The randomized clinical trial trustworthiness crisis

Background The rising number of retracted randomised clinical trials (RCTs) is a concern over their trustworthiness. In today’s digital landscape electronic observational data is easily accessible for research purposes. This emerging perspective, in tandem with the growing scrutiny of RCT credibility, may steer some researchers towards favouring non-randomized studies. It is crucial to emphasize the ongoing need for robust RCTs, shedding light on the areas within trial design that require enhancements and addressing existing gaps in trial execution. Main body Evidence-based medicine pivots on the nexus between empirical medical research and the theoretical and applied facets of clinical care. Healthcare systems regularly amass patient data, creating a vast reservoir of information. This facilitates large-scale observational studies, which may appear as potential substitutes for RCTs. These large-scale studies inherently possess biases that place them a notch below randomized evidence. Honest errors, data manipulation, lapses in professionalism, and methodological shortcomings tarnish the integrity of RCTs, compromising trust in trials. Research institutions, funding agencies, journal editors and other stakeholders have the responsibility to establish robust frameworks to prevent both deliberate and inadvertent mishandling of RCT design, conduct and analysis. Systematic reviews that collate robust RCTs are invaluable. They amalgamate superior evidence instrumental in improving patient outcomes via informed health policy decisions. For systematic reviews to continue to retain trust, validated integrity assessment tools must be developed and routinely applied. This way it will be possible to prevent false or untrustworthy research from becoming part of the recommendations based on the evidence. Conclusion High-quality RCTs and their systematic reviews play a crucial role in acquiring valid and reliable evidence that is instrumental in improving patient outcomes. They provide vital information on healthcare effectiveness, and their trustworthiness is key to evidence-based medicine.Beatriz Galindo (senior modality) programme of the Spanish Ministry of Educatio

The reproductive potential of vitrifiedwarmed euploid embryos declines following repeated uterine transfers

Background Recurrent implantation failure (RIF) represents a vague clinical condition with an unclear diagnostic challenge that lacks solid scientific underpinning. Although euploid embryos have demonstrated consistent implantation capabilities across various age groups, a unanimous agreement regarding the advantages of preimplantation genetic testing for aneuploidy (PGT-A) in managing RIF is absent. The ongoing discussion about whether chromosomal aneuploidy in embryos significantly contributes to recurrent implantation failure remains unsettled. Despite active discussions in recent times, a universally accepted characterization of recurrent implantation failure remains elusive. We aimed in this study to measure the reproductive performance of vitrified-warmed euploid embryos transferred to the uterus in successive cycles. Methods This observational cohort study included women (n = 387) with an anatomically normal uterus who underwent oocyte retrieval for PGT-A treatment with at least one biopsied blastocyst, between January 2017 and December 2021 at a university-affiliated public fertility center. The procedures involved in this study included ICSI, blastocyst culture, trophectoderm biopsy and comprehensive 24-chromosome analysis of preimplantation embryos using Next Generation Sequencing (NGS). Women, who failed a vitrified-warmed euploid embryo transfer, had successive blastocyst transfer cycles (FET) for a total of three using remaining cryopreserved euploid blastocysts from the same oocyte retrieval cycle. The primary endpoints were sustained implantation rate (SIR) and live birth rate (LBR) per vitrified-warmed single euploid embryo. The secondary endpoints were mean euploidy rate (m-ER) per cohort of biopsied blastocysts from each patient, as well as pregnancy and miscarriage rates. Results The mean age of the patient population was 33.4 years (95% CI 32.8–33.9). A total of 1,641 embryos derived from the first oocyte retrieval cycle were biopsied and screened. We found no associations between the m-ER and the number of previous failed IVF cycles among different ranges of maternal age at oocyte retrieval (P = 0.45). Pairwise comparisons showed a significant decrease in the sustained implantation rate (44.7% vs. 30%; P = 0.01) and the livebirth rate per single euploid blastocyst (37.1% vs. 25%; P = 0.02) between the 1st and 3rd FET. The cumulative SIR and LBR after up to three successive single embryo transfers were 77.1% and 68.8%, respectively. We found that the live birth rate of the first vitrified-warmed euploid blastocyst transferred decreased significantly with the increasing number of previously failed IVF attempts by categories (45.3% vs. 35.8% vs. 27.6%; P = 0.04). A comparable decrease in sustained implantation rate was also observed but did not reach statistical significance (50% vs. 44.2 vs. 37.9%; P = NS). Using a logistic regression model, we confirmed the presence of a negative association between the number of previous IVF failed attempts and the live birth rate per embryo transfer cycle (OR = 0.76; 95% CI 0.62–0.94; P = 0.01). Conclusions These findings are vital for enhancing patient counseling and refining management strategies for individuals facing recurrent implantation failure. By tailoring interventions based on age and ovarian reserve, healthcare professionals can offer more personalized guidance, potentially improving the overall success rates and patient experiences in fertility treatments

