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Fertility and Sterility Jul 2023To date, recurrent implantation failure (RIF) has no clear definition and no clearly identified impaired function. Hence, the term RIF is currently used somewhat... (Review)
Review
IMPORTANCE
To date, recurrent implantation failure (RIF) has no clear definition and no clearly identified impaired function. Hence, the term RIF is currently used somewhat haphazardly, on the basis of clinicians' judgment.
OBJECTIVE
International experts in reproductive medicine met on July 1, 2022, in Lugano, Switzerland, to review the different facets of RIF and define the diagnosis and its appropriate management.
EVIDENCE REVIEW
A systematic review without meta-analysis of studies published in English from January 2015 to May 2022.
FINDINGS
Data indicated that RIF has been largely overevaluated, overdiagnosed, and overtreated without sufficient critical assessment of its true nature. Our analyses show that true RIF is extremely uncommon-occurring in <5% of couples with infertility-and that reassurance and continued conventional therapies are warranted in most cases of assisted reproductive technology (ART) failure. Although the true biologic determinants of RIF may exist in a small subset of people with infertility, they elude the currently available tools for assessment. Without identification of the true underlying etiology(ies), it is reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid blastocyst transfers (or the equivalent number of unscreened embryo transfers, adjusted to the patient's age and corresponding euploidy rate). In addition, other factors should be ruled out that may contribute to her reduced odds of sustained implantation. In such cases, implantation failure should not be the only issue considered in case of ART failure because this may result from multiple other factors that are not necessarily repetitive or persistent. In reality, RIF impacting the probability of further ART success is a very rare occurrence.
CONCLUSION
True RIF is extremely uncommon, occurring in <5% of couples with infertility. Reassurance and continued conventional therapies are warranted in most cases. It would seem reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid embryo transfers (or the equivalent number of unscreened embryos, adjusted to her age).
RELEVANCE
Given the number of internationally recognized experts in the field present at the Lugano meeting 2022, our publication constitutes a consensus statement.
Topics: Humans; Female; Embryo Implantation; Embryo Transfer; Infertility; Reproductive Techniques, Assisted; Aneuploidy; Retrospective Studies
PubMed: 36822566
DOI: 10.1016/j.fertnstert.2023.02.014 -
Particle and Fibre Toxicology Jan 2023Adverse outcome pathways (AOPs) are conceptual frameworks that organize knowledge about biological interactions and toxicity mechanisms. They present a sequence of...
BACKGROUND
Adverse outcome pathways (AOPs) are conceptual frameworks that organize knowledge about biological interactions and toxicity mechanisms. They present a sequence of events commencing with initial interaction(s) of a stressor, which defines the perturbation in a biological system (molecular initiating event, MIE), and a dependent series of key events (KEs), ending with an adverse outcome (AO). AOPs have recently become the subject of intense studies in a view to better understand the mechanisms of nanomaterial (NM) toxicity. Silver nanoparticles (Ag NPs) are one of the most explored nanostructures and are extensively used in various application. This, in turn, has increased the potential for interactions of Ag NPs with environments, and toxicity to human health. The aim of this study was to construct a putative AOPs (pAOP) related to reproductive toxicity of Ag NPs, in order to lay the groundwork for a better comprehension of mechanisms affecting both undesired toxicity (against human cell) and expected toxicity (against microorganisms).
METHODS
PubMed and Scopus were systematically searched for peer-reviewed studies examining reproductive toxicity potential of Ag NPs. The quality of selected studies was assessed through ToxRTool. Eventually, forty-eight studies published between 2005 and 2022 were selected to identify the mechanisms of Ag NPs impact on reproductive function in human male. The biological endpoints, measurements, and results were extracted from these studies. Where possible, endpoints were assigned to a potential KE and an AO using expert judgment. Then, KEs were classified at each major level of biological organization.
RESULTS
We identified the impairment of intracellular SH-containing biomolecules, which are major cellular antioxidants, as a putative MIE, with subsequent KEs defined as ROS accumulation, mitochondrial damage, DNA damage and lipid peroxidation, apoptosis, reduced production of reproductive hormones and reduced quality of sperm. These successive KEs may result in impaired male fertility (AO).
CONCLUSION
This research recapitulates and schematically represents complex literature data gathered from different biological levels and propose a pAOP related to the reproductive toxicity induced by AgNPs. The development of AOPs specific to NMs should be encouraged in order to provide new insights to gain a better understanding of NP toxicity.
