 44 studies to quantitatively assess the strength of the evidence for exposure-related effects. RESULTS: Many of the studies were conducted before 1990 and exhibited various reporting and methodological deficiencies, including small sample size, failure to control for the influence of potential confounding variables, lack of randomized assignment to treatment groups and blinded analyses, and statistical errors relating to treating group-exposed animals as individuals. The highest quality studies consistently reported no effects of exposure on any of the endpoints examined. There were no evident dose-response relationships within or across studies. CONCLUSIONS: Experimental studies of laboratory animals exposed to positive and negative air ions for minutes to years over a five-log unit range of intensities did not suggest any consistent or reliable effects on measures of behavior, learning and memory, neurotransmitters, tracheal function, respiratory infection, cardiovascular function, reproduction and growth, carcinogenesis, or other health endpoints. These data do not provide evidence of adverse or beneficial effects of air ion exposure on health, and did not suggest any biological mechanism of interaction, except perhaps for mechanosensory stimulation of body surfaces by static electric fields at high air ion concentrations.

Bone grafting materials in critical defects in rabbit calvariae. A systematic review and quality evaluation using ARRIVE guidelines.

AIMS: To perform a systematic literature review of the regenerative potential of bone substitutes used to fill critical size defects (CSDs) in rabbit calvariae; to determine the quality of the included studies using ARRIVE guidelines. MATERIAL AND METHODS: An Internet search was performed in duplicate using MEDLINE, PubMed and Google Scholar databases (without restrictions on publication date) for studies reporting the regenerative potential of bone substitutes in CSDs in rabbit calvariae. Four parameters were analyzed by histomorphometry: new bone formation (NB); defect closure (DC); residual graft (RG); and connective tissue (CT). Animal Research Reporting in In Vivo Experiments (ARRIVE) guidelines (a list of 20 aspects for scoring texts and ensuring comparison between different experimental studies in animals) were used to evaluate the quality of the selected works. RESULTS: Twenty-one manuscripts were included. CSDs with 15 mm were predominant (57.14%). Only one study described the four histomorphometric parameters. NB formation was analyzed in 15 studies (71.42%) and was higher for particulate autogenous bone grafts (range 52.1-82%) after 12 weeks. DC was evaluated in six studies (28.57%) and was higher for fragmented adipose tissue grafts (range 53.33-93.33%) after 12 weeks. RG was evaluated in four studies (19.04%) and was higher for hydroxyapatite/beta-tricalcium phosphate grafts with silica (HA/ß-TCP + Si) (range 35.78-47.54%) at 12 weeks. CT was evaluated in two studies (9.5%) and was higher for HA/ß-TCP + membrane (44.2%) at 12 weeks. Quality evaluation identified three items (title, introduction/objectives and experimental procedure) (15%) with excellent scores, 10 items (abstract, introduction/background, methods/ethical statement, experimental animals, experimental outcomes, statistics, results/baseline data, outcome/estimation and discussion interpretation/scientific implications) (50%) with average scores, and seven items (housing and husbandry, sample size, allocation, numbers analyzed, adverse effects, general applicability/relevance and funding) (35%) obtained poor scores. Only one manuscript obtained a quality evaluation considered as excellent. CONCLUSIONS: Autogenous bone grafts increase NB. DC is enhanced by the use of fragmented adipose tissue. RG remains in the defect for longer when hydroxyapatite/beta-tricalcium phosphate with silica is used, and more CT can be expected when hydroxyapatite/beta-tricalcium phosphate with silica grafts are covered by a membrane. The addition of stem cells of different origins to grafting materials enhances bone formation in early healing periods. The ARRIVE guidelines are still insufficiently used and the overall quality of studies remains low.

Recommendations for minimum information for publication of experimental pathology data: MINPEPA guidelines.

Animal models are essential research tools in modern biomedical research, but there are concerns about their lack of reproducibility and the failure of animal data to translate into advances in human medical therapy. A major factor in improving experimental reproducibility is thorough communication of research methodologies. The recently published ARRIVE guidelines outline basic information that should be provided when reporting animal studies. This paper builds on ARRIVE by providing the minimum information needed in reports to allow proper assessment of pathology data gathered from animal tissues. This guidance covers aspects of experimental design, technical procedures, data gathering, analysis, and presentation that are potential sources of variation when creating morphological, immunohistochemical (IHC) or in situ hybridization (ISH) datasets. This reporting framework will maximize the likelihood that pathology data derived from animal experiments can be reproduced by ensuring that sufficient information is available to allow for replication of the methods and facilitate inter-study comparison by identifying potential interpretative confounders.

The future of preclinical animal models in pharmaceutical discovery and development: a need to bring in cerebro to the in vivo discussions.

Animal models have provided an important tool to help make the decision to take potential therapies from preclinical studies to humans. In the past several years, the strong reliance of the pharmaceutical discovery and development process on the use of animal models has come under increasing scrutiny for ethical and scientific reasons. Several prominent and widely publicized articles have reported limited concordance of animal experiments with subsequent human clinical trials. Recent assessments of the quality of animal studies have suggested that this translational failure may be due in part to shortcomings in the planning, conduct, and reporting of in vivo studies. This article will emphasize methods to assure best practice rigor in animal study methods and reporting. It will introduce the so-called scientific 3Rs of relevance, robustness, and reproducibility to the in vivo study approach and will review important new trends in the animal research and pharmaceutical discovery and development communities.