Hospitalisation by tick-borne diseases in the last 10 years in two hospitals in South Spain: analysis of tick exposure data collected in the Emergency Department

Tick-borne diseases (TBDs) can sometimes cause severe symptoms and lead to hospitalisation, but they often go unnoticed in the Emergency Department (ED). The aim of this study was twofold: (i) to describe the profile of patients hospitalised by TBDs; and (ii) to evaluate the data collected in the medical records from the ED in order to analyse their potential clinical consequences. A total of 84 cases that included all TBD diagnoses registered in the ED records were identified and analysed. These corresponded to all the hospitalisations by TBDs in the last 10 years (2009–2019) in two tertiary hospitals in Granada, Spain. Statistical analyses were made using RStudio. Coinciding with the absence of patient’s report of exposure to ticks, 64.3% of TBDs were not suspected in the ED. Intensive care unit admission was required in 8.3% of cases, and the mortality rate was 2.4%. Non-suspected cases showed longer hospital stay (P < 0.001), treatment duration (P = 0.02) and delay in the initiation of antibiotic treatment (P < 0.001). Our findings indicate that symptoms associated with TBDs are highly non-specific. In the absence of explicit information related to potential tick exposure, TBDs are not initially suspected. As a consequence, elective treatment administration is delayed and hospitalisation time is prolonged. In conclusion, our results highlight the importance of addressing potential exposure to ticks during the ED contact with patients presenting with febrile syndrome

The association between timed up and go test and history of falls: The Tromsø study

BACKGROUND: Fall-related injuries in older adults are a major health problem. Although the aetiology of falls is multifactorial, physical factors are assumed to contribute significantly. The "Timed up and go test" (TUG) is designed to measure basic mobility function. This report evaluates the association between TUG times and history of falls. METHODS: A retrospective, observational, population-based study was conducted on 414 men and 560 women with mean age 77.5 (SD 2.3). TUG time and falls during the previous 12 months were recorded. Covariates were age, sex, medical history and health-related mobility problems. Means, confidence intervals and test characteristics for TUG were calculated. Odds ratios and influence of covariates were examined by logistic regression. RESULTS: The mean TUG time was 11.1s (SD 2.5) among male non-fallers and 13.0s (SD 7.8) among fallers. The difference was 1.9s (95%CI 0.9–3.0). The odds ratio for fallers being in the upper quartile was 2.1 (95%CI 1.4–3.3). Adjusted for covariates, the odds ratio was (OR = 1.8, 95%CI 1.1–2.9). The corresponding mean was 13.0s (SD 5.74) among female non-fallers and 13.9s (SD 8.5) among fallers. The difference was 0.9 (95%CI -0.3–2.1). The odds ratio for fallers being in upper quartile was 1.0 (95%CI 0.7–1.4). The area under the ROC curve was 0.50 (95%CI 0.45–0.55) in women and 0.56 (95%CI 0.50–0.62) in men. CONCLUSION: TUG is statistically associated with a history of falls in men but not in women. The ability to classify fallers is poor, and the clinical value of the association is therefore limited

Clinical factors associated with a conservative gait pattern in older male veterans with diabetes