Topics: Animals; Male; Humans; Adverse Outcome Pathways; Metal Nanoparticles; Silver; Semen; Genitalia, Male; Mammals
PubMed: 36604752
DOI: 10.1186/s12989-022-00511-9 -
Eye (London, England) Jul 2023Cerebral Visual Impairment (CVI) is a common condition in the UK. Patients with conditions associated with CVI are frequently seen in paediatric ophthalmology clinics... (Review)
Review
Cerebral Visual Impairment (CVI) is a common condition in the UK. Patients with conditions associated with CVI are frequently seen in paediatric ophthalmology clinics offering eye care professionals an opportunity to identify children proactively. In most cases CVI occurs as part of a neurodevelopmental condition or as a feature of multiple and complex disabilities. However, CVI can also be seen in children with apparently typical development. In some cases, high contrast visual acuity is normal and in other cases severely impaired. As such, identification of CVI requires evaluation of aspects of visual performance beyond high contrast acuity and consideration that visual function of those with CVI may fluctuate. Few paediatric ophthalmologists have received formal training in CVI. The detection and diagnosis of CVI varies across the UK and patients report hugely different experiences. A diagnosis of CVI is made based on professional clinical judgement and it is recognised that individual perspectives and local practice in the specific methodologies of assessment will vary. A systematic review and survey of professionals is underway to attempt to reach agreement on diagnostic criteria. Nonetheless, established pathways and published protocols can offer guidance on how a paediatric ophthalmology service can approach assessment of the child with suspected CVI. The purpose of this paper is to present a summary of research and clinical practice methods for detecting and diagnosing CVI in a paediatric ophthalmology outpatient setting. It represents current understanding of the topic and acknowledges the evolving nature of both practice and the evidence-base. A rapid literature review was undertaken to identify articles relating to clinical investigation of children with CVI. A focus group of QTVI and subject matter experts from sight loss charities was undertaken to address areas which were not covered by the literature review.
Topics: Child; Humans; Consensus; Vision Disorders; Visual Acuity; Ophthalmology; Blindness
PubMed: 36258009
DOI: 10.1038/s41433-022-02261-6 -
Annals of Physical and Rehabilitation... Apr 2023Although most research on spatial neglect (SN) has focused on spatial perception deficits with regard to the lateral (left-right) axis, deficits of spatial perception... (Review)
Review
BACKGROUND
Although most research on spatial neglect (SN) has focused on spatial perception deficits with regard to the lateral (left-right) axis, deficits of spatial perception with regard to the vertical (up-down) axis, such as disturbances in the perception of verticality (e.g., judgement of vertical orientations), have also been suggested.
OBJECTIVE
We aimed to systematically analyse reported associations between SN and characteristics of verticality perception while considering the time post-stroke.
METHODS
PubMed, Web of Science, Scopus, PubPsych and PsycArticles databases were searched on May 24, 2022 for articles written in English that evaluated the association between SN and verticality perception (i.e., the subjective visual vertical [SVV], subjective postural vertical [SPV] and subjective haptic vertical [SHV]) in adults after stroke. Left and right SN were considered and had to be assessed using standardized methods. Data were manually extracted, and risk of bias was assessed with the Newcastle-Ottawa Scale. The tilt of the line/chair relative to the gravitational vector and its direction, together with uncertainty (i.e., variability across measurements), were evaluated.
RESULTS
Thirteen studies were included (431 participants after stroke); at least 191 participants exhibited SN. Mainly the first 3 to 6 months post-stroke were evaluated. SN was associated with SVV misperception, which resulted in larger SVV tilts (mostly in the contralesional direction) and uncertainty in participants with than without SN. SVV tilt magnitudes ranged from a mean/median of -8.9° to -2.3° in SN participants and from -1.6° to 0.6° in non-SN participants, the latter falling within normative ranges. For SPV and SHV measurements, the magnitude of tilt and the uncertainty were insufficiently assessed or results were inconclusive.
CONCLUSIONS
SN was associated with larger SVV tilts and uncertainty, which suggests that SVV misperception is a key feature of SN. This observation highlights the importance of regular SVV assessment in people with SN in clinical practice.
PROSPERO
CRD42019127616.
Topics: Adult; Humans; Space Perception; Stroke; Orientation; Perceptual Disorders; Visual Perception
PubMed: 35963568
DOI: 10.1016/j.rehab.2022.101700 -
The Cochrane Database of Systematic... Jun 2022In primary care, general practitioners (GPs) unavoidably reach a clinical judgement about a patient as part of their encounter with patients, and so clinical judgement... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In primary care, general practitioners (GPs) unavoidably reach a clinical judgement about a patient as part of their encounter with patients, and so clinical judgement can be an important part of the diagnostic evaluation. Typically clinical decision making about what to do next for a patient incorporates clinical judgement about the diagnosis with severity of symptoms and patient factors, such as their ideas and expectations for treatment. When evaluating patients for dementia, many GPs report using their own judgement to evaluate cognition, using information that is immediately available at the point of care, to decide whether someone has or does not have dementia, rather than more formal tests.
OBJECTIVES
To determine the diagnostic accuracy of GPs' clinical judgement for diagnosing cognitive impairment and dementia in symptomatic people presenting to primary care. To investigate the heterogeneity of test accuracy in the included studies.
SEARCH METHODS
We searched MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), Web of Science Core Collection (ISI Web of Science), and LILACs (BIREME) on 16 September 2021.
SELECTION CRITERIA
We selected cross-sectional and cohort studies from primary care where clinical judgement was determined by a GP either prospectively (after consulting with a patient who has presented to a specific encounter with the doctor) or retrospectively (based on knowledge of the patient and review of the medical notes, but not relating to a specific encounter with the patient). The target conditions were dementia and cognitive impairment (mild cognitive impairment and dementia) and we included studies with any appropriate reference standard such as the Diagnostic and Statistical Manual of Mental Disorders (DSM), International Classification of Diseases (ICD), aetiological definitions, or expert clinical diagnosis.
DATA COLLECTION AND ANALYSIS
Two review authors screened titles and abstracts for relevant articles and extracted data separately with differences resolved by consensus discussion. We used QUADAS-2 to evaluate the risk of bias and concerns about applicability in each study using anchoring statements. We performed meta-analysis using the bivariate method.
MAIN RESULTS
We identified 18,202 potentially relevant articles, of which 12,427 remained after de-duplication. We assessed 57 full-text articles and extracted data on 11 studies (17 papers), of which 10 studies had quantitative data. We included eight studies in the meta-analysis for the target condition dementia and four studies for the target condition cognitive impairment. Most studies were at low risk of bias as assessed with the QUADAS-2 tool, except for the flow and timing domain where four studies were at high risk of bias, and the reference standard domain where two studies were at high risk of bias. Most studies had low concern about applicability to the review question in all QUADAS-2 domains. Average age ranged from 73 years to 83 years (weighted average 77 years). The percentage of female participants in studies ranged from 47% to 100%. The percentage of people with a final diagnosis of dementia was between 2% and 56% across studies (a weighted average of 21%). For the target condition dementia, in individual studies sensitivity ranged from 34% to 91% and specificity ranged from 58% to 99%. In the meta-analysis for dementia as the target condition, in eight studies in which a total of 826 of 2790 participants had dementia, the summary diagnostic accuracy of clinical judgement of general practitioners was sensitivity 58% (95% confidence interval (CI) 43% to 72%), specificity 89% (95% CI 79% to 95%), positive likelihood ratio 5.3 (95% CI 2.4 to 8.2), and negative likelihood ratio 0.47 (95% CI 0.33 to 0.61). For the target condition cognitive impairment, in individual studies sensitivity ranged from 58% to 97% and specificity ranged from 40% to 88%. The summary diagnostic accuracy of clinical judgement of general practitioners in four studies in which a total of 594 of 1497 participants had cognitive impairment was sensitivity 84% (95% CI 60% to 95%), specificity 73% (95% CI 50% to 88%), positive likelihood ratio 3.1 (95% CI 1.4 to 4.7), and negative likelihood ratio 0.23 (95% CI 0.06 to 0.40). It was impossible to draw firm conclusions in the analysis of heterogeneity because there were small numbers of studies. For specificity we found the data were compatible with studies that used ICD-10, or applied retrospective judgement, had higher reported specificity compared to studies with DSM definitions or using prospective judgement. In contrast for sensitivity, we found studies that used a prospective index test may have had higher sensitivity than studies that used a retrospective index test.
AUTHORS' CONCLUSIONS
Clinical judgement of GPs is more specific than sensitive for the diagnosis of dementia. It would be necessary to use additional tests to confirm the diagnosis for either target condition, or to confirm the absence of the target conditions, but clinical judgement may inform the choice of further testing. Many people who a GP judges as having dementia will have the condition. People with false negative diagnoses are likely to have less severe disease and some could be identified by using more formal testing in people who GPs judge as not having dementia. Some false positives may require similar practical support to those with dementia, but some - such as some people with depression - may suffer delayed intervention for an alternative treatable pathology.