<p>Abstract</p> <p>Background</p> <p>Patients with diabetes and peripheral neuropathy are at higher risk for falls. People with diabetes sometimes adopt a more conservative gait pattern with decreased walking speed, widened base, and increased double support time. The purpose of this study was to use a multivariate approach to describe this conservative gait pattern.</p> <p>Methods</p> <p>Male veterans (mean age = 67 years; SD = 9.8; range 37–86) with diabetes (n = 152) participated in this study from July 2000 to May 2001 at the Veterans Affairs Medical Center, White River Junction, VT. Various demographic, clinical, static mobility, and plantar pressure measures were collected. Conservative gait pattern was defined by visual gait analysis as failure to demonstrate a heel-to-toe gait during the propulsive phase of gait.</p> <p>Results</p> <p>Patients with the conservative gait pattern had lower walking speed and decreased stride length compared to normal gait. (0.68 m/s v. 0.91 m/s, <it>p </it>< 0.001; 1.04 m v. 1.24 m, <it>p </it>< 0.001) Age, monofilament insensitivity, and Romberg's sign were significantly higher; and ankle dorsiflexion was significantly lower in the conservative gait pattern group. In the multivariate analysis, walking speed, age, ankle dorsiflexion, and callus were retained in the final model describing 36% of the variance. With the inclusion of ankle dorsiflexion in the model, monofilament insensitivity was no longer an independent predictor.</p> <p>Conclusion</p> <p>Our multivariate investigation of conservative gait in diabetes patients suggests that walking speed, advanced age, limited ankle dorsiflexion, and callus describe this condition more so than clinical measures of neuropathy.</p

Shared decision making in breast cancer treatment guidelines: Development of a quality assessment tool and a systematic review

Background: It is not clear whether clinical practice guidelines (CPGs) and consensus statements (CSs) are adequately promoting shared decision making (SDM). Objective: To evaluate the recommendations about SDM in CPGs and CSs concerning breast cancer (BC) treatment. Search strategy: Following protocol registration (Prospero no.: CRD42018106643), CPGs and CSs on BC treatment were identified, without language restrictions, through systematic search of bibliographic databases (MEDLINE, EMBASE, Web of Science, Scopus, CDSR) and online sources (12 guideline databases and 51 professional society websites) from January 2010 to December 2019. Inclusion criteria: CPGs and CSs on BC treatment were selected whether published in a journal or in an online document. Data extraction and synthesis: A 31-item SDM quality assessment tool was developed and used to extract data in duplicate. Main results: There were 167 relevant CPGs (139) and CSs (28); SDM was reported in only 40% of the studies. SDM was reported more often in recent publications after 2015 (42/101 (41.6 %) vs 46/66 (69.7 %), P = .0003) but less often in medical journal publications (44/101 (43.5 %) vs 17/66 (25.7 %), P = .009). In CPGs and CSs with SDM, only 8/66 (12%) met one-fifth (6 of 31) of the quality items; only 14/66 (8%) provided clear and precise SDM recommendations. Discussion and conclusions: SDM descriptions and recommendations in CPGs and CSs concerning BC treatment need improvement. SDM was more frequently reported in CPGs and CSs in recent years, but surprisingly it was less often covered in medical journals, a feature that needs attention

Water intake, hydration status and 2-year changes in cognitive performance: a prospective cohort study

BackgroundWater intake and hydration status have been suggested to impact cognition; however, longitudinal evidence is limited and often inconsistent. This study aimed to longitudinally assess the association between hydration status and water intake based on current recommendations, with changes in cognition in an older Spanish population at high cardiovascular disease risk.MethodsA prospective analysis was conducted of a cohort of 1957 adults (aged 55-75) with overweight/obesity (BMI between >= 27 and = 300 mmol/L (dehydrated). Water intake was assessed as total drinking water intake and total water intake from food and beverages and according to EFSA recommendations. Global cognitive function was determined as a composite z-score summarizing individual participant results from all neuropsychological tests. Multivariable linear regression models were fitted to assess the associations between baseline hydration status and fluid intake, continuously and categorically, with 2-year changes in cognitive performance.ResultsThe mean baseline daily total water intake was 2871 +/- 676 mL/day (2889 +/- 677 mL/day in men; 2854 +/- 674 mL/day in women), and 80.2% of participants met the ESFA reference values for an adequate intake. Serum osmolarity (mean 298 +/- 24 mmol/L, range 263 to 347 mmol/L) indicated that 56% of participants were physiologically dehydrated. Lower physiological hydration status (i.e., greater serum osmolarity) was associated with a greater decline in global cognitive function z-score over a 2-year period (beta: - 0.010; 95% CI - 0.017 to - 0.004, p-value = 0.002). No significant associations were observed between water intake from beverages and/or foods with 2-year changes in global cognitive function.ConclusionsReduced physiological hydration status was associated with greater reductions in global cognitive function over a 2-year period in older adults with metabolic syndrome and overweight or obesity. Future research assessing the impact of hydration on cognitive performance over a longer duration is needed

The development of a multidisciplinary fall risk evaluation tool for demented nursing home patients in the Netherlands

BACKGROUND: Demented nursing home patients are at high risk for falls. Falls and associated injuries can have a considerable influence on the autonomy and quality of life of patients. The prevention of falls among demented patients is therefore an important issue. In order to intervene in an efficient way in this group of patients, it is important to systematically evaluate the fall risk profile of each individual patient so that for each patient tailor-made preventive measures can be taken. Therefore, the objective of the present study is to develop a feasible and evidence based multidisciplinary fall risk evaluation tool to be used for tailoring preventive interventions to the needs of individual demented patients. METHODS: To develop this multidisciplinary fall risk evaluation tool we have chosen to combine scientific evidence on the one hand and experts' opinions on the other hand. Firstly, relevant risk factors for falling in elderly persons were gathered from the literature. Secondly, a group of Dutch experts in the field of falls and fall prevention in the elderly were consulted to judge the suitability of these risk factors for use in a multidisciplinary fall risk evaluation tool for demented nursing home patients. Thirdly, in order to generate a compact list of the most relevant risk factors for falling in demented elderly, all risk factors had to fulfill a set of criteria indicating their relevance for this specific target population. Lastly the final list of risk factors resulting from the above mentioned procedure was presented to the expert group. The members were also asked to give their opinion about the practical use of the tool. RESULTS: The multidisciplinary fall risk evaluation tool we developed includes the following items: previous falls, use of medication, locomotor functions, and (correct) choice and use of assistive and protective devices. The tool is developed for the multidisciplinary teams of the nursing homes. CONCLUSION: This evidence and practice based multidisciplinary fall risk evaluation tool targets the preventive interventions aimed to prevent falls and their negative consequences in demented nursing home patients