Topics: Aged; Alzheimer Disease; Clinical Reasoning; Cognitive Dysfunction; Cross-Sectional Studies; Dementia; Female; Humans; Physicians, Primary Care; Prospective Studies; Retrospective Studies; Sensitivity and Specificity
PubMed: 35709018
DOI: 10.1002/14651858.CD012558.pub2 -
Patient Preference and Adherence 2021People with disabilities have high rates of chronic health conditions and often require complex medication regimens to manage their health. Approximately 20-50% of... (Review)
Review
People with disabilities have high rates of chronic health conditions and often require complex medication regimens to manage their health. Approximately 20-50% of people with disabilities fail to take their medication as prescribed. It is unclear, however, to what extent the literature describes the effectiveness of medication adherence interventions for people with disabilities. In this review, the inclusion and exclusion criteria of the 182 studies included in the Cochrane Review on Interventions for Enhancing Medication Adherence were evaluated for their inclusion of people with disabilities. Of the studies, 1% excluded persons for hearing impairment, 3% for motor impairment, 7% for visual impairment, and 32% for cognitive impairment. Most studies (65%) did not exclude persons based on specific impairment. Medication event monitoring systems were used in 21% of studies, and investigators excluded people unable to use this device in 5% of studies. Caregiver assistance was an exclusion criteria in 4% of studies. Additional barriers like the ability of investigators to exclude persons based on their judgement were found. These barriers exist in addition to the known barriers affecting persons with disabilities, such as accessibility of research facilities and access to transportation. These data suggest that people with disabilities are systemically excluded from the medication adherence intervention literature. Subsequently, it cannot be assumed that current adherence interventions are effective for people with disabilities. More research is needed to understand how to address medication adherence for people with disabilities.
PubMed: 34345167
DOI: 10.2147/PPA.S314135 -
The Cochrane Database of Systematic... Apr 2021Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric...
BACKGROUND
Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. This is an update of a previously published review.
OBJECTIVES
To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic and non-electronic database searches, handsearches of relevant journals, abstract books and conference proceedings. Both authors double checked the reference lists of the searches Most recent search of the Group's Trials Register: 26 April 2021. On the 26 April 2021 further searches were conducted on the clinicaltrials.gov register to identify any ongoing trials that may be of relevance. The WHO ICTRP database was last searched in 2020 and is not currently available for searching due to the Covid-19 pandemic.
SELECTION CRITERIA
All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment.
DATA COLLECTION AND ANALYSIS
Both authors independently selected trials, assessed trial quality and extracted data.
MAIN RESULTS
The searches identified 40 trials; 17 of these, with 273 participants, were suitable for inclusion, but the number of trials assessing each of the different agents was small. Seven trials were limited to children and four trials enrolled only adults. Meta-analysis was not performed, 14 trials were of a cross-over design and we did not have the appropriate information to conduct comprehensive meta-analyses. All the trials were run in single centres and duration ranged from five days to six months. The included trials were generally not reported adequately enough to allow judgements on risk of bias. However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival.
AUTHORS' CONCLUSIONS
Trials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. Furthermore, due to the unclear risks of bias in the included trials, we are unable to make firm conclusions based on the evidence reported therein. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.
Topics: Abdominal Pain; Adult; Child; Cystic Fibrosis; Dietary Fats; Gastric Acid; Gastrointestinal Agents; Histamine H2 Antagonists; Humans; Intestinal Absorption; Pancreas; Proton Pump Inhibitors; Randomized Controlled Trials as Topic
PubMed: 33905540
DOI: 10.1002/14651858.CD003424.pub5 -
Journal of Clinical Medicine Feb 2021There is increasing interest in the use of technology to support social health in dementia. The primary objective of this systematic review was to synthesize evidence of... (Review)
Review
There is increasing interest in the use of technology to support social health in dementia. The primary objective of this systematic review was to synthesize evidence of effectiveness of digital technologies used by people with dementia to improve self-management and social participation. Records published from 1 January 2007 to 9 April 2020 were identified from Pubmed, PsycInfo, Web of Science, CINAHL, and the Cochrane Central Register of Controlled Trials. Controlled interventional studies evaluating interventions based on any digital technology were included if: primary users of the technology had dementia or mild cognitive impairment (MCI); and the study reported outcomes relevant to self-management or social participation. Studies were clustered by population, intervention, and outcomes, and narrative synthesis was undertaken. Of 1394 records identified, nine met the inclusion criteria: two were deemed to be of poor methodological quality, six of fair quality, and one of good quality. Three clusters of technologies were identified: virtual reality, wearables, and software applications. We identified weak evidence that digital technologies may provide less benefit to people with dementia than people with MCI. Future research should address the methodological limitations and narrow scope of existing work. In the absence of strong evidence, clinicians and caregivers must use their judgement to appraise available technologies on a case-by-case basis.