Validity of the energy-restricted Mediterranean Diet Adherence Screener

[Background]: Short dietary assessment tools can be useful to estimate food intake and diet quality in large-scale epidemiological studies with time constraints. [Objective]: To determine the concurrent validity of the 17-item energy-restricted Mediterranean Adherence Screener (er-MEDAS) used in the PREDIMED (PREvención con DIeta MEDiterránea)-Plus trial and to analyse its capacity to detect 1-year changes in diet and cardiometabolic risk factors. [Methods]: Validation study nested in the PREDIMED-Plus (n = 6760, 55–75 years). Dietary data were collected by the 17-item er-MEDAS and a 143-item validated semiquantitative food frequency questionnaire (FFQ) at baseline and after 1-year intervention. Cardiometabolic risk markers were measured at both time points. A Mediterranean diet (MedDiet) score was derived from both instruments. Concurrent validity was evaluated by Pearson and intra-class correlation coefficients (ICC) and Bland and Altman limits of agreement. Construct validity was evaluated by assessing 1-year changes in FFQ-reported dietary intake and cardiometabolic profile changes in relation to changes in er-MEDAS. [Results]: A moderate to good correlation between the MedDiet score calculated by both measurement instruments was found: r = 0.61 and ICC = 0.60 (both p < 0.001). Agreement of each of the er-MEDAS items ranged from 55.4% to 85.0% with a moderate mean concordance (kappa = 0.41). Between baseline and 1-year follow-up, energy intake measured by the FFQ decreased by 242 kcal, while Mediterranean food consumption increased in participants with the highest increase in the er-MEDAS MedDiet score. An increase in the er-MEDAS MedDiet score ratings was associated with a decrease in BMI, waist circumference, triglycerides, fasting glucose, diastolic blood pressure, and triglycerides/HDL-cholesterol ratio (p < 0.001 for all), and with an increase in HDL-cholesterol (p = 0.006). [Conclusion]: The er-MEDAS shows a modest to good concurrent validity compared with FFQ data. It shows acceptable construct validity, as a greater er-MEDAS score was associated with more favourable dietary and cardiometabolic profiles over time.The PREDIMED-Plus trial was supported by the official funding agency for biomedical research of the Spanish government, ISCIII through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund four coordinated FIS projects led by Jordi Salas-Salvadó and Josep Vidal, including the following projects: PI13/00673, PI13/ 00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/ 00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/ 00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926; the Special Action Project entitled Implementación y evaluación de una intervención intensiva sobre la actividad física cohorte" PREDIMED-Plus grant to Jordi Salas-Salvadó; the Recercaixa grant to Jordi Salas-Salvadó (2013ACUP00194); the European Research Council Advanced Research Grant 2013–2018 (340918) granted to Miguel Ángel Martínez-Gonzalez, grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013; PS0358/2016, PI0137/2018), the PROMETEO/2017/017 grant from the Generalitat Valenciana, the SEMERGEN grant and FEDER funds (CB06/03) to Josep A. Tur; the Astra Zeneca Young Investigators Award in Category of Obesity and Diabetes 2017 to Dora Romaguera; the ‘FOLIUM’ programme within the FUTURMed project from the Fundación Instituto de Investigación Sanitaria Illes Balears (financed by 2017annual plan of the sustainable tourism tax and at 50% with charge to the ESF Operational Program 2014–2020 of the Balearic Islands). JR17/00022 contract to Olga Castaner from ISCIII. CIBERobn (Centros de Investigación Biomedica en Red: Obesidad y Nutrición), CIBEResp (Centros de Investigación Biomedica en Red: Epidemiología y Salud Publica) and CIBERdem (Centros de Investigación Biomedica en Red: Diabetes y Enfermedades). J. Salas-Salvadó gratefully acknowledges the financial support provided by the ICREA Academia programme. None of the funding sources took part in the design, collection, analysis, or interpretation of the data; in writing the manuscript; or in the decision to submit the manuscript for publication

Incidence and Prediction of Falls in Dementia: A Prospective Study in Older People

Falls are a major cause of morbidity and mortality in dementia, but there have been no prospective studies of risk factors for falling specific to this patient population, and no successful falls intervention/prevention trials. This prospective study aimed to identify modifiable risk factors for falling in older people with mild to moderate dementia.179 participants aged over 65 years were recruited from outpatient clinics in the UK (38 Alzheimer's disease (AD), 32 Vascular dementia (VAD), 30 Dementia with Lewy bodies (DLB), 40 Parkinson's disease with dementia (PDD), 39 healthy controls). A multifactorial assessment of baseline risk factors was performed and fall diaries were completed prospectively for 12 months. Dementia participants experienced nearly 8 times more incident falls (9118/1000 person-years) than controls (1023/1000 person-years; incidence density ratio: 7.58, 3.11-18.5). In dementia, significant univariate predictors of sustaining at least one fall included diagnosis of Lewy body disorder (proportional hazard ratio (HR) adjusted for age and sex: 3.33, 2.11-5.26), and history of falls in the preceding 12 months (HR: 2.52, 1.52-4.17). In multivariate analyses, significant potentially modifiable predictors were symptomatic orthostatic hypotension (HR: 2.13, 1.19-3.80), autonomic symptom score (HR per point 0-36: 1.055, 1.012-1.099), and Cornell depression score (HR per point 0-40: 1.053, 1.01-1.099). Higher levels of physical activity were protective (HR per point 0-9: 0.827, 0.716-0.956).The management of symptomatic orthostatic hypotension, autonomic symptoms and depression, and the encouragement of physical activity may provide the core elements for the most fruitful strategy to reduce falls in people with dementia. Randomised controlled trials to assess such a strategy are a priority