PubMed: 33562749
DOI: 10.3390/jcm10040604 -
Aging and Disease Jul 2020The SARS-CoV-2 tendency to affect the older individuals more severely, raises the need for a concise summary isolating this age population. Analysis of clinical features... (Review)
Review
The SARS-CoV-2 tendency to affect the older individuals more severely, raises the need for a concise summary isolating this age population. Analysis of clinical features in light of most recently published data allows for improved understanding, and better clinical judgement. A thorough search was performed to collect all articles published from 1st of January to 1st of June 2020, using the keywords and followed by the generic terms , or . The quality assessment of studies and findings was performed by an adaptation of the STROBE statement and CERQual approach. Excluding duplicates, a total of 1598 articles were screened, of which 20 studies were included in the final analysis, pertaining to 4965 older COVID-19 patients (≥60 years old). Variety in symptoms was observed, with fever, cough, dyspnea, fatigue, or sputum production being the most common. Prominent changes in laboratory findings consistently indicated lymphopenia and inflammation and in some cases organ damage. Radiological examination reveals ground glass opacities with occasional consolidations, bilaterally, with a possible peripheral tendency. An evident fraction of the elderly population (25.7%) developed renal injury or impairment as a complication. Roughly 71.4% of the older adults require supplementary oxygen, while invasive mechanical ventilation was required in almost a third of the reported hospitalized older individuals. In this review, death occurred in 20.0% of total patients with a recorded outcome (907/4531). Variability in confidence of findings is documented. Variety in symptom presentation is to be expected, and abnormalities in laboratory findings are present. Risk for mortality is evident, and attention to the need for supplementary oxygen and possible mechanical ventilation is advised. Further data is required isolating this age population. Presented literature may allow for the construction of better predictive models of COVID-19 in older populations.
PubMed: 32765959
DOI: 10.14336/AD.2020.0620 -
Surgery Aug 2020Surgical patients incur preventable harm from cognitive and judgment errors made under time constraints and uncertainty regarding patients' diagnoses and predicted...
BACKGROUND
Surgical patients incur preventable harm from cognitive and judgment errors made under time constraints and uncertainty regarding patients' diagnoses and predicted response to treatment. Decision analysis and techniques of reinforcement learning theoretically can mitigate these challenges but are poorly understood and rarely used clinically. This review seeks to promote an understanding of decision analysis and reinforcement learning by describing their use in the context of surgical decision-making.
METHODS
Cochrane, EMBASE, and PubMed databases were searched from their inception to June 2019. Included were 41 articles about cognitive and diagnostic errors, decision-making, decision analysis, and machine-learning. The articles were assimilated into relevant categories according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.
RESULTS
Requirements for time-consuming manual data entry and crude representations of individual patients and clinical context compromise many traditional decision-support tools. Decision analysis methods for calculating probability thresholds can inform population-based recommendations that jointly consider risks, benefits, costs, and patient values but lack precision for individual patient-centered decisions. Reinforcement learning, a machine-learning method that mimics human learning, can use a large set of patient-specific input data to identify actions yielding the greatest probability of achieving a goal. This methodology follows a sequence of events with uncertain conditions, offering potential advantages for personalized, patient-centered decision-making. Clinical application would require secure integration of multiple data sources and attention to ethical considerations regarding liability for errors and individual patient preferences.
CONCLUSION
Traditional decision-support tools are ill-equipped to accommodate time constraints and uncertainty regarding diagnoses and the predicted response to treatment, both of which often impair surgical decision-making. Decision analysis and reinforcement learning have the potential to play complementary roles in delivering high-value surgical care through sound judgment and optimal decision-making.
Topics: Attitude to Health; Clinical Decision-Making; Decision Making, Shared; Decision Support Techniques; Decision Trees; Electronic Health Records; Humans; Machine Learning; Numbers Needed To Treat; Patient Preference; Patient-Centered Care; Surgical Procedures, Operative
PubMed: 32540036
DOI: 10.1016/j.surg.2020.04